Author: Dr. Sanja Fitzgerald
Single-Arm Trial? Make Sure it Can Support More Than Regulatory Approval.
27 July 2026
Single-arm trials remain one of the most polarizing topics in drug development.
Critics argue they lack comparative evidence. Sponsors argue that randomization was ethically or practically impossible—often falling back on the simple rationale that no approved therapy exists for the indication. HTA bodies question the resulting uncertainty. Regulatory authorities ultimately authorize the medicines.
The most important question to answer is:
Could this trial reasonably have had a comparator?
And "comparator" does not necessarily mean an approved disease-modifying therapy. It may include standard supportive care, procedural controls, placebo, or best supportive management.
The existence of a standard of care does not automatically mean it is an appropriate comparator.
The answer to that question determines whether a single-arm trial represents poor study design—or the best evidence that could ethically and scientifically have been generated.
Ethics and Feasibility Dictate Trial Design—Not Reimbursement
By the time a reimbursement dossier reaches an HTA body, the clinical trial design was fixed years earlier, guided by scientific advice, ethics committees, and regulatory frameworks.
The decision to randomize is primarily an ethical and scientific choice—not a pricing strategy.
A comparator arm is not merely an approved drug. A valid comparator requires a context of clinical equipoise—genuine uncertainty regarding which intervention is superior. If early data suggest a transformative treatment effect in a rapidly fatal condition, forcing randomization against supportive care presents profound ethical barriers.
This is particularly evident in severe pediatric diseases, where trials do not evaluate two incremental therapeutic options, but rather an intervention against progressive, irreversible functional loss. Judging evidence without accounting for these ethical constraints expects trialists to meet standards that were never realistically achievable.
Rarity Alone Does Not Justify a Single-Arm Design
Rare disease status is frequently cited as automatic justification for a single-arm trial.
It is not.
The absence of an approved drug is equally insufficient on its own.
Many rare conditions can—and should—be studied through randomized controlled trials using supportive care, placebo, or procedural controls where appropriate.
The decision depends on a combination of factors:
- Disease natural history and predictability
- Rate of disease progression and severity
- Magnitude of the expected treatment effect
- Feasibility of recruitment and population heterogeneity
- Availability of established, validated historical cohorts
Ultra-rare prevalence alone does not eliminate the need for comparative evidence.
Conversely, certain disease settings render randomization ethically or practically impossible regardless of patient numbers.
The Evolution of Evidence: SMA as an Example
The development history of spinal muscular atrophy (SMA) illustrates how evidence generation requirements evolve as treatment paradigms change.
When Spinraza (nusinersen) was evaluated in infants with Type 1 SMA, no disease-modifying therapy existed. Rather than defaulting to a single-arm study, the pivotal ENDEAR trial used a sham-procedure control alongside standard supportive care. This design preserved blinding and generated rigorous comparative evidence while addressing ethical concerns through pre-specified interim analyses allowing early termination once efficacy became clear.
When Zolgensma (onasemnogene abeparvovec) entered clinical development, an active treatment—Spinraza—was already available. Nevertheless, the pivotal STR1VE study was conducted as an open-label, single-arm trial compared with a well-characterized natural history cohort.
Why was a single-arm study considered acceptable despite the existence of an approved alternative?
Because trial design depended on multiple concurrent factors:
- The nature of the intervention: a one-time gene therapy versus chronic intrathecal administration.
- A highly predictable natural history in untreated Type 1 SMA.
- An early efficacy signal suggesting a transformative—not incremental—treatment effect.
- A narrowly defined patient population in which recruitment into a randomized comparison would have been exceptionally difficult.
Together, these factors made historical controls scientifically and ethically acceptable for regulatory decision-making.
However, while sufficient for market authorization, important uncertainties regarding comparative effectiveness, long-term treatment positioning, and durability remained after approval—precisely the uncertainties that later became highly relevant for HTA and post-marketing evidence generation.
Regulatory Approval and HTA Answer Different Questions
Regulators and HTA bodies evaluate the same clinical evidence to answer fundamentally different questions.
Regulators ask:
Does the evidence demonstrate a positive benefit-risk profile in the intended patient population?
HTA bodies ask:
Is the comparative evidence sufficient to justify the requested price relative to existing therapeutic alternatives over the long term?
Neither perspective is incorrect.
They simply operate under different tolerances for uncertainty.
Zolgensma Explains Why
Zolgensma launched with a list price of $2.125 million, justified by the prospect of lifelong benefit following a single infusion.
At launch, no clinical trial could demonstrate 10- or 20-year durability.
Subsequent long-term follow-up studies and real-world evidence have generally supported sustained clinical benefit for many treated children. At the same time, clinical practice has revealed more complex treatment pathways than initially anticipated, with some patients subsequently receiving nusinersen or risdiplam as combination or sequential therapy.
This does not invalidate the original regulatory approval.
Nor does it suggest the therapy failed.
It highlights the fundamental distinction between regulatory and HTA decision-making.
Regulatory evaluation assesses efficacy and safety based on the evidence available at the time of authorization.
HTA evaluates whether the assumptions underpinning a multi-million-dollar reimbursement decision—durability, comparative value, future treatment requirements, and lifetime cost-effectiveness—are sufficiently certain.
HTA was never assessing only the clinical trial.
It was assessing the uncertainty surrounding the value proposition.
Managing Uncertainty Rather Than Rejecting Evidence
A single-arm trial can be methodologically sufficient for regulatory approval while leaving residual uncertainty that challenges conventional HTA assessments.
These conclusions are not contradictory.
They reflect different decisions.
Increasingly, HTA systems address this through managed entry agreements (MEAs), including outcomes-based arrangements, conditional reimbursement, and mandatory post-launch registries. Rather than ignoring uncertainty, manufacturers and payers explicitly agree on how it will be managed while patients gain access and additional evidence is generated.
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The challenge is rarely the single-arm trial itself.
The challenge is asking a single clinical trial to answer long-term comparative, economic, and durability questions it was never designed to answer.
Pharma is Leaving Europe. But US Price Reductions Will Continue.
9 July 2026
Over the past year, several pharmaceutical companies have delayed launches, withdrawn products, or walked away from reimbursement negotiations across Europe. The rationale is familiar: avoid establishing low public prices that could erode global value through international reference pricing (IRP).
It is a strategy that has shaped launch sequencing for decades.
The problem is that the commercial environment has changed.
Today, the biggest threat to US pharmaceutical pricing is no longer a reimbursement decision in France, Denmark, or Switzerland. It is US legislation.
Europe Is Still Being Managed Like It Sets Global Prices
Recent examples illustrate the industry's continued reliance on traditional IRP defence.
· France: Pfizer signalled that supplying products at government-imposed prices could become commercially unsustainable.
· Denmark: Amgen withdrew Repatha after reimbursement negotiations resulted in significant pricing pressure.
· Switzerland: Roche removed Lunsumio from the Specialities List after negotiations with the Federal Office of Public Health (BAG) failed, opting for a non-public access pathway rather than establishing a publicly referenced reimbursement price.
These decisions differ operationally, but they pursue the same objective: prevent low published prices from becoming reference points in other markets.
For many years, this was commercially rational.
Whether it remains sufficient is another question.
The Centre of Pricing Power Has Shifted
The Inflation Reduction Act fundamentally altered the pricing landscape.
For the first time, manufacturers face a statutory mechanism that systematically reduces prices for selected high-expenditure medicines through Medicare negotiation. The programme expands annually, creating a predictable pathway for long-term price compression that operates independently of European launch sequencing.
At the same time, ongoing policy discussions around international reference pricing—including Most Favoured Nation (MFN)-style frameworks—demonstrate that US policymakers are increasingly willing to combine domestic pricing reform with international benchmarking.
The important point is not which policy ultimately dominates.
It is that the direction of travel has changed.
US pharmaceutical pricing is increasingly being determined by domestic policy rather than by whether another European country enters an external reference basket.
Why Higher Swiss Prices Won't Change the Equation
Switzerland is often viewed as a strategic market because it maintains some of Europe's highest medicine prices.
That has led to proposals that increasing Swiss reimbursement levels—or introducing supplementary innovation funding—could strengthen international pricing benchmarks.
The evidence suggests otherwise.
Swiss prices are already among the highest within OECD reference baskets. Since many international reference pricing systems benchmark against lower-priced countries—or the second-lowest price—Switzerland rarely determines the reference value.
