Last Week Tonight in BioPharma: Week of May 4th
Happy Mother's Day! This week: Cytokinetics, Makary (almost) out, Roche buys PathAI, and more!
Welcome back to Last Week Tonight in BioPharma (LWTB). What a week!
This week, Cytokinetics hit it big non-obstructive hypertrophic cardiomyopathy setting up strategic crossroads, FDA instability crops up once again with Marty Makary likely to be fired by Trump, and Roche takes a major step in AI.
All that and more below. Let’s get into it!
But before that….Happy Mother’s Day to all moms, grandmothers, and mother figures reading this! This day always brings my mind back to women’s health. Both how far we’ve come and how far we still have to go.
Over the last five years we’ve delivered several new treatments in women’s health (outside of oncology): Zurzuvae (2023), the first oral postpartum-depression treatment; Veozah (2023), the first non-hormonal hot-flash therapy; and Orilissa and Myfembree, the first new oral endometriosis drugs in over a decade. Women’s health VC funding hit a record $2.6 billion in 2024, up 50% year-over-year.
Yet despite these new advances, it is so clear we still have a long way to go. Endometriosis affects ~190 million women, takes nearly seven years to diagnose, and has no disease-modifying therapy. PCOS, the most common endocrine disorder in reproductive-age women, has zero FDA-approved treatments. There are several studies ongoing studying GLP-1s in this space, with hopefully positive data forthcoming. Uterine fibroids affect up to 80% of women by age 50 and up to 90% of Black women, yet for decades the default “treatment” was hysterectomy. Preeclampsia causes over 70,000 maternal and 500,000 fetal deaths annually, with the only treatment being delivery. Black women in the U.S. die from pregnancy-related causes at 3.5× the rate of white women. Two-thirds of Alzheimer’s patients are women. 80% of autoimmune-disease patients are women. Yet only ~6% of private healthcare capital targets women’s conditions.
We've made progress, but we're nowhere near where we need to be. Women's health is human health. Our industry has the the tools, obligation, and and alignment with financial interests to make even more progress over the next five years.
Now onto an interesting week in BioPharma.
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📡 PRESS RELEASE DECODER
What the press releases actually mean
Cytokinetics’ Aficamten Hits Both Endpoints in nHCM — First Positive Phase 3 in a Population With Zero Approved Therapies
📅 May 5 | 🏢 Cytokinetics ( CYTK 0.00%↑ ) | 💊 Aficamten (MYQORZO) | 🏷 Phase 3 Topline Data
Cytokinetics reported positive topline results from ACACIA-HCM, the pivotal Phase 3 trial of aficamten in symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM). The trial randomized 516 patients 1:1 and met both dual primary endpoints at Week 36: KCCQ-CSS improved by 3.0 points over placebo (95% CI 0.5–5.5, p=0.021), and peak VO2 improved by 0.67 mL/kg/min over placebo (95% CI 0.22–1.1, p=0.003). All key secondary endpoints also hit with high significance (p<0.001), including NYHA functional class improvement, composite exercise parameters, and NT-proBNP reduction.
Safety was consistent with the known cardiac myosin inhibitor profile. LVEF fell below 50% in 10% of aficamten patients versus 1% on placebo. Two patients on aficamten had serious adverse events of heart failure associated with low LVEF. Dose interruptions for LVEF <40% occurred in 3% of aficamten-treated patients. Completion rates were comparable between arms (88.4% vs 90.3%).
This is aficamten’s second Phase 3 win — the first was SEQUOIA-HCM in obstructive HCM, which supported the FDA approval of aficamten as MYQORZO for symptomatic oHCM (already approved in the U.S., EU, and China). Cytokinetics has signaled it will file a second sNDA for the nHCM indication based on ACACIA-HCM data. Full results are expected at an upcoming medical congress.
🧠 BPS Take: This is a genuinely important clinical result. The nHCM population, which represents roughly half the HCM population, has had no approved disease-modifying therapy. Cardiologists have had nothing to offer except symptom management and the assumption that without obstruction, the disease was pharmacologically harder to treat. ACACIA-HCM changes that completely.
Strategically, this puts Cytokinetics in a position BMS cannot match. If the nHCM sNDA converts to approval, aficamten becomes the only cardiac myosin inhibitor labeled for both obstructive and non-obstructive HCM, giving CYTK commercial opportunity across the full spectrum of HCM. Remember, BMS’ Camzyos (mavacamten) failed in the P3 ODYSSEY-HCM study, leaving this opening for CYTK to be first-to-market in nHCM. BMS is working on a new study to tackle nHCM with CAMZYOS, but they will undoubtedly be later to market, after spending $13B to acquire mavcamten from MyoKardia in 2020.
