Novo's CagriSema Loses to Zepbound, Grail Stumbles, FDA Hardens Its Stance – This Week in Biotech #91
CagriSema lost the obesity head-to-head with Lilly's Zepbound, Galleri misses its primary endpoint, and the FDA signals tougher tolerance for invasive rare disease delivery (Feb 20-26, 2026).
Welcome back to This Week in Biotech by Biotech Blueprint, edition 91, covering biotech and biopharma news from February 20th to 26th, 2026.
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VIDEO SUMMARY
THIS WEEK’S KEY TAKEAWAYS 🔑
Yesterday the FDA commissioner went on CNBC and drew a pretty blunt line. Without mentioning a company by name, he said that if a rare disease therapy requires drilling a burr hole into someone’s skull, don’t expect the agency to shrug off the procedure risk just because the need is high. The market took it personally and uniQure’s stock dropped about 30%. And while he may have been talking about a different program, investors heard the broader point loud and clear - the FDA’s patience for invasive, high-morbidity delivery is thinning, and nobody wants to be the next test case.
Vaccine policy is getting more unstable in ways that actually affect schedules, coverage, and manufacturer planning. The CDC pulled its February vaccine advisory committee meeting after the lawsuit pressure (by AAP and other medical groups), rescheduled it for March 18-19, and the agenda now includes COVID-19 vaccine injuries and long COVID. Mainstream medical groups are treating this like an emergency, not a normal policy disagreement, because they think the process is being reshaped in a way that will push recommendations toward lower vaccination rates.
Gene therapy had a reality check this week. BioMarin pulling Roctavian after failing to find a buyer is the clearest sign yet that one and done cures are still commercially fragile. It is not just the science, it is reimbursement, eligibility, logistics, and a standard of care that keeps getting better. And the uncomfortable takeaway is that approval is no longer the finish line, it is just the beginning for a very hard commercialization marathon.
Gilead buying Arcellx feels like a simple call. Anito-cel looks legit, and Gilead doesn’t want to share the upside anymore. But they’re still hedging with that earnout, basically agreeing to pay extra if the drug really sells. And Novo Nordisk finally did the obesity head-to-head everyone’s been debating (CagriSema vs Lilly’s Zepbound) and it lost. Not by a ton, but in obesity, close still counts as losing, at least for now in investors’ eyes. If Novo wants to change the conversation, it has to win on something people actually feel, like fewer dropouts, better tolerability, better outcomes, or a higher-dose version that clearly beats tirzepatide.
And lastly there’s Grail. A large National Health Service trial in the UK missed its primary endpoint, which is a real hit to the idea that this test is ready for population-wide screening. Yes, they can highlight secondary signals and argue the picture could improve with more digging, but the market reaction is understandable. These tests only matter if they reliably move diagnoses earlier at scale, in messy real-world care with real follow-up, not just in theory. That’s the standard now.
BIOTECH/PHARMA NEWS 🧬
🔹 uniQure sold off after FDA Commissioner Marty Makary said on CNBC the agency will not approve rare-disease therapies that require invasive delivery with meaningful procedure-related morbidity, citing a “burr hole” brain-delivery example and a trial showing no benefit. Investors took it as a warning shot at AMT-130, though at least one analyst argued the remarks may fit an already-rejected intraventricular program more closely than uniQure’s.
🔹 CRISPR Therapeutics shares popped on fresh takeover chatter, with traders circulating a Betaville “uncooked” alert suggesting Vertex may be exploring an acquisition. Nothing is confirmed, but the logic is obvious: Vertex already co-developed Casgevy with CRISPR, so buying CRISPR would consolidate control over the partnership and pipeline while the market is quick to reprice on any whiff of M&A.
🔹 ACIP meeting update: After major medical groups sued to stop the CDC’s vaccine advisory committee meeting, the CDC pulled the late-February dates and has now rescheduled ACIP for March 18-19, 2026. The Federal Register agenda adds discussions and possible votes on COVID-19 vaccine injuries and long COVID, alongside ACIP recommendation methodology, with written public comments open March 2-12. The lawsuit is still the backdrop here, and the practical effect is the same: when the advisory process is being challenged and reshaped in real time, vaccine guidance, coverage expectations, and manufacturer planning all get harder.
🔹 BioMarin is pulling Roctavian, its hemophilia A gene therapy, after a multi-month search for a buyer went nowhere. The company will take roughly a $240M hit tied mainly to inventory write offs and asset impairments, underscoring how hard it has been to make one time gene therapies work commercially at scale. Roctavian was approved in 2023 and still grew to $36M in 2025 sales, but uptake stayed limited amid reimbursement friction, eligibility constraints, and strong competition from established hemophilia options.