Increasing one of the highest prices in the basket does little to influence the benchmark that actually matters.
The Bigger Strategic Risk
Many companies continue to optimise for a pricing environment that is gradually disappearing.
International reference pricing remains an important consideration. It will continue to influence launch sequencing, portfolio planning, and reimbursement strategy.
But it is no longer the dominant force shaping long-term US revenues.
The larger challenge is adapting to an environment where domestic legislation increasingly determines commercial outcomes.
That changes the strategic calculus.
Withdrawing from European markets may protect against marginal reference pricing effects, but it also forfeits revenue, delays patient access, weakens stakeholder relationships, and reduces real-world evidence generation. Those trade-offs become harder to justify if the primary drivers of US price erosion lie elsewhere.
Market Access Needs a New Playbook
The industry has spent years refining strategies to defend value against international reference pricing.
The next decade will demand something different.
Success will depend less on preventing another low European price and more on anticipating how US legislation, payer behaviour, and value-based contracting reshape global commercial strategy.
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The question is no longer whether companies should defend international pricing.
The question is whether they are defending the right risk.
The First JCA Report: When the Framework Sets an Impossible Task
19 June 2026
Last week in Istanbul at the HTAi Annual Meeting, the first published EU JCA report was presented. The manufacturer welcomed it publicly. Parts of the rare disease community cited it as proof the framework is broken for rare paediatric oncology.
Having read the dossier and heard the reactions on the ground, here is my five cents: Ipsen's evidence generation was largely done right. The trap was the framework.
What the Evidence Landscape Offered
Tovorafenib received EMA conditional MA in April 2026 for relapsed/refractory paediatric LGG with BRAF alteration after ≥1 prior systemic therapy. FIREFLY-1 was a single-arm Phase 2 trial — the expected design for an indication with no standardised second-line treatment.
Before submission, Ipsen did the right things. The SLR confirmed no comparative data existed for ~75% of the trial population (BRAF fusions/rearrangements). An RWE feasibility study was conducted — one US database was explored, deemed unsuitable (insufficient R/R patients with BRAF alterations, inadequate follow-up), and the conclusion was correctly documented: no fit-for-purpose external control existed. And even if US RWE had been feasible, IQWiG's documented position is that US real-world data does not transfer to the EU healthcare context.
The honest conclusion from all three exercises was that comparative evidence did not exist. That is the evidence environment, not a submission failure.
The Structural Trap
The HTACG assigned 8 PICOs. Six had no comparative data anywhere — not because Ipsen failed to generate it, but because the disease landscape has none. Conditional MA was the right decision for patients. But it is a JCA liability: EMA says the evidence base is incomplete and approves anyway; JCA asks for comparative evidence to determine added therapeutic value. These point in opposite directions. For six PICOs the framework documented the gap and moved on.
For PICO 5 — the BRAF V600E subpopulation (~22 patients in FIREFLY-1) — a comparator study existed: Bouffet 2023, R/R dabrafenib+trametinib in BRAF V600 LGG, n=36. Ipsen attempted an unanchored MAIC. That was the wrong call.
The mathematics make this clear. Arm 1 had 13 V600E patients. After weighting: ESS = 5.82. Fewer than six effective patients. Had both arms been included (22 patients), Scenario 1 shows ESS = 11.54 — still far below the minimum for meaningful inference on PFS in oncology (50–100 events). There was also a baked-in endpoint incompatibility: Bouffet 2023 used modified RANO-HGG criteria (Minor Responses excluded); FIREFLY-1 used full RANO-LGG (Minor Responses included). This is a field-level problem from pre-harmonisation trial design — not Ipsen's fault, but it made any response rate comparison structurally invalid.
The correct response to PICO 5 was the same response given to the other six: declare infeasible, document the reasons — subgroup too small for MAIC inference, positivity assumption unverifiable, endpoint frameworks incompatible — and present FIREFLY-1 data transparently as single-arm evidence.
What Went Wrong
Instead, the comparison was attempted. And the execution gave assessors additional reasons to document conduct failures. Arm 2 efficacy data was withheld (halving the matching population and driving ESS from 11.54 to 5.82). Investigator-assessed PFS from Bouffet 2023 was omitted, flagged as selective reporting. The 3-year data cut (May 2025) was not database-locked when the JCA opened (June 2025) — a planning failure, not deliberate withholding, but the result was data assessors could not validate. The formal clarification meeting produced no minutes and no clear answers.
What the Framework Must Learn
The Regulation does not yet have implemented rare disease proportionality provisions. Eight PICOs applied to a heterogeneous ultra-rare paediatric indication where the mathematics of comparative assessment could not be satisfied is the framework operating at full specification against an evidence environment that cannot support it.
The fix is a feasibility gate before PICO assignment: check whether the mathematical preconditions for indirect comparison exist — sufficient populations, comparable endpoints, verifiable positivity — before asking the developer to produce evidence for them. If they fail, redesign the PICO. This case should be the precedent that drives that change.
THE CORE TAKEAWAY
The first JCA report is not a verdict on a developer. It is a collision between a framework built for comparative evidence and an indication where that evidence cannot exist — and neither side had a clear protocol for how to handle it.
Ipsen's error was not the evidence generation. It was attempting a comparison that the mathematics could never support, and executing it in a way that created an additional conduct record alongside the statistical failure.
The lesson for developers in the JCA pipeline is not to generate more comparative data. It is to know when declaring a comparison infeasible is the stronger position — and to make that argument proactively, with the structured rationale ready before assessors find it themselves.
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KNOW WHEN NOT TO ATTEMPT THE COMPARISON. THAT IS THE ARCHITECTURE.
Navigating this unyielding framework requires a specialized architectural bridge. At Sur Access, we tailor-make your JCA strategy and run predictive PICO simulations—ensuring your clinical evidence is insulated against biostatistical audits, whether you are launching a conventional oncology blockbuster or an ultra-rare orphan technology.
Partner with an expert who has been in the room. Secure your JCA-ready edge at www.sur-access.com.
Swiss Market Access: Provisional Access, Real-world Evidence, and the New Economic Reality
5 June 2026
For years, the Swiss market access narrative has been dominated by debates over transparency and International Reference Price (IRP) spillover. With the implementation of the Cost Containment Package 2 (CPP2) anticipated in early 2027, the Swiss Federal Office of Public Health (BAG) is shifting its approach.
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The new framework introduces a pragmatic solution: provisional reimbursement from "Day 0."
Swiss healthcare legislation is moving toward a patient-first access architecture. By allowing reimbursement from the date of Swissmedic marketing authorization, the BAG is effectively reducing the administrative access lag that previously delayed patient availability while waiting for final Specialities List (SL) listing.
1. "Reimbursement Zero": Access as a Default
Under CPP2, the BAG integrates flexible pricing and evidence-based models into its negotiation scheme:
· The Benefit: Patients gain immediate access to innovation at a provisional, legally defined price. This represents a significant improvement for therapies addressing high unmet needs.
· The Evidence Loop: During the up to 24-month provisional window, the transition to final listing is not merely a bureaucratic process. The BAG may require manufacturers to address uncertainties regarding the therapeutic benefit or economic efficiency. While this often involves collecting Real-World Evidence (RWE) to bridge gaps between clinical trial data and clinical reality, the final price setting remains anchored in the statutory assessment criteria (effectiveness, appropriateness, and economic efficiency). It is a move toward more evidence-based decision-making.
2. Confidentiality: A Strategic Necessity for Patient Access
The shift toward confidential pricing is a functional necessity for the Swiss market.
· Why it happened: In an era of aggressive IRP and emerging Most Favored Nation (MFN) policies globally, transparent "net" prices in Switzerland often created downward pressure on prices in other jurisdictions.
· The "Win-Win": Confidentiality allows the BAG to secure a price that is sustainable for the Swiss healthcare budget while enabling manufacturers to protect their global pricing structures from IRP-driven erosion. This helps ensure that Switzerland remains an attractive launch market for innovative global biotechs.
3. MEAs: Asset-Specific, Not Industry-Wide
Unlike the collective "tax-and-clawback" models seen in other European markets, the Swiss approach is surgical. Managed Entry Agreements (MEAs) under CPP2 are asset-specific.
· Strategic Responsibility: This places the responsibility on the manufacturer to design an access model that fits the asset’s specific clinical and economic profile.