The question I keep coming back to: does a second Phase 3 win in the same disease space accelerate acquisition interest, or does Cytokinetics now have enough standalone value to stay independent? CYTK was a name I called out on my buyout list earlier in the year. They are sitting at just under $10B in market with a product that may get low single-digit billions in revenue. The BMS precedent of $13B may be where some acquirers anchor too, but CYTK may be able to garner more given their competitive edge. CYTK could make sense for a strong CV player like Novartis or AstraZeneca. Watch the BD chatter closely over the coming months.
FDA Agrees to Reconsider Ebvallo CRL — Pierre Fabre Gets a Path Forward After a Rejection That Didn’t Add Up
📅 May 7 | 🏢 Pierre Fabre / Atara Biotherapeutics ( ATRA 0.00%↑ ) | 💊 Ebvallo (tabelecleucel) | 🏷 FDA Type A Meeting / Regulatory Update
Pierre Fabre announced that the FDA has completed a Type A meeting on the Complete Response Letter (CRL) issued in January 2026 for tabelecleucel, an allogeneic, off-the-shelf EBV-specific T-cell immunotherapy for EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD). The meeting outcome provides a resubmission path — Pierre Fabre described the discussion as reaching an accord on the BLA path forward. Type A meetings are reserved for urgent matters, including disputes over CRL decisions, and the FDA’s willingness to engage at this level signals meaningful internal reconsideration.
Tabelecleucel targets an ultra-rare, frequently fatal malignancy in immunocompromised post-transplant patients who have failed rituximab. Unlike autologous cell therapies, it doesn’t require patient-specific manufacturing — a critical advantage in a population often too ill to wait for custom products. The original CRL was widely described as inconsistent with prior FDA guidance the agency had provided to the sponsor during development.
🧠 BPS Take: The FDA walking back a CRL like this is not normal, and continues along a pattern of FDA capriciousness we have seen under this administration. Type A meetings exist for urgent disputes, but the agency providing a clear resubmission path on a rejection that both the company and external observers described as contradicting prior guidance is genuinely odd.
This story matters on two levels. First, tabelecleucel is a an allogeneic, off-the-shelf EBV-specific T-cells for critically ill transplant patients with almost no alternatives. The original CRL was always hard to reconcile with the clinical and regulatory logic of the program.
Second, and more troubling, the same week Sanofi pulls Tzield from a priority review program citing political appointee interference, we have the FDA providing a resubmission path on a rejection that didn’t track with its own prior guidance. Pair that with other controversial decisions we’ve seen this year (e.g. Replimune, UniQure, Sarepta, etc.) and you have one of the most important regulatory agencies on shaky ground. More on this in Connecting the Dots.
Incyte Gets Jakafi XR Approved — Lifecycle Management Play With a Tight Window Before the Patent Cliff
📅 May 1 | 🏢 Incyte ( INCY 0.00%↑ ) | 💊 Jakafi XR (ruxolitinib extended-release) | 🏷 FDA Approval
The FDA approved Jakafi XR, a once-daily extended-release formulation of ruxolitinib, across all three approved indications: myelofibrosis (MF), polycythemia vera (PV), and graft-versus-host disease (GVHD). The existing twice-daily Jakafi remains on the market. The XR formulation is designed to maintain therapeutic exposure over a 24-hour dosing interval, with the rationale that once-daily dosing improves adherence in a chronic disease population.
Jakafi is Incyte’s largest commercial asset. In Q1 2026, Jakafi generated $758 million in U.S. net sales — annualizing to roughly $3 billion. The drug’s core patents are expected to expire around 2027-2028, creating significant near-term generic exposure. The MF treatment landscape has grown more competitive since Jakafi’s original approval: pacritinib, fedratinib, and momelotinib are all FDA-approved alternatives with differentiated profiles in specific subpopulations.
🧠 BPS Take: This is one of the purest forms of lifecycle management. I don’t say that dismissively. This is what brands close to the end of their exclusivity do. Spin up an extended release formulation or a new route of administration. That new offering has its own patent life that can extend beyond the LOE of the original formulation. Incyte’s bread and butter is Jakafi and its staring at an estimated 2028 patent cliff on a ~$5B product (including Novartis’ share of revenues).
Once-daily dosing is a tangible convenience benefit compared to immediate release (twice-daily) Jakafi, but brings it to parity with most of the other JAK inhibitors in the myelofibrosis and polycythemia vera space. The push here will come from the Jakafi commercial teams aiming to influence patient and docs to switch to the XR formulation over the two year window prior to Jakafi IR coming off patent. Incyte tried to give themselves more runway for this, but ran into regulatory issues during their first attempt at an XR formulation back in 2023. Payers may not automatically cover Jakafi XR over generic ruxolitinib once generics hit the market, unless they are getting a big discount on the back end.
