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ALETH / LIFESCI-BRIEF / 2026-02-27 / CAGRISEMA LOSES VS ZEPBOUND HEAD-TO-HEAD

CagriSema loses vs Zepbound head-to-head

Also this week: Gilead agrees to buy Arcellx for $7.8bn, the FDA proposes a pathway for bespoke genetic medicines & Roche unvelied its $150 human genome Axelios sequencer at AGBT.

The Aleth Briefs trace each story to its original source and show how the week unfolded.

The week in five lines:

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Weekend catch-up

The US Supreme Court struck down Trump’s global tariffs, while pharma escaped the replacement.

The court ruled 6-3 that the International Emergency Economic Powers Act does not give the president authority to impose tariffs. The White House responded the same day with a temporary 10% import surcharge under section 122 of the Trade Act, but pharmaceuticals and APIs were exempted. Drugmakers had spent the prior year restructuring supply chains around the now-invalidated regime. The immediate threat has receded, but the authority to target pharma through other statutes survives.

Monday 23 February

Novo Nordisk’s CagriSema failed its head-to-head with Zepbound.

In the open-label REDEFINE 4 trial Novo’s CagriSema - a combination of cagrilintide, an amylin analogue, and semaglutide - failed to show non-inferiority on weight loss versus Lilly’s single-molecule dual GIP/GLP-1 agonist Zepbound (tirzepatide) 15 mg at 84 weeks. CagriSema delivered 20.2% weight loss against 23.6% for tirzepatide.

CagriSema was Novo’s best shot at closing the efficacy gap with Zepbound, and the head-to-head result leaves Lilly clearly ahead for now. A higher-dose CagriSema study starts in H2 2026, with REDEFINE 11 reporting H1 2027. An FDA decision on the filed dose is expected by late 2026. Novo shares fell >12% in early Copenhagen trading.

Gilead agreed to buy Arcellx for $7.8bn.

Gilead will pay $115/share in cash plus a $5 contingent value right, converting its 2022 anito-cel collaboration into full ownership and eliminating its existing profit share, milestones and royalties. Arcellx’s BCMA CAR-T is already under FDA review in fourth-line multiple myeloma, with a decision due by 23 December 2026. The deal gives Gilead full control of one of the leading challengers to J&J’s Carvykti and adds another major asset to a cell therapy franchise led by Yescarta and Tecartus.

The FDA proposed a pathway for bespoke genetic medicines.

The Plausible Mechanism Framework for individualised therapies targets genetic diseases with a known biological cause. Rather than follow conventional development, the FDA would allow evidence on bespoke treatments from related products, mechanistic understanding and prior manufacturing experience to support approval.

The framework formalises the kind of case-by-case approach used for therapies such as the custom CRISPR treatment given to baby KJ. If it works as intended, it could materially shorten development timelines for ultra-rare genetic diseases.

Gossamer Bio’s seralutinib failed its phase 3 in pulmonary arterial hypertension.

The inhaled PDGFR inhibitor improved six-minute walk distance by a placebo-adjusted 13.3 metres at week 24, but missed the trial’s prespecified statistical threshold despite a nominal p=0.0320. Seralutinib had been positioned as the nearest challenger to Merck & Co’s Winrevair. Gossamer shares fell 77%. Enrolment in the follow-on SERANATA study was paused, and the company plans to discuss a path forward with the FDA. Chiesi co-develops the drug.

Merck is splitting its human health business ahead of the Keytruda patent cliff.

Oncology will become a standalone division under Jannie Oosthuizen, while a separate specialty, pharma and infectious diseases unit will be led by Brian Foard, joining from Sanofi. Keytruda generated $31.7bn of Merck’s $58.1bn pharma sales in 2025 and loses US exclusivity in 2028. The new structure gives oncology its own leadership while focusing on the portfolio that must replace Keytruda’s earnings.

Astellas took co-rights to Vir’s masked T-cell engager for prostate cancer in a deal worth up to $1.7bn.

Vir gets $335m upfront and near-term milestones for VIR-5500, a dual-masked PSMA T-cell engager in phase 1 prostate cancer. The companies split US profit and loss equally, with Vir eligible for another $1.37bn plus ex-US royalties. The deal funds Vir’s oncology push and gives Astellas another prostate cancer asset alongside Xtandi.

BioMarin is pulling its haemophilia A gene therapy Roctavian from the market.

The withdrawal follows October’s decision to seek a buyer. None emerged, and BioMarin says the move is unrelated to efficacy or safety. Approved in Europe in 2022 and the US in 2023 at a $2.9m list price, Roctavian never achieved expected uptake, highlighting that one-time gene therapies with imperfect durability are commercially difficult at multi-million-dollar prices, particularly where existing treatment is strong.

Ultima Genomics launched its UG200 sequencing series at AGBT.

The UG200 and UG200 Ultra run the company’s Solaris 2.0 workflows, with the Ultra targeting more than 60,000 30x genomes a year. US pricing starts at $850,000, with shipments due from Q2. Ultima is pushing further into the high-throughput sequencing market where Illumina has historically been strongest.

Tuesday 24 February

Novo Nordisk will reset US semaglutide list prices to $675.

From January 2027, Wegovy, Ozempic and Rybelsus will all list at $675 a month, cutting Wegovy’s sticker price by half. Net prices are already substantially lower after rebates, so the immediate revenue effect may be limited, but the move further dismantles the old $1,000-plus per month US GLP-1 pricing model.

Pfizer’s Braftovi combination won full approval in first-line colorectal cancer.