· Collaborative Path: The BAG is moving toward a framework where manufacturers demonstrate the value and evidence of their asset, allowing for the structuring of sustainable, long-term reimbursement pathways.
THE CORE TAKEAWAY
The Swiss system is evolving into an increasingly evidence-based marketplace.
Swiss access is no longer a static submission process. It is now a dynamic evidence-generation lifecycle. Companies that thrive under CPP2 will be those that move beyond simple dossier submission to architect a pathway that integrates robust data collection, strategic MEAs, and a sophisticated understanding of the IRP/MFN landscape.
The BAG is not looking for a "tax revenue stream." They are seeking clinical partners who can demonstrate the real-world value of their innovation within the established statutory framework.
Swiss Market Access for Narcotics
20 May 2026
Evaluating the pathways for controlled substances—specifically medical narcotics—reveals a unique set of strategic access and regulatory hurdles. For years, the industry viewed the market access of heavily restricted substances as a marginal regulatory sub-specialty. However, with the evolution of medical cannabis, specialized opioid agonist therapies (OAT), and emerging clinical psychedelic frameworks, narcotics have entered first-tier therapeutic conversations.
Today, extreme narcotics like medical heroin can achieve marketing authorization (MA) or formal reimbursement. In Switzerland, pharmaceutical-grade heroin (diacetylmorphine) was granted a formal Swissmedic MA and added to the Specialities List (SL) under the brand Diaphin® to treat refractory opioid dependence.
The formal entry for Diaphin® on the Swiss SL explicitly reflects these rigid operational boundaries through its strict limitation (Limitatio). Navigating patient access for these highly sensitive compounds requires a sophisticated understanding of localized, individualized access architecture.
1. The Swiss Narcotics Landscape: Highly Regulated Efficacy
Controlled substances are medically integrated within Swiss clinical frameworks for specific, severe therapeutic indications:
· Severe Pain Management & Palliative Care: High-potency opioids (morphine, oxycodone, fentanyl, hydromorphone).
· Neuropsychiatric Disorders: CNS stimulants (methylphenidate, dexamphetamine) for ADHD and narcolepsy.
· Opioid Agonist Therapy (OAT): Specialized regimens including methadone, buprenorphine, and diacetylmorphine.
· Severe Spasticity: Standardized THC and CBD medical cannabis formulations.
· Treatment-Resistant Psychiatric Conditions: Emerging individual exception frameworks for psychedelic substances (MDMA, psilocybin) targeting refractory PTSD and depression.
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2. The Early Access Vehicle: Article 71a–71d KVV
What happens if a manufacturer has a narcotic or controlled psychotropic substance that does not yet hold a Swissmedic MA or an SL listing? The entry sequence skips the standard commercial pricing process and leverages the name-based individual exception framework:
· Individual Case Reimbursement: A treating physician submits a formal name-based request to a patient's health insurer for a drug that is used off-label or is registered but not yet on the SL.
· The Clinical Hurdle: The insurer’s medical advisor must verify that the disease is fatal or chronically severe, no listed alternative exists, and the therapy expects a high individual clinical benefit.
· Bypassing the FOPH Price Caps: This mechanism operates outside the centralized FOPH pricing process, protecting the asset from a standard public TQV/APV calculation setting a premature broad market ceiling price.
3. Direct Negotiation: Pricing Mechanics Under Article 71 KVV
Because Article 71 KVV bypasses the standard, mathematically weighted 50/50 External Price Comparison (APV) and Therapeutic Cross-Comparison (TQV) formula, pricing is determined through decentralized, bilateral negotiations directly with individual insurers or their purchasing associations. This model follows a strict value-and-benefit logic:
· The Benefit-Based Rebate Grid: Insurers rely on standardized clinical assessment frameworks (OLU-Tools) to grade the therapy's value. A high documented benefit allows the manufacturer to maintain a price near their target, while moderate or poorly documented utility triggers steep, mandatory rebate tiers.
· The "Wirtschaftlichkeit" Benchmark: If the substance is already listed on the SL for another primary indication but is requested off-label under Article 71a, the FOPH's confidential "economic price" (wirtschaftlicher Preis) serves as the absolute baseline, ensuring insurers do not pay a premium above existing state-negotiated net prices.
· The High-Stakes Stalemate: Because each insurer holds individual veto power over the economic viability of the request, failing to agree on a proportional rebate means the insurer is legally blocked from granting coverage, and the request is rejected as "uneconomical".
๐ฅ THE CORE TAKEAWAY
The Swiss access framework for medical narcotics is highly pragmatic, shifting from strictly managed standard list inclusions like Diaphin® to specialized name-based reimbursement for unregistered assets. Ignoring the specific legal nuances of pathways like Article 71 KVV is a direct risk to your asset's global valuation. Stop speculating and start architecting your global evidence.
The China Pivot
6 May 2026
A Shift in Global Strategy
As a Swiss-based Market Access expert, my focus is typically the European landscape and the complexities of the Joint Clinical Assessment (JCA). However, attending Swiss Biotech Day 2026 in Basel this week provided a necessary reality check. The energy at the event was focused on a clear shift in international strategy.
For years, the industry viewed China as a secondary market or a source of low-cost manufacturing. That era is over. China has emerged as a first-tier market that must be integrated into your launch sequence from the first day. If you do not plan your China strategy today, you are neglecting a significant portion of your global valuation. The relationship between Switzerland and China has moved beyond simple transactions to a model of cross-border startups and full-exchange partnerships based on high-level expertise rather than price.
- The Swiss-Chinese Partnership: Deep Integration
This collaboration is a sustainable partnership that goes beyond simple transactions.
- Government Level Support: This collaboration is supported at high levels to foster trust and cultural understanding between the two ecosystems.
- The Dual-Incorporation Model: There is a surge in startups being incorporated simultaneously in Switzerland, Hong Kong, and Mainland China.
- Cross-Border Exchange: Startups are being formed with a full exchange of data and leadership across these borders.
- Strategic Proximity: Partners are staying close to each other to understand local business culture and build long-term trust.
2. Why the Pivot? The EU Stalling Effect
Market Access in Europe is becoming more difficult due to the JCA and Most Favored Nation (MFN) logic in the US. Many companies are intentionally delaying European launches to protect their US price floor.
- The Revenue Gap: Delaying a launch in Europe creates a significant revenue deficit in the early years of a drugs lifecycle.
- The China Solution: Companies are now orienting toward China to provide the patient volume and data needed to support their global valuations.
- Evidence Generation: China provides an environment to gather evidence that can support global clinical dossiers while European assessments are pending.
3. The Statutory Framework: The NRDL
The National Reimbursement Drug List (NRDL) is the primary mechanism for market access in China.
- Government Control: This list is managed by the National Healthcare Security Administration (NHSA) and determines which medicines are covered by basic medical insurance.
- The Negotiation: Entry requires a rigorous negotiation process where partners are chosen based on capability and expertise rather than just the lowest price.
- Pricing Dynamics: Changes in domestic pharmaceutical pricing in China are expected to shift international dynamics soon, making global coordination essential.
4. The Private Insurance Sector: The Secondary Market
The Private Health Insurance (PHI) market is where premium innovation can gain traction outside of the government list.
- Patient Volume: Over 100 million people now have supplemental private insurance, such as city-level Huiminbao plans.
- The Opportunity: For US, Swiss, and EU companies, the private market is a faster entry point to reach patients who want international standards of care before a drug is listed on the NRDL.
- Innovative Catalogues: In January 2026, a dedicated innovative drug catalogue -Commercial Healthcare Insurance Innovative Drug Catalogue (CHIIDL) - was launched for the commercial insurance market to speed up access. This catalogue acts as a secondary market for high-value innovative drugs that may not yet be on the NRDL, allowing commercial insurers to decide on coverage for premium therapies.
5. Health Technology Assessment (HTA) and Pricing Potential
China has professionalized its access landscape. It is no longer a black box for Western companies.
- HTA Rigor: The system has transitioned from a focus on budget impact to sophisticated Cost-Effectiveness Analysis (CEA).
- Global Referencing: The NHSA monitors international pricing and clinical value. Your HTA outcomes in Europe or the US will impact your Chinese negotiation.
- Pricing Comparison: While China was a low-price market, it now rewards clinical value. Prices remain lower than in the US but are increasingly competitive with European net prices.