I think the bigger question for me is why is everything in MF still a JAK inhibitor? Aside from the other JAK inhibitors that have been approved in this space, this XR formulation is the last major innovation the MF landscape has seen. I am digging into this curiosity in a forthcoming post for paid subscribers, so stay tuned.
🌐 CONNECTING THE DOTS
When the outside world meets biopharma
The FDA is Coming Apart — Makary Firing, Flavored Vapes, RFK’s SSRI Push, and What It Means for Drug Development
📅 May 4–8, 2026 | 🏢 POLICY/MACRO | 🏷 FDA Credibility Crisis
Monday, May 4: HHS Secretary Robert F. Kennedy Jr. announces the “MAHA Action Plan” at a Mental Health and Overmedicalization Summit, announcing federal initiatives to reduce SSRI antidepressant prescribing. The plan includes new Medicare/Medicaid reimbursement for clinicians who help patients taper off psychiatric medications, prescribing trend transparency, and provider training. Kennedy’s statement: “Psychiatric medications have a role in care, but we will no longer treat them as the default.” Kennedy has previously, without evidence, linked SSRIs to mass shootings and claimed withdrawal symptoms are worse than heroin.
Tuesday, May 5: The Wall Street Journal reports Trump directly pressured FDA Commissioner Makary to approve flavored e-cigarettes. Makary had been blocking authorization since a February memo indicated he needed more time to evaluate the science. The same day, Sanofi requests removal of Tzield from the FDA’s Commissioner’s National Priority Voucher (CNPV) program after CDER head Dr. Tracy Beth Høeg became directly involved in the review.
Wednesday, May 6: The FDA announces its first-ever authorization of fruit-flavored e-cigarettes — four products from a company called Glas with Bluetooth age-verification technology. The timing, coming immediately after Trump’s pressure became public, is impossible to ignore. Public health groups and a bipartisan group of senators (Durbin and Collins) criticize the decision.
Thursday, May 7: New York Post runs “Knives out for FDA head Marty Makary.” NBC reports Trump is considering firing him. The frustrations are multiple and overlapping: slow-walking flavored vape approvals, failure to release a promised mifepristone safety review before midterms (Bloomberg reported in December that Makary told officials to delay it), the UniQure Huntington’s gene therapy rejection that led to Vinay Prasad’s second ouster, and the Moderna mRNA flu vaccine application refusal that was reversed days later.
Friday, May 8: Two stories break simultaneously. CNN reports Trump has “signed off” on a plan to oust Makary, according to a senior administration official, though no formal dismissal has occurred and Trump told reporters “I’ve been reading about it, but I know nothing about it.” Separately, Reuters reports exclusively that Kennedy’s HHS officials explored whether they could ban specific SSRIs — including Zoloft, Prozac, and Lexapro — as Kennedy prepared his MAHA plan. HHS denies the report. Regulatory experts are uniform: the FDA cannot unilaterally ban approved medications without new safety evidence. The American Psychiatric Association considers SSRIs a first-line, evidence-based treatment for depression and “strongly objects to framing the nation’s mental health crisis as primarily a problem of ‘overmedicalization.’”
🧠 BPS Take: If you've been a regular BPS reader you won't be surprised by this volatile behavior from the FDA, but this week felt like it reached a new level. Three threads connect.
First, Makary blocked flavored vapes in February based on a scientific review he said needed more time, Trump pressured him directly, and the FDA reversed course within days of that pressure becoming public. Whether or not the flavored vape authorization is scientifically defensible, it sure feels like a science-based decision was reversed under direct presidential pressure, and that is not how the FDA is supposed to work. Yet another example of why we should consider making it a more independent body, like the Fed.
Second, Kennedy's HHS exploring an actual ban on specific approved SSRIs threatens to set a dangerous precedent if it happens. These are drugs backed by decades of clinical evidence and considered first-line treatment by every major psychiatric organization. There is an argument to be made for combatting overprescription, but an outright ban would likely do more harm than good. The FDA doesn't have the legal authority to unilaterally ban approved drugs without new safety evidence, and this would require formal safety review processes that take months or years, but the signal this exploration sends to the industry, that approved drugs could be targets of political campaigns, is profoundly destabilizing.