🔹 Most Favored Nation pricing is back in the spotlight, and a new trade group is forming around the fear that it hits smaller innovators differently than big pharma. Fierce Biotech reports that 10 mid-sized biotechs have launched the Midsized Biotech Alliance of America to oppose MFN, arguing that a diversified pharma can absorb price caps across a portfolio, while a one asset biotech cannot. If MFN becomes a blunt tool rather than a targeted policy, the predictable second-order effect is fewer big, expensive phase 3 bets and more early partnering or asset sales, which means less upside but also less innovation risk taken in-house. Lower prices are the point; the open question is whether MFN can deliver them without quietly shrinking the pipeline that produces tomorrow’s drugs.
🔹 Sarepta Therapeutics said CEO Doug Ingram will step down by the end of 2026, with the board launching a search for a successor and Ingram staying on until a new chief is named. He said the decision was driven by family circumstances: his wife and son were recently diagnosed with myotonic dystrophy type 1, a disease Sarepta began working on in 2024 via a partnership. Ingram’s tenure featured rapid growth on the back of multiple Duchenne muscular dystrophy approvals, including the Elevidys gene therapy, but also major controversy and scrutiny tied to gene therapy safety.
🔹 Vir Biotechnology jumped after signing a global development and commercialization deal with Astellas to advance VIR-5500 in metastatic prostate cancer. The economics are meaningful for a company of Vir’s size: $335M in upfront and near term payments, up to $1.37B in milestones, and tiered double digit royalties outside the U.S., with Astellas covering 60% of development costs.
🔹 MacroGenics’ lead program lorigerlimab is now under an FDA partial clinical hold: no new patients can be enrolled in its Phase 2 LINNET trial after one patient died following Grade 4 neutropenia and septic shock, and three other patients had severe events (including Grade 4 thrombocytopenia and Grade 4 myocarditis). 41 patients have been dosed so far, and current participants can stay on treatment while the company works with the agency on protocol changes and enhanced monitoring to try to lift the hold.
🔹 Gilead agreed to buy Arcellx for $7.8B and giving Gilead full control of anitocabtagene autoleucel (anito-cel), their BCMA-directed CAR-T therapy for multiple myeloma. The contingent payment only triggers if anito-cel reaches $6B in cumulative global net sales from launch through the end of 2029, so Gilead is paying for upside but trying to keep discipline. The near term key question is regulatory: the FDA has accepted the BLA for anito-cel in fourth line relapsed or refractory multiple myeloma with a Dec. 23, 2026 action date, and Gilead says the deal becomes earnings per share accretive in 2028 and beyond if approved.
🔹 Vanda said the FDA approved Bysanti (milsaperidone) for bipolar I disorder and schizophrenia, sending the stock up about 44% after hours. Milsaperidone is the active metabolite of iloperidone, which Vanda previously sold as Fanapt, and Vanda says studies found the two drugs are bioequivalent. The company is also studying Bysanti in phase 3 as an add on treatment for major depressive disorder.
CLINICAL TRIAL UPDATES 📊
🔹 Protara’s phase 2 ADVANCED-2 update for TARA-002 in high risk non-muscle invasive bladder cancer looked mixed on durability, which is why the stock sold off despite solid early complete response rates. In the Bacillus Calmette-Guérin (BCG) unresponsive cohort, complete response was 68% at six months but only 33% at 12 months. In the BCG naïve cohort, complete response was 67% at six months and 58% at 12 months, roughly in line with the prior data cut. Safety stayed clean with no grade 3 or higher treatment-related adverse events, and the company is still guiding to start its registrational BCG naïve trial in the second half of 2026 while finishing enrollment in the unresponsive registrational cohort later in 2026.
🔹 Novo Nordisk’s obesity head-to-head trial landed cleanly and not in Novo’s favor. In the open label phase 3 REDEFINE 4 trial (84 weeks, 809 adults with obesity plus comorbidities), CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg) missed the primary endpoint of non-inferiority versus Eli Lilly’s tirzepatide (Zepbound) 15 mg on weight loss. On-treatment weight loss was 23.0% for CagriSema versus 25.5% for tirzepatide, and with discontinuations included it was 20.2% versus 23.6%. Novo highlighted a safe, well-tolerated profile with mostly mild to moderate gastrointestinal effects that eased over time and argued the amylin add on still delivers clinically meaningful lift beyond GLP-1 alone, but the commercial reality is that obesity markets reward the winner, not close. With CagriSema already filed in the U.S. with a decision expected in late 2026, Novo now needs differentiation that changes behavior, such as better persistence and tolerability, stronger outcomes beyond weight, or a higher dose path.
🔹 Grail’s NHS-Galleri trial in the UK missed its primary endpoint. Adding annual Galleri screening did not significantly reduce combined stage 3 to 4 cancers in a 142k person randomized study. Grail highlighted secondary signals including fewer stage 4 diagnoses in a pre-specified 12 cancers with highest mortality group and plans deeper analyses ahead of ASCO 2026, but the miss is a hit to the “population screening” story.
Have a great rest of your week and thanks for reading Biotech Blueprint!