- The NRDL Anchor: NRDL prices are often 50% to 70% lower than US list prices, but they provide immediate access to 1.4 billion people.
Can an EU Expert Prepare You for China?
I am an expert in the JCA and European & Swiss Market Access. I am not a China-specific access consultant. However, as an Access Architect, my role is to ensure your clinical data is strong enough to survive any HTA—whether in Berlin, Paris, Bern or Beijing.
If your Clinical Development Plan only looks at Western comparators, you are failing the China test. You do not need me to file your Chinese dossier; you need me to ensure your global evidence package does not fail when it reaches the Chinese border.
๐ฅ THE CORE TAKEAWAY
The Swiss-Chinese biotech relationship is a mature, high-level ecosystem. In 2026, ignoring China is a risk to your global rNPV. Stop speculating and start architecting your global evidence.
Why Revolution Medicines Needs a Successful European Launch to Support its $30B Valuation
14 April 2026
The biotech world is buzzing today. Revolution Medicines (RVMD) just released updated data for their RASON multi-selective inhibitor, daraxonrasib (RMC-6236). The numbers are, quite frankly, transformative: doubling overall survival (OS) in second-line pancreatic cancer with a Hazard Ratio of 0.40.
The stock is surging toward a $30 billion valuation.
But if you are an investor or a C-suite executive looking at these results, you shouldn't just be looking at the clinical "waterfall" plots. You should be looking at the PICO Shadow in Europe.
At Sur Access, I’ve modeled the rNPV for this asset, and the conclusion is clear: The $30 billion valuation isn’t just built on US potential—it is anchored in Berlin.
1. The "Bucket" Trap: Surviving the JCA Comparator
The registrational trial for RMC-6236 compared the drug against a "bucket" of investigator’s choice chemotherapies. In the old days of Market Access, this was a risky move. Under the new Joint Clinical Assessment (JCA) rules, if your comparator doesn't match the "Standard of Care" in every member state, you risk a "No Added Benefit" rating.
However, when you double survival (13.2 months vs 6.7 months), the "bucket" is no longer your access hurdle.
- The Sur Access Insight: A Hazard Ratio of 0.40 is the "Gold Standard" for a Considerable Benefit rating. This rating is the mechanical trigger that allows a manufacturer to break away from "generic chemo pricing" and claim a premium innovation price.
2. The US Net Price is a "German Shadow"
In my latest rNPV modeling for daraxonrasib, I looked at the "No Europe" scenario. Many boards think: "The German comparators are cheap generics; let’s skip it to protect our US List Price."
This can be a $10 billion mistake.
Under the current Most Favored Nation (MFN) and GLOBE pricing models in the US, the U.S. Net price is increasingly a mathematical derivative of European net prices.
- The Reality: Launching in Germany with a "Considerable Benefit" rating sets a high price anchor (approx. €140k+).
- The Domino: Because the U.S. Net price in 2026 often tracks at ~120% of the German Net, a win in Berlin guarantees a global price floor.
- The Risk: If you don't launch in Germany, the U.S. price is left "unanchored," making it vulnerable to the most aggressive international benchmarks (like Australia or lower-tier OECD markets).
3. The "Considerable" Difference: Binary Valuation
If daraxonrasib were to receive a "Minor Benefit" rating, the global rNPV would contract by billions. Why? Because a "Minor" rating in Germany would trigger a price "ratchet" across France, Italy, and Spain, which then reflects back into the U.S. via International Reference Pricing.
Revolution Medicines is currently a $30B company because the market is betting on a Considerable Benefit rating. The clinical data supports it, but the Access Architecture—how that data is presented to the JCA—will determine if that value is captured or lost.
4. Why "Wait and See" is Valuation Decay
For assets like RMC-6236, Europe isn't just "extra revenue." It is valuation insurance.
1. The Volume: 20-25% of global revenue.
2. The Price Floor: The German "Considerable" rating prevents the US Net price from sliding toward the generic baseline.
3. The Evidence: The Real-World Evidence (RWE) gathered in Europe will be the primary weapon used to defend the drug’s price when it eventually hits the CMS negotiation table in Washington.
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๐ฅ THE ULTIMATE TAKEAWAY: Revolution Medicines is the perfect case study for the Payer-Ready rNPV. You cannot value a US biotech asset today without a "Deep Dive" into the EU JCA PICO requirements.
Standard rNPV models are insufficient for this analysis. You must use a payer-ready model that directly links the German G-BA outcome to the U.S. Net price. Without this connection, the model reflects unrealistic expectations rather than actual market conditions.
The Domino Effect—Why Skipping Europe is a Strategic Trap
7 April 2026
There is a dangerous conversation happening in biotech boardrooms right now. Because of the Joint Clinical Assessment (JCA), many companies—both US-based (like Insmed) and European (like Bayer)—are quietly deferring or even canceling their European launches. They believe that by staying out of Europe, they can "protect" their high US prices from international benchmarking.
Not quite so. This isn't just about future launches; it is a domino effect that is already hitting drugs that have been on the market for over a decade.
1. The Backtrack: CMS is Negotiating the Past, Not Just the Future
Investors often think they only need to worry about the "JCA Haircut" for new assets. But the Inflation Reduction Act (IRA) is designed to catch up with the past.
- The Reality: CMS is currently negotiating prices for some of the world’s biggest drugs that launched years ago, including Eliquis, Enbrel, and Januvia.
- The 2026 Shock: These older drugs saw price reductions of 38% to 60% below their 2023 list prices starting January 1, 2026.
- The Lesson: Avoiding a European launch today does not protect you from CMS lowering your price tomorrow. The "contamination" is retroactive.
2. These Aren't "Show Prices"—They are Real Savings
People often think "negotiated prices" are just a new version of the list price. They are real price reductions. These cuts represent a massive shift in the actual money flowing from Medicare to manufacturers.
- Round 1 (10 Drugs): CMS estimated that if these prices had been in effect in 2023, Medicare would have saved $6 billion, representing a 22% net saving relative to the already-discounted prices plans were paying.
- Round 2 (15 Drugs): For the second group, including popular GLP-1s like Ozempic and Wegovy, CMS estimated even deeper savings of $12 billion—a 44% net saving.
- Total Impact: To date, the drugs selected for negotiation account for $125 billion—more than one-third of all Medicare drug spending.
3. The "GLOBE" and MFN Reality: No Place to Hide
If you think you can hide your "Net Price" by staying in the US, you haven't seen the GLOBE (Global Benchmark for Efficient Drug Pricing) Model.
- The International Link: Launched in late 2026, the GLOBE model allows CMS to assess rebates if a US price exceeds an international benchmark of "economically comparable" countries.
- The "Most Favored Nation" (MFN) Pressure: Under the "TrumpRx" platform, the US is moving toward a system where Medicare references the second-lowest price in an OECD basket.
- The Trap: If you don't launch in Europe, CMS can still use "available information" from other comparable markets to set your US benchmark. You lose the revenue from Europe and you still get the price cut in the US.
4. Why Postponing is a Losing Strategy
Postponing a launch to "wait and see" is simply Valuation Decay.
- The Revenue Gap: By not launching, you are walking away from the 20–25% of global revenue that Europe typically represents—money you now desperately need to offset US price cuts.
- The Evidence Gap: If you wait, you lose the opportunity to gather Real-World Evidence (RWE) in Europe that could actually help you defend your value during a CMS negotiation in the US.
๐ฅ THE ULTIMATE TAKEAWAY:
The walls between the US and Europe have fallen. If you are an independent consultant or a VP of Access, you cannot think in silos anymore.
A drug launched 10 years ago in Berlin is now the anchor for a negotiation in Washington D.C. today. At Sur Access, I help you map this "Backtracked Contamination" so you can protect your global floor before the dominos start to fall.
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The "Wait and See" strategy is just a "Wait and Lose" strategy.
THE "CONFIDENTIALITY" CRUTCH IS KILLING YOUR VALUE
23 March 2026
I recently sat across from a VP of Access at a high-flying oncology biotech. I asked a simple question about the reality of Medicare negotiations and the "Global Price Floor."
The response? "We can’t reveal those net prices; our commercial contracts are confidential. CMS won't know the true price after rebates."