The FDA converted Braftovi (encorafenib) with Erbitux (cetuximab) and chemotherapy to full approval in BRAF V600E-mutant metastatic colorectal cancer. BREAKWATER showed a 51% reduction in the risk of death, removing the confirmatory-data overhang for the only targeted first-line regimen in this population.

15 US states sued the federal government over the childhood vaccines schedule.

The lawsuit challenges the January decision that removed seven vaccines from universal recommendation, including hepatitis A and B, influenza, Covid-19 and RSV, as well as the replacement of ACIP’s membership. The states are asking the court to overturn both, moving the dispute over US vaccine policy into the courts.

Wednesday 25 February

GSK agreed to buy 35Pharma for $950m in cash.

The Canadian biotech’s lead asset HS235 is a clinical-stage activin signalling inhibitor for pulmonary arterial hypertension (PAH) and PH with preserved ejection fraction heart failure. The pathway is validated by Merck’s Winrevair, which sold $1.4bn last year. HS235 data suggest fat-selective weight loss and improved insulin sensitivity. GSK’s move comes two days after Gossamer’s failure thinned the PAH pipeline.

Gilead and Merck both reported late-stage data for new daily HIV pills.

Gilead’s bictegravir/lenacapavir single tablet maintained virological suppression in switch patients in ARTISTRY-1, while Merck reported phase 3 data for its two-drug doravirine/islatravir regimen. Both companies plan regulatory filings, as they try to simplify daily oral therapy even as longer-acting regimens move toward weekly dosing.

Thursday 26 February

Lilly’s orforglipron beat Rybelsus in a head-to-head diabetes trial.

In ACHIEVE-3, orforglipron 36 mg reduced A1C by 2.2% versus 1.4% for Rybelsus 14 mg on the efficacy estimand, with 9.2% weight loss versus 5.3%. On the treatment-regimen estimand, the gap narrowed to 1.9% versus 1.5%. Adverse-event discontinuations were roughly twice as high with orforglipron.

Three days after Zepbound beat CagriSema head-to-head, this compounds a difficult week of direct comparisons for Novo. Orforglipron is filed in >40 countries. As a small molecule it offers Lilly easier manufacturing and supply than peptide GLP-1s.

argenx’s Vyvgart succeeded in ocular myasthenia gravis.

The phase 3 ADAPT OCULUS trial met its primary endpoint, with no new safety signals, supporting a US filing to expand Vyvgart into the ocular form of the disease. It is the first registrational study of a targeted treatment in ocular myasthenia gravis.

BMS and SystImmune’s bispecific ADC hit survival endpoints in breast cancer.

Izalontamab brengitecan, the EGFRxHER3 ADC BMS licensed for $800m upfront in 2023, improved both progression-free and overall survival at an interim analysis of a Chinese phase 3 trial in triple-negative breast cancer. It is the drug’s third positive phase 3 result and the first dual PFS/OS win for a bispecific ADC in the disease.

Asahi Kasei agreed to buy Germany’s Aicuris for €780m.

The Japanese group is acquiring the antiviral specialist through US subsidiary Veloxis, gaining the Prevymis royalty stream and pritelivir, which met its phase 3 primary endpoint in refractory herpes simplex infection in immunocompromised patients. The deal adds a focused infectious-disease portfolio built around transplant medicine.

Hernexeos won rapid first-line approval in lung cancer, only 44 days after filing.

The FDA granted accelerated approval to Boehringer Ingelheim’s Hernexeos for first line HER2-mutant non-small cell lung cancer, based on a 76% response rate in treatment-naive patients. It is the second approval through the National Priority Voucher route, giving an early indication of how quickly the pathway can move.

Caris reported interim data on its multi-cancer blood test.

In 2,122 samples from Achieve 1, Caris Detect showed 56.8% sensitivity at stage I, rising to 99.1% at stage IV. Specificity was 99.1% in 121 asymptomatic participants and 95.3% in the 1,505-person undiagnosed population. A blinded validation in about 865 held-out samples is due later in Q1.

Roche unveiled its Axelios sequencer, targeting a $150 human genome.

Roche revealed details of its sequencing-by-expansion chemistry in early 2025. At AGBT it unveiled the instrument, Axelios 1, which is due to launch later this year, targeting a $150 whole human genome at scale. Roche will enter the sequencing market with an instrument, an aggressive cost claim and the balance sheet to compete, adding further pressure on Illumina and its emerging challengers.

Advances in Genome Biology and Technology (AGBT) · Roche

Generate Biomedicines priced its IPO at $400m.

The Flagship-founded protein design company sold 25m shares on Nasdaq at $16. Trading under GENB begins Friday. Its lead asset, GB-0895, is an AI-engineered anti-TSLP antibody already in phase 3 severe asthma trials, with twice-yearly dosing under evaluation. The IPO is therefore a relatively advanced public-market test of generative protein design rather than another preclinical AI platform story.

Friday 27 February

Illumina launched TruPath Genome and detailed its NovaSeq X roadmap at AGBT.

TruPath Genome is designed to compete with long-read sequencing, which Illumina says doubles the throughput of competing long-read methods. The company also outlined an 18-month NovaSeq X roadmap increasing output 40% to 35bn reads per flow cell, alongside Q70 duplex accuracy for specialised high-sensitivity applications.

MGI conceded its sequencer infringes Oxford Nanopore’s Australian patents.

MGI accepted in the Federal Court (Australia) that its Cyclone SEQ WT02 infringes four Oxford Nanopore patents, leaving infringement itself undisputed ahead of a 2027 trial on remaining defences and damages. Separate UK High Court proceedings against MGI/BGI entities continue over trade-secret infringement and breach of confidence.

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