FDA Approves the First PROTAC in History, a $1B siRNA Wave Hits Cardiometabolic Disease, and Cytokinetics Cracks Non-Obstructive HCM – This Week in Biotech #99
Targeted protein degradation gets its first regulatory template, Madrigal and GSK bet on genetically defined MASH and obesity, and aficamten wins where Camzyos failed (May 1-7, 2026).
Welcome back to This Week in Biotech by Biotech Blueprint, edition 99, covering biotech and biopharma news from May 1st to May 7th, 2026.
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VIDEO SUMMARY
THIS WEEK’S KEY TAKEAWAYS 🔑
The biggest story this week is a modality. The FDA approved Veppanu on May 1, the first PROTAC protein degrader ever cleared by the agency, in ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer. The Phase 3 numbers are modest: median progression-free survival of 5 months versus 2.1 months on fulvestrant in the ESR1-mutated subgroup, and the broader trial population missed statistical significance entirely, which is why the label is restricted to patients with a confirmed ESR1 mutation identified by a companion diagnostic blood test. None of that matters as much as the fact that targeted protein degradation now has a regulatory template. PROTACs work by recruiting cellular machinery to destroy a disease-causing protein entirely rather than just blocking it, and the field has been waiting years for proof that the FDA would accept this pharmacology at the registration level.
The second theme running through the week is precision medicine moving into common diseases. Two siRNA deals landed within 48 hours. Madrigal paid Arrowhead $25M upfront and up to $975M in milestones for an siRNA targeting a single genetic variant, the PNPLA3 I148M mutation, that drives MASH progression in about 30% of patients with moderate to advanced fibrosis. The Phase 1 data showed 46% liver fat reduction in patients carrying two copies of the variant and zero effect in those carrying one, which is about as clean a genetic signal as you will see in a complex metabolic disease. GSK followed the next day with a $1B deal for SiranBio’s ALK7-targeting siRNA, designed to reduce visceral fat while preserving lean mass, a profile that could complement GLP-1s rather than compete with them. Both are siRNA, both treat conditions historically owned by small molecules, and both are explicit bets that genetically defined patient subgroups are worth pursuing even when the overall population is large.
Obesity is now an earnings story. Novo Nordisk reported oral Wegovy pulling in roughly $355M in its first full quarter on the market, about double consensus, on 1.3M prescriptions. Total Q1 sales were up 32% on a constant currency basis. None of the bear cases on GLP-1 pricing pressure are showing up in actual results.
Cytokinetics had an important week. Aficamten hit both primary endpoints in non-obstructive hypertrophic cardiomyopathy, a form of the disease where there is currently no approved disease-modifying therapy and where BMS’s Camzyos has repeatedly failed. The placebo-adjusted efficacy improvements are modest on paper, but the trial swept the secondary endpoints too, and the indication is wide open. A safety flag around cardiac function will mean echo monitoring in any approved label, but that's routine in cardiology.
BIOTECH/PHARMA NEWS 🧬
🔹 The FDA approved Arvinas’ Veppanu (vepdegestrant) on May 1, eight months ahead of its scheduled review date, for adults with ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer after at least one prior line of endocrine therapy. In the Phase 3 VERITAC-2 trial, median progression-free survival was 5 months on vepdegestrant versus 2.1 months on fulvestrant in the ESR1-mutated subgroup, a 43% reduction in progression or death risk. The broader trial population missed statistical significance, confining the label to ESR1-mutated patients identified by the Guardant360 companion diagnostic blood test. Arvinas and Pfizer are not launching directly and are seeking a third-party commercialization partner, an unusual setup that likely reflects the narrow, biomarker-gated patient population. This is the first PROTAC heterobifunctional protein degrader ever approved anywhere, and it gives every other degrader program in development a regulatory roadmap.
🔹 Cytokinetics reported that aficamten hit both primary endpoints in the Phase 3 ACACIA-HCM trial in non-obstructive hypertrophic cardiomyopathy. Quality of life score improved 11.4 points versus 8.4 on placebo, and peak oxygen uptake improved 0.64 mL/kg/min versus a 0.03 decline on placebo. Secondary endpoints including functional class improvement and a key cardiac stress marker all hit with p less than 0.001. The safety flag: 10% of aficamten patients dropped their left ventricular ejection fraction below 50% versus 1% on placebo, with two serious heart failure events linked to that drop. Echo monitoring will be in any label. Cytokinetics has not given a regulatory submission date but says it will discuss findings with the FDA shortly.
🔹 Entrada Therapeutics reported early Phase 1/2 data for ENTR-601-44 in Duchenne muscular dystrophy patients with exon-44 amenable mutations. The 6 mg/kg cohort showed a mean dystrophin increase of 2.36% from a 4.00% baseline and a statistically significant improvement on a timed Rise from floor test, with no serious adverse events. Drug exposure in younger patients came in below adult levels, so the next cohort is now dosing at 12 mg/kg with more data expected by year end. The numbers are small and early, but a functional signal on top of a biomarker signal in a disease with very few options is enough to keep watching.