I almost dropped my coffee. This isn’t just a "safe" corporate answer—it’s dangerously naive. It’s the kind of "Outdated Playbook" thinking that turns a $1B peak-year-sales forecast into a Valuation Crater.
If your leadership thinks a confidentiality clause is a shield against the most powerful payers on earth, you aren’t just behind the curve. You’re off the map.
1. The "Confidentiality" Myth
Let’s be blunt: Confidentiality clauses protect the Manufacturer, not the Payer. When a VP tells me they "can't" disclose a price to a government entity like CMS or a German sickness fund, they are confusing a marketing preference with a legal mandate.
Payers don’t care about your "List Price" branding—they care about the Net Price. In the era of the Joint Clinical Assessment (JCA) and International Reference Pricing (IRP), the "List Price" is just a ghost in the machine.
2. The IRA: the End of the "Black Box" Strategy
The Inflation Reduction Act (IRA) didn't just change the math; it legally dismantled the "Gag Rule" (the Non-Interference Clause of the 2003 Medicare Modernization Act). For decades, CMS was legally forbidden from negotiating drug prices—they were a "price taker." Those days are over.
· The "Black Box" is Open: The Secretary of HHS now has the mandate to negotiate the Maximum Fair Price (MFP). You can no longer hide behind the "non-interference" shield.
· Mandatory Data Disclosure: Manufacturers are now required to hand over internal "confidential" data—including R&D costs, prior federal support, and unit costs—to justify their pricing.
· The MFP is Public: Once the negotiation is finished, the price is published for the world to see. There is no such thing as a "hidden" net price in the Medicare space anymore.
3. The European Pincer: Transparency vs. Protection
The old world is fracturing, and the "Confidentiality" strategy is failing on both ends:
· Germany: Germany introduced confidential rebates in 2025—but it comes with a massive price tag. If you want to keep your net price out of the public eye to protect your global floor, the German government charges an additional 9% "Confidentiality Tax" on your negotiated price. Only companies with a massive active R&D footprint in Germany qualify. For everyone else, your net price stays public.
· France (The Strategic Fortress): The Conseil d’État still shields net prices—but not to help your margins. They do it to prevent International Reference Pricing (IRP) from causing "market desertion." They protect the secret to keep you in the market, not to protect your global valuation.
· UK: The UK has agreed to pay 25% more for new medicines to "offset" US price reductions. NICE thresholds are rising to £25,000–£35,000, and the VPAG rebate for newer medicines is capped at 15% for 2026 (down from 22.9%).
· Spain (The Crusaders): The tide has turned. The Spanish Supreme Court is currently reviewing whether public interest in drug spending overrides commercial secrets. The "old guard" is losing; transparency is becoming the default.
4. The "Globe and Guard" Reality: CMS Method 1
Here is the wake-up call for those still clinging to their NDAs: Silence is not a strategy; it’s a data gap that CMS will fill for you.
If a manufacturer refuses to disclose their confidential net prices for the "Globe and Guard" price protections, CMS won't just throw their hands up. They will trigger Method 1.
Under Method 1, CMS bypasses the manufacturer entirely and calculates the ceiling using net prices predicted by the industry’s biggest data players—IQVIA and GlobalData.
The Risk: You lose the ability to tell your own story. By withholding data, you hand over your global price floor to third-party algorithms and secondary data sets. CMS will use these estimates to set your ceiling, and if their "predicted net" is lower than your reality? That is your new ceiling.
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THE ULTIMATE TAKEAWAY:
Complexity is the enemy of execution. Stop hiding behind "Confidentiality" and start mastering Resourcefulness.
In the era of IRA, MFN, and JCA, "Approved" does not mean "Paid." If your Access leadership thinks an NDA is a strategy, you are leaving your ROI to chance. You don’t need more "compliance"—you need an Access Architect who understands how the money actually flows.
STOP LEAVING YOUR GLOBAL VALUATION TO CHANCE!
09 March 2026
Most Biotech investors are playing a game they’ve already lost because they are operating on an outdated playbook. They think if they get the EMA or FDA label, they’ve crossed the finish line.
In the new era of the Joint Clinical Assessment (JCA), Approved does not mean Paid. If you aren’t designing for ACCESS from Day One, you aren’t building a breakthrough—you are building a Valuation Crater.
I am Dr. Sanja Fitzgerald. My 17-year journey has taken me from the rigor of a PhD in Computational Chemistry at ETH Zurich to leading global scientific and commercial workstreams. For nearly two decades, I have navigated the translation of complex scientific innovation into market-ready value propositions. Now, I master the Unseen Risks that destroy rNPV in the precision oncology and rare disease markets.๏ปฟ
1. The Safety Trap vs. The Value Victory
Regulators ask: Is it safe?
Payers ask: Is it BETTER?
If your trial beats a comparator but fails against the modern Standard of Care (SoC), you have a Hunting License with no bullets. You must demand Relative Effectiveness or prepare for a massive price discount based on uncertainty.
2. Anticipate the Scoping Explosion
The JCA isn’t one assessment; it’s 27 Member States demanding their own answers. A single oncology drug can trigger 13+ distinct PICOs. If your clinical data isn’t elastic enough to be sliced for every market, you are invisible to the payers who hold the keys to the kingdom.
3. The Global Price Floor is CRACKING
The "Berlin-to-Boston" contagion is real. With International Reference Pricing (IRP) and evolving US policies, a "Low Certainty" report in Europe can legally trigger a price collapse in the US. You aren’t just losing a market; you are losing your Global Price Floor.
4. Execute Shadow PICO Mastery
Why wait 24 months for a rejection when you can map the future today? My Shadow PICO Audit identifies "Non-Recoverable" design flaws—like missing Quality of Life (QoL) data or the lack of an active anchor—while you still have time to pivot. We align your Clinical Development Plan with payer reality to ensure that when you launch, you WIN.
๐ฅ THE ULTIMATE TAKEAWAY:
Stop settling for Regulatory Success and start maximizing Commercial Certainty.
If you want to protect your ROI and ensure your innovation actually reaches the patients who need it, you need an Access Architect.
The Alzheimer’s Valuation Gap: Why MoA Success Needs Digital PROs
10 February 2026
The recent regulatory approvals of Leqembi (lecanemab) and Kisunla (donanemab) mark a historic shift in neurodegenerative care. After decades of "plaque-focused" failures, we have finally moved into the era of disease-modifying therapies (DMTs).
However, as a market access expert, I see a looming crisis: The Valuation Gap. While the Mechanism of Action (MoA) of these drugs—specifically targeting toxic soluble protofibrils—is scientifically robust, our methods for measuring their impact on a patient’s life remain analog, infrequent, and arguably, insensitive.
The Problem: Measuring a Glacier with a Stopwatch
In Alzheimer’s, the traditional "gold standard" for Market Access is the CDR-SB (Clinical Dementia Rating Sum of Boxes). While statistically significant in trials, these drugs often miss the Minimal Clinically Important Difference (MCID)—the threshold where a daughter actually notices her father is better.
Furthermore, Patient-Reported Outcomes (PROs) in Alzheimer’s face a unique "biological wall": Anosognosia. As the disease progresses, patients lose the cognitive insight required to accurately report their own quality of life. We are left relying on "Caregiver-Reported Outcomes" (ObsROs), which are prone to hope-bias and retrospective errors.
The Solution: Passive Digital PROs
If we cannot ask the patient how they feel, we must observe how they function in their natural environment. This is where Digital PROs (dPROs) and Digital Biomarkers become the ultimate tools for Market Access.
Digital PROs move away from "snapshot" clinic visits and toward continuous, objective data:
- Digital Mobility: Using smartphone accelerometry to track gait changes, which often correlate with neurodegeneration before memory loss is evident.
- Linguistic Analytics: AI-driven speech analysis to measure "word-finding pauses" during daily calls—a real-world proxy for cognitive preservation.
- Autonomy Events: Tracking a patient's ability to navigate their neighborhood via GPS or manage a digital wallet.
The EMA’s Stance: A Regulatory Green Light
For those of us navigating European markets, the landscape is shifting. The European Medicines Agency (EMA) has been historically skeptical of "subjective" Alzheimer’s data. However, the EMA is now leading the charge in validating digital health technologies.
In their recent Qualification Opinions, the EMA has signaled a clear path for digital tools in CNS trials:
- The Move to "Slowing the Slope": The EMA recognizes that in DMTs, "buying time" is the primary value. They are increasingly open to digital data that proves a patient has remained in a "mild" state longer than the placebo group.
- Context of Use: The EMA requires that digital PROs be validated for a specific "Context of Use" (CoU). For Alzheimer's, this means the tool must measure a functional outcome that correlates directly with the MoA of the drug.
- The 2025/2026 Pivot: As of late 2025, the EMA has begun emphasizing "Patient-Centric Drug Development," encouraging manufacturers to use wearables to bridge the gap where traditional PROs fail.
The Sur-Access Strategy: De-risking through Evidence
At Sur-Access, we help teams bridge the gap between computational MoA and Market Access success. To win in 2026, you cannot rely on 18-month-old survey data. You need a robust evidence package that includes:
- TCO Analysis: Factoring in the high cost of ARIA monitoring.
- Digital Evidence: Utilizing dPROs to prove that the "statistical win" translates into "societal value" (e.g., delaying nursing home admission).
The key to the Alzheimer’s market isn't just clearing amyloid; it’s proving you’ve cleared a path for the patient to remain "present."
Are you developing a therapy for neurodegenerative disease? Let’s ensure your evidence package is as sophisticated as your molecule.
Autoimmune Disease News: JAK Inhibitor Rinvoq Recommended for Rare Arteritis
1 March 2025
A significant advancement in autoimmune disease treatment is on the horizon. The EMA CHMP has recommended the approval of upadacitinib (Rinvoq) for giant cell arteritis (GCA), a rare and debilitating condition primarily affecting individuals over 50.
GCA, also known as temporal arteritis, involves the inflammation of medium and large arteries, notably the temporal arteries in the head. This inflammation can lead to severe complications, including irreversible vision loss, aortic aneurysms, and debilitating pain, significantly impacting patients' quality of life. While glucocorticoids remain a standard treatment, they carry risks with long-term use.
The CHMP's recommendation brings Rinvoq closer to becoming the first oral advanced therapy for GCA in Europe. The EMA is expected to make a final decision in the first half of 2025.
Rinvoq, a selective JAK1 inhibitor, targets the Janus kinase (JAK) pathway, a key driver of inflammation in GCA. The recommendation is based on compelling results from the Phase III SELECT-GCA trial. This trial, involving 428 patients aged 50 and older, compared Rinvoq to placebo. The trial's primary endpoint, sustained remission at 52 weeks (defined as the absence of GCA signs and symptoms between weeks 12 and 52), was significantly higher in the Rinvoq 15mg group compared to placebo: 46% vs. 29% (P = 0.0019). Similarly, sustained complete remission, a more stringent measure, was achieved in 37% of the Rinvoq group versus 16% of the placebo group (P < 0.0001).
Rinvoq, developed by AbbVie, is already approved in the EU for several other autoimmune conditions. Ongoing trials are exploring its potential in further immune-mediated diseases.
Beyond the Cigarette: Lung Cancer Can Strike Anyone
30 January 2025
๐ซ Lung cancer, the leading cause of cancer deaths worldwide, has seen remarkable treatment progress and improved survival rates in the last decade. NICE's 48 positive treatment recommendations since 2015—a six-fold increase—reflect this progress, bringing innovative therapies like targeted treatments and immunotherapies to patients faster. Jules Fielder's case, diagnosed with stage 4 lung cancer at 37 despite being a non-smoker with no typical symptoms, highlights the disease's indiscriminate nature and the power of targeted therapies like osimertinib. Her experience underscores that lung cancer can affect anyone, regardless of smoking history, and often presents with subtle symptoms.
๐ซ Approximately 95 people die from lung cancer daily in the UK, exceeding breast and ovarian cancer deaths combined. Experts dispel the myth that only smokers get lung cancer (15% of patients are non-smokers) and emphasize that a diagnosis isn't a death sentence. Early diagnosis, when surgery and radiotherapy can be curative, is crucial. Stage 4 prognosis has improved dramatically: from 6-9 months survival a decade ago to 6-7 years now, thanks to targeted therapies and immunotherapies. NICE's increased positive recommendations facilitate faster access to these treatments.
๐ซ Late diagnosis due to absent or overlooked symptoms, as in Fielder's case (back pain misdiagnosed as sciatica, a hoarse voice), remains a challenge. This highlights the need for greater awareness of less common symptoms. While five-year survival rates have improved (from 8.6% in 2005 to 19.8% in 2016), the UK still lags behind other countries. The NHS's lung health checks and the national lung cancer screening program are vital steps toward early detection. The future of lung cancer treatment looks promising, with anticipated advancements in targeted therapies, immunotherapies, and vaccines, though more effective and longer-lasting treatments are still needed.
https://www.nice.org.uk/news/articles/sixfold-increase-in-nice-lung-cancer-treatment-recommendations-over-the-past-decade
EMA Reverses Course on Leqembi, Approves for Restricted Use
5 December 2024
The EMA’s CHMP recent decision to recommend marketing authorization for Leqembi (lecanemab) is a significant development in the treatment of Alzheimer's disease. This comes after a previous negative opinion from the EMA's Committee for Medicinal Products for Human Use (CHMP).
Why the Change of Heart?
The initial negative opinion was based on concerns about the drug's safety profile, particularly the risk of brain swelling and bleeding (ARIA). However, the CHMP's re-examination focused on a specific patient population: those with mild cognitive impairment or mild dementia due to Alzheimer's disease who have one or no copy of the ApoE4 gene. This subgroup was found to have a lower risk of serious side effects.
The ApoE4 gene is a genetic risk factor for Alzheimer's disease. Individuals with two copies of the ApoE4 gene have a significantly higher risk of developing the disease. By focusing on patients with one or no copies of ApoE4, the EMA aimed to mitigate the risk of ARIA.
While this is a positive step forward, it's important to note that Leqembi is not a cure for Alzheimer's disease. It slows cognitive decline but does not reverse it. The reported difference in CDR-SB scores of 0.53 on the scale from 0 to 18 is considered clinically meaningful, being just above the 0.5 threshold. Additionally, the risk of serious side effects, particularly ARIA, remains a concern.
As a result, the drug will be available through a controlled access program to ensure safe and effective use. Patients will undergo regular MRI scans to monitor for ARIA and other potential side effects. The company will set up an EU-wide registry study with patients treated with Leqembi that can be used to estimate the incidence of side effects, including ARIA, and to determine how severe they are. The registry study can also be used to collect information about patients’ progression to the next stages of Alzheimer’s disease and the possible long-term consequences of ARIA.
https://www.ema.europa.eu/en/news/leqembi-recommended-treatment-early-alzheimers-disease#
NICE Rejects Enhertu Again: Cost-Effectiveness Hurdles Persist for Innovative Cancer Therapies
22 November 2024
Daiichi Sankyo and AstraZeneca's antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan), has faced another significant setback, with NICE rejecting the drug for a third time.
This decision has sparked widespread disappointment and frustration, as it deprives thousands of patients with HER2-low breast cancer from accessing a potentially life-extending treatment.
The UK's rigorous cost-effectiveness assessments, while crucial for ensuring value for money, often pose challenges for innovative therapies, especially those treating rare diseases. Enhertu, though demonstrating significant clinical benefit, has apparently failed to meet the stringent cost-effectiveness threshold set by NICE. This decision underscores the complex interplay between clinical efficacy, patient need, and economic considerations in healthcare systems. It highlights the urgent need for innovative financing models and pricing strategies to ensure equitable access to life-saving treatments.
According to GlobalData's Pharma Intelligence Center, Enhertu was projected to achieve $13 billion in global sales by 2030. Had NICE approved the drug, it could have potentially improved outcomes for approximately 1,000 patients with HER2-low breast cancer.
https://www.globaldata.com/newsletter/details/daiichi-sankyo-and-astrazeneca-s-enhertu-snubbed-by-uk-s-nice-for-third-time-_340807
Oncology News: Merck Acquires Modifi Biosciences in a $1.3B Deal to Advance Brain Cancer Treatment by Targeting DNA Repair Deficiencies
31 October 2024
Merck, a global pharmaceutical leader, has acquired Modifi Biosciences, a Yale University spinout, in a strategic deal worth up to $1.3 billion, with an upfront payment of $30M. This acquisition underscores Merck's commitment to advancing innovative therapies and transforming cancer treatment.