🔹 Madrigal licensed ARO-PNPLA3 from Arrowhead for $25M upfront and up to $975M in milestones, adding a precision siRNA alongside Rezdiffra, the only approved MASH drug. ARO-PNPLA3 targets the PNPLA3 I148M variant that drives liver fat accumulation in MASH, showing 46% liver fat reduction in patients carrying two copies of the variant and essentially no effect in those carrying one. Roughly 30% of MASH patients with moderate to advanced fibrosis carry two copies. The asset was originally co-developed with J&J before being deprioritized in 2023. Madrigal plans a Phase 2 combination trial with Rezdiffra, which starts to build a precision medicine MASH platform rather than a single asset story.
🔹 GSK agreed to pay up to $1B in milestones to license SA030, an siRNA targeting ALK7, from China-based SiranBio. ALK7 inhibition is designed to reduce visceral abdominal fat while preserving lean muscle mass, addressing one of the meaningful criticisms of GLP-1s, significant lean mass loss alongside fat loss. SiranBio retains China rights and runs the Phase 1 and GSK takes everything else. Two China-sourced siRNA assets in big pharma’s hands in 48 hours signals the modality is now platform and mature enough that large companies are licensing in rather than building from scratch.
🔹 Novo Nordisk reported first quarter sales of roughly $15.2B, up 32% on a constant currency basis, with oral Wegovy pulling in approximately $355M in its first full quarter, about double analyst consensus on roughly 1.3M prescriptions. Full year guidance was narrowed upward. Novo’s first mover advantage in the oral GLP-1 format is showing up in the numbers despite Lilly’s Foundayo entering the market in April.
🔹 Pfizer reported Q1 revenue of $14.45B, up 5% year over year, with Eliquis growing 13% to $2.17B and Comirnaty falling 59% to $232M. Full year guidance was reaffirmed. With the Metsera acquisition closed at roughly $7 billion enterprise value, Pfizer now owns MET-097i, a weekly and monthly injectable GLP-1 heading into Phase 3, plus a monthly amylin and an oral GLP-1 in Phase 1. The Lilly/Novo duopoly formally has a third serious contender.
🔹 Seaport Therapeutics and Hemab Therapeutics both priced upsized IPOs at $18, the top of their ranges, raising a combined $556M. April was the strongest biotech IPO month in five years. Institutional appetite for late stage biotech is back, but only for programs with clean data and a credible near term catalyst.
🔹 Q1 earnings data points. Vertex reported $2.99B in Q1 revenue with Casgevy at $43M and new pain drug Journavx at $29M on over 350k prescriptions in its first quarter. Bristol Myers Squibb reported Camzyos approaching 25k US patients. Regeneron reported Dupixent global sales of $4.9B, up 33%, while the overall Eylea franchise declined 10% as the newer HD formulation cannibalizes the original.
WATCHLIST 👀
Revolution Medicines: ASCO plenary LBA5 (daraxonrasib in 2L PDAC) on May 31, the dominant near-term oncology catalyst. Merck-Revolution acquisition talks reportedly broke down on price in late January at the $28B-$32B level
IDEAYA Biosciences: ASCO LBA on darovasertib + crizotinib in HLA-A*02:01-negative uveal melanoma; NDA filing H2 2026
Aficamten: Cytokinetics regulatory path discussion with FDA following ACACIA-HCM positive readout. Market expects label-expansion path with echo monitoring
Veppanu launch: Arvinas-Pfizer third party commercialization partner selection; Q1 prescription metrics will set the bar for PROTAC class commercialization
MET-097i (Pfizer-Metsera): VESPER-5 Phase 3 obesity readouts beginning across 10 pivotal studies in 2026
Foundayo (Lilly orforglipron): Q2 prescription run rate, the Q2 test of oral GLP-1 demand against Wegovy oral
Travere Therapeutics: Sparsentan FSGS PDUFA outcome (April 28, 2026) still not visibly resolved. Flagged as unverified for second consecutive week
Intellia lonvo-z: Full HAELO Phase 3 safety table at upcoming conference. Rolling BLA submission progress
United Therapeutics: Ralinepag NDA targeted H2 2026 (PAH). Tyvaso IPF regulatory path post-TETON-1
Seaport (SPTX), Hemab: First-week trading prints will signal whether the IPO window stays open or tightens
Have a great rest of your week and thanks for reading Biotech Blueprint!
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Cover image credit: https://dmpkservice.wuxiapptec.com/articles/5-an-overview-of-protac-technology-and-dmpk-research-strategy/ Example of PROTAC structure.