The agreement gives Merck access to preclinical compounds designed to exploit DNA repair defects in difficult-to-treat cancers, including glioblastomas, the most aggressive and most common type of cancer that originates in the brain, often resistant to chemotherapy and radiation therapy.
Modifi Biosciences has developed a novel class of small molecule inhibitors targeting O6-methylguanine methyl transferase (MGMT), a key DNA repair protein. By inhibiting MGMT, Modifi's compounds aim to selectively kill cancer cells, particularly those with DNA repair deficiencies, such as glioblastoma.
This acquisition brings together Merck's extensive resources and expertise with Modifi's cutting-edge science. By leveraging this powerful combination, the companies aim to accelerate the development of transformative therapies that address significant unmet needs in oncology.
https://www.pharmtech.com/view/merck-acquires-modifi-biosciences
Ivonescimab (Summit, Akeso) Shows Promise as a Breakthrough Treatment for 1L NSCLC
09 September 2024
In December 2022 a $5 billion deal was signed between Summit Therapeutics (US) and Akeso Inc. (China) to in-license, develop and commercialize ivonescimab, a first-in-class PD-L1/VEGF bispecific antibody for cancer treatment. The upfront payment was $500M. This partnership aims to expand Akeso's reach into key markets like the US, Canada, Europe, and Japan– an important step towards Akeso’s strategic intention of becoming a global biopharma organization.
Recent data from a Phase 3 trial presented last week at the World Conference on Lung Cancer demonstrated the superior efficacy of ivonescimab compared to Keytruda in first-line NSCLC treatment. The drug significantly prolonged median progression-free survival by 5.32 months, reaching 11.14 months. The China-only data are impressive, signaling the PD-1/VEGF bispecific antibody’s potential as a new standard of care in non-small cell lung cancer (NSCLC).
https://www.smmttx.com/wp-content/uploads/2024/09/WCLC-2024-Presentation-HARMONi-2.pdf
mRNA Vaccine for Lung Cancer Trial Launched
30 August 2024
๐ A pioneering mRNA vaccine, developed by BioNTech, is currently being evaluated in clinical trials for the treatment of non-small cell lung cancer (NSCLC), a leading cause of death globally.
๐ This innovative approach, similar to the mRNA technology used in COVID-19 vaccines, leverages the body's immune system to combat cancer. By identifying unique mutations within a patient's tumor, researchers create a personalized mRNA vaccine that instructs the immune system to target and destroy cancer cells.
๐ The potential for this treatment to significantly improve outcomes for lung cancer patients marks a significant step forward in the field of cancer immunotherapy.
https://www.theguardian.com/society/article/2024/aug/23/world-first-lung-cancer-vaccine-trials-launched-across-seven-countries
Aveta Biomics' Investigational Drug Receives Fast Track Designation for Head and Neck Cancer
26 August 2024
๐ง Their investigational immune-oncology agent, APG-157, has been granted fast track designation by the FDA as a neoadjuvant treatment for patients with head and neck cancer.
๐ง APG-157, an orally administered lozenge derived from turmeric, shows promise in reducing tumor size and potentially limiting the need for extensive surgery or radiation. Developers designed APG-157 to exhibit a dual mechanism by selectively inducing cancer cell apoptosis while reprogramming the immune environment. This could significantly improve outcomes for patients with this challenging condition.
๐ง A phase 2 trial is currently underway to further evaluate APG-157's safety and efficacy in treating head and neck cancer.
https://www.cancernetwork.com/view/fda-grants-fast-track-status-to-neoadjuvant-apg-157-in-head-and-neck-cancer
US Government Finalizes Drug Price Negotiations
21 August 2024
A historic milestone has been reached as the US government finalizes prices for the first ten drugs under the Inflation Reduction Act. Negotiated prices for these drugs, including Eliquis (blood thinner), Enbrel (arthritis), Stelara (psoriasis), and Imbruvica (blood cancer), will be significantly lower. Medicare will implement these reduced prices starting in 2026.
Drugmakers and industry groups challenged the law in court but were unsuccessful. While the initial price cuts may seem manageable, concerns are growing for fear the process could lead to bigger financial hits as Medicare targets more medicines.
As per the new drug law, including the Negotiation Program, the government's price-setting process involved extensive data analysis and negotiations with drug companies. Factors considered included research and development costs, manufacturing expenses, data on patents, revenue and market data, and the availability of alternative treatments. CMS considered information from a wide variety of sources.
Despite industry opposition, CMS will select up to 15 additional drugs covered under Part D for negotiation in 2025, and up to an additional 15 Part B and Part D drugs in 2026, and up to 20 drugs every year after that.
Experts predict that high-profile drugs like Ozempic and Keytruda could be targeted in future negotiation rounds, potentially leading to more significant impacts on the pharmaceutical industry.
https://lnkd.in/emJfdu-j
https://lnkd.in/eJi-FAdu
Casgevy: A Case Study in Gene Therapy Launch and Pricing
8 August 2024
Casgevy is one of seven gene and cell-based therapies launched in the US with a price tag exceeding $1M per treatment. It was approved by the FDA in December 2023 for sickle cell disease (SCD) and subsequently for transfusion-dependent beta-thalassemia (TDT).
This groundbreaking CRISPR-based gene therapy for SCD and TDT, offers valuable insights into the commercialization of advanced therapies. With a high launch price of $2.2M per treatment Casgevy aligns with the pricing trend for other gene therapies.
Despite their high upfront costs, gene therapies for sickle cell disease, such as Lyfgenia and Casgevy, exhibit comparable annualized treatment costs to standard-of-care options. For instance, the annual cost of managing SCD with the iron chelator Ferriprox (ca.$3.2M) approximates the cost of these gene therapies, highlighting the potential for long-term cost-effectiveness.
Casgevy followed a typical launch pattern for haematological agents, with the US as the initial market, followed by Luxemburg and Bahrain. In France it is available under the early access scheme since January 2024 and now awaits pricing. The French price could influence pricing in other countries due to France's role in international reference pricing.
Alzheimer's: A Growing Crisis and the Race for a Cure
6 August 2024
Alzheimer's disease is a global health crisis rapidly escalating. Despite recent advancements, effective treatments remain elusive. The blood-brain barrier poses a significant challenge in drug delivery, hindering progress. ๐ง
Recent FDA approvals of lecanemab and donanemab marked a milestone in Alzheimer's treatment, targeting amyloid plaques associated with the disease. However, it seems that EMA is more concerned about the safety of the new drug, citing that the observed effect of Leqembi delaying cognitive decline does not counterbalance the risk of serious side effects (ARIA, amyloid related imaging abnormalities, or brain swelling and bleeding). CHMP (The Committee for Medicinal Products for Human Use) just recommended against the authorization of lecanemab. ๐ง
The search for alternative approaches is intensifying. Companies like Regeneration Biomedical and Excellio are exploring innovative methods, including stem cell therapy and exosome-based drug delivery, to bypass the blood-brain barrier. Passage Bio is focusing on gene therapy to address the root cause of Alzheimer's. Additionally, using focused ultrasound to temporarily open the blood-brain barrier is being investigated.
As research progresses, the hope is to find more effective and safer treatments for Alzheimer's disease. ๐ง
Check our recent post on conditional coverage of Leqembi (lecanemab) in the US.
https://lnkd.in/eXVMnVzC
Breaking News in Cancer Research!
1 August 2024
Telomere-targeting THIO in combination with immunotherapy extends treatment time for advanced NSCLC patients.
I'm excited to share about THIO, a groundbreaking small molecule that's showing promising results in treating non-small cell lung cancer (NSCLC). Developed by MAIA Biotechnology, THIO works by targeting telomeres, leading to rapid cancer cell death.
When combined with cemiplimab (LIBTAYO®), THIO has demonstrated impressive tolerability and efficacy in patients with advanced NSCLC who've exhausted other treatment options. Early data from the phase 2 THIO-101 trial is very promising, with patients showing longer treatment durations and lower toxicity compared to standard treatments.
This is a significant step forward in the fight against cancer!
https://lnkd.in/eBd58tA9
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Biosimilar Undercuts AbbVie Drug Humira by 92%, Shaking Up Market
29 July 2024
Humira, the world's best-selling drug, enjoyed a long period of exclusivity in the US, allowing AbbVie to charge a premium price. But the tides are turning. US patent expiration at the beginning of 2023 opened the door for biosimilars, near-identical copies, and the competition is fierce.
Boehringer Ingelheim employed a price split strategy. In July 2023 they launched a branded biosimilar, Cyltezo, priced just 5% lower than Humira. But Boehringer has struggled to grow sales. To truly disrupt the market, they're now offering an unbranded version through GoodRx at a staggering 92% discount to Humira's list price. This aggressive move could be a game-changer, putting immense pressure on AbbVie and shaking up the biosimilar landscape.
At that price, a typical regimen of one shot every other week for rheumatoid arthritis, Crohn’s disease and other autoimmune disorders would yield an out-of-pocket cost of $7,150 a year. Humira previously cost $7,000 for a four-week supply at the list price.
Humira biosimilars entered the European market in October 2018.
All eyes on TIGIT
21 July 2024
Roche's TIGIT drug candidate, tiragolumab in combination with PD-L1 inhibitor Tecentriq® (atezolizumab), failed to outperform Merck's established PD-1 inhibitor, Keytruda® (pembrolizumab), in a key lung cancer trial (SKYSCRAPER-06).
SKYSCRAPER-06 compared tiragolumab + Tecentriq (atezolizumab, another PD-L1 checkpoint inhibitor from Roche) and chemotherapy to Keytruda and chemotherapy in previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (nSq NSCLC) patients.
Survival data favored Keytruda, with a hazard ratio of 1.33 for overall survival (OS) and 1.27 for progression-free survival (PFS) at the first interim analysis (higher hazard ratio indicates the control, Keytruda, performed better).
This negative outcome prompted Roche to halt SKYSCRAPER-06 and re-evaluate its broader TIGIT program.
https://lnkd.in/etvjth_m
Infertility Market Driven by Demand and Limited Improvement Rates
14 July 2024
The World Health Organization reports that infertility affects roughly 17.5% of the global adult population, driving a growing demand for female infertility treatments. GlobalData predicts this market to reach $2.3 billion by 2033 in major markets like the US, Europe, and Japan.
Current infertility drugs primarily address ovulation issues and hormonal imbalances. They work by stimulating egg production or regulating menstrual cycles to create a more favorable environment for conception. Examples include Clomid, Femara, and injectable Gonadotropins.
Despite advancements in stimulating egg production, embryo manipulation, and culture techniques used in In Vitro Fertilization (IVF), there haven't been significant improvements in live birth rates.
Spanish biotech company Oxolife presents a promising development with their non-hormonal fertility pill, OXO-001. Early Phase II data shows positive results in increasing the chances of embryo implantation in women undergoing IVF.
OXO-001 targets the uterine lining (endometrium) to enhance its receptivity for embryo implantation. Phase II results showed a significant increase in early pregnancy confirmation rates (75.9% vs. 52.4%) and clinically confirmed pregnancies with fetal heartbeat (50% vs. 35.7%) in the OXO-001 group compared to the placebo group.
While live birth rates in the OXO-001 group remained promising (42.6%) compared to placebo (35.7%) at 10 weeks post-embryo transfer, Oxolife cautions that the Phase II trial wasn't designed to definitively prove statistical significance. A larger Phase III trial is planned to confirm these encouraging results.
Shifting Landscape: Coverage for New Alzheimer's Drugs
03 July 2024
In 2022, the Centers for Medicare and Medicaid Services (CMS) took a cautious stance on the controversial Alzheimer's drug Aduhelm (aducanumab). Medicare wouldn't cover the drug until positive results were shown in government-approved trials. This decision reflected Aduhelm's accelerated FDA approval in 2021, which required confirmation of clinical benefit in further studies. As the first new Alzheimer's drug in nearly two decades, Aduhelm generated excitement. However, pivotal trials revealed limited clinical benefit for patients, despite reducing amyloid beta plaque in the brain. While high levels of this protein are linked to Alzheimer's, the evidence connecting its reduction to improved brain function or slowed disease progression remained weak.
Faced with physician resistance and low demand, Biogen, the manufacturer of Aduhelm, slashed the initial price from a staggering $56,000 to $28,000 per year per patient. Ultimately, in 2024, Aduhelm was withdrawn from the market, and the confirmatory study needed for full approval was halted.
A different story unfolded for newer Alzheimer's drugs. Eisai and Biogen's Leqembi (lecanemab) received accelerated approval for early Alzheimer's disease in January 2023, followed by full approval in June of the same year. This full approval was based on evidence demonstrating a higher likelihood of slowing cognitive decline. The European Medicines Agency (EMA) is still evaluating Leqembi.
Similarly, Lilly's Kisunla (donanemab) secured FDA approval for early symptomatic Alzheimer's disease in the summer of 2024.
With these newer drugs demonstrating clinical benefit, CMS has adjusted its reimbursement position. However, coverage is now conditional on collecting patient data in registries. This data will provide real-world evidence on how these drugs function once they receive full FDA approval.
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Big Pharma Embraces AI: Partnering for Faster Drug Discovery
01 July 2024
Traditionally, Big Pharma companies haven't had robust in-house AI capabilities. However, this is changing rapidly. Recognizing the potential of AI to revolutionize drug development, they are increasingly open to collaborating with external vendors offering cutting-edge tools. These tools can streamline and accelerate the drug pipeline, leading to faster breakthroughs for patients.
Bristol-Myers Squibb (BMS) partnered recently with deep tech company VantAI for a staggering $674 million to leverage AI in designing "molecular glues" - a promising new class of small-molecule therapeutics. Sanofi entered a collaboration with Aqemia, a leader in applying genAI and deep physics algorithms to drug discovery, in a $140 million deal. Genentech joined forces with tech giants Amazon and NVIDIA to create a next-generation AI platform specifically for their drug discovery and development efforts, bridging the gap between science and technology.
Early results are encouraging. Data suggests that AI-discovered molecules are performing well in clinical trials, with some analyses reporting success rates as high as 80-90% in Phase I. While this success rate naturally tapers off in later stages (around 40% in Phase II), it still represents a significant improvement over traditional methods.
Looking ahead, the widespread adoption of generative AI (genAI) has the potential to disrupt the entire drug industry. We can expect faster drug discovery processes, more efficient and informative clinical trials, and ultimately, more affordable drugs that reach a wider range of patients.
AI in Pharmaceutical Negotiations: A Promising Future with Regulatory Considerations
25 June 2024
A recent podcast discussion regarding the use of AI and biometric emotional response measurement during payer negotiations for drug pricing sparked my interest, particularly as a computational chemist with over 15 years of experience in digital drug discovery methods. While this specific application presents ethical and regulatory challenges, the potential of AI in the pharmaceutical industry is undeniable.
Digital and AI-powered systems have revolutionized drug discovery. They can predict drug-protein interactions, design new drugs from scratch (de novo design), and screen potential drugs for activity, toxicity, and other properties. This significantly reduces preclinical research costs and accelerates the discovery of valuable new therapies. AI also holds immense promise for streamlining clinical trials, potentially reducing costs and increasing success rates.
The collection of electronic patient outcome data allows for real-time tracking and evaluation. However, regulations are crucial for responsible AI implementation. The European Parliament's adoption of the European AI Act (AIA) in March 2024, anticipated to be in effect by June 2024, is a step in the right direction.
The European Commission recognizes the potential of AI in healthcare but acknowledges potential risks. The AIA establishes a risk-based approach, classifying AI systems with corresponding requirements and obligations. Providers and users of high-risk systems will need to comply with stricter regulations.
The new regulations ban specific AI applications that threaten citizens' rights. This includes biometric categorization based on sensitive data, unauthorized facial recognition databases, and emotion recognition in certain contexts. Additionally, social scoring, predictive policing solely based on profiling, and manipulative AI are prohibited.
While the use of biometric methods and AI in payer negotiations raises ethical concerns, AI has the potential to be a powerful force for good in the healthcare system. By prioritizing ethical considerations and focusing on applications that benefit patients and the entire system, we can harness the power of AI for positive change.
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EMA Tightens Transparency Rules for Clinical Trials
21 June 2024
The EMA has launched a new version of the Clinical Trials Information System (CTIS) public portal, which will allow for quicker and more efficient access to information about clinical trials being conducted in the EU for patients, healthcare professionals and other stakeholders. To be seen if the updated rules will strike a balance between transparency of information and the protection of commercially confidential information.
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