Third, CNN reports Trump has signed off on ousting Makary but hasn't formally acted, in part because there's no replacement lined up. There are already so many holes in the FDA after so much staff turnover, and if Makary goes, that's another major destabilizer to an already chaotic agency. It's not like we've seen a deep bench of competent operators in this administration either, and I am not too confident that whoever takes over will exceed an already low bar.
The through-line across all three is an FDA that has operated inconsistently in the face of direct political pressure from higher-ups, and the unpredictability at the review level is emblematic of that. When Sanofi exits a priority review program because a political appointee intervened in a way the company couldn't predict, when the Ebvallo CRL contradicts prior guidance, when Moderna's flu vaccine application gets rejected then un-rejected within days, and when the Commissioner himself may be fired for not approving consumer products fast enough, the review process itself stops being rule-governed.
BioNTech Cuts 1,860 Jobs and Closes Four Manufacturing Sites
📅 May 5 | 🏢 BioNTech ( BNTX 0.00%↑ ) | 🏷 Restructuring / Workforce Reduction
BioNTech announced the elimination of approximately 1,860 manufacturing positions — roughly 25% of its global workforce — and the closure of four facilities: Idar-Oberstein, Marburg, and Tübingen in Germany (closing by end of 2027) and a Singapore site (closing during 2026). All four were scaled up during the pandemic for mRNA vaccine production. BioNTech’s COVID vaccine revenues peaked at approximately €19 billion in 2021. The company is funding an oncology pipeline pivot on depleting reserves, with lead mRNA cancer vaccine programs BNT111 (melanoma) and BNT116 (lung cancer) in Phase 2 — neither generating revenue.
🧠 BPS Take: BioNTech rose to prominence on the back of its COVID-19 vaccine business. As has been the case for other COVID-19 drug makers in that space, sales have been on a steady fall. Declining demand warrants pairing back capital expenditures for that business segment.
BioNTech was always an Oncology company at its core. Modality agnostic and Oncology focused. They’ve built an impressive pipeline in that therapeutic area, spanning bispecific antibodies, mRNA vaccines, ADCs, and other modalities. COVID-19 always felt like they were in the right place at the right time. While layoffs and site closure are never smooth, this is probably the right long-term moved (despite the short-term pain) to reallocate resources towards its oncology business.
What I am curious about is who will take over the helm of this company and guide it during this new chapter, while all this restructuring is in the works? The founders are stepping out to run a new spinout and it feels like this should be quite an attractive job opportunity for an outsider. I’m sure the board has no shortage of interested candidates. BioNTech is set up well to be a pure play oncology growth story. It has multiple late-stage studies across a diversified set of assets with rather large market opportunities and is well capitalized to invest in its own commercial future and invest in novel early-stage bets.
💰 FOLLOW THE MONEY
Deals, dollars, and what they signal
Bayer Acquires Perfuse Therapeutics for Up to $2.45B — First Drug Deal in Years Targets the Glaucoma Adherence Problem
📅 May 6 | 🏢 Bayer ($BAYN.DE) / Perfuse Therapeutics (Private) | 💊 PER-001 (intravitreal implant) | 🏷 M&A — Acquisition
Bayer will acquire Perfuse for $300 million upfront and up to $2.15B in milestones. The deal’s centerpiece is PER-001, an intravitreal implant currently in Phase 2 for glaucoma and diabetic retinopathy. The implant blocks a protein that constricts blood vessels and contributes to ocular damage — a mechanistically distinct approach from existing treatments. In glaucoma, it’s being studied as a way to improve vision; in diabetic retinopathy, it targets retinal blood flow restriction. Perfuse reported positive Phase 2 data in both indications last year. This is Bayer’s first major drug company acquisition since 2021.
🧠 BPS Take: Bayer has been in need of something to revitalize the prospects of its drug business. They’ve been in restructuring mode under CEO Bill Anderson since his arrival, the pharma pipeline has been visibly thin, and Eylea’s biosimilar exposure was always going to require a pipeline answer. The deal structure is fairly sensible for Bayer. This sort of backloaded deal probably works out better for them given how much debt they are saddled with and litigation payment obligations. This doesn’t solve all their problems, but is a step in the right direction. Hopefully one day in the future they will take their medicine and break up their disparate businesses into separate entities.
Roche Acquires PathAI for Up to $1.05B — The Most Strategically Coherent AI-Pharma Deal This Year
📅 May 7 | 🏢 Roche ( $ROG.SW ) / PathAI (Private) | 💊 AI digital pathology platform | 🏷 M&A — Acquisition
Roche will pay $750 million upfront with up to $300 million in milestones for PathAI, an AI-powered digital pathology company. PathAI’s platform applies machine learning to analyze pathology slides for cancer diagnosis, biomarker identification, and companion diagnostic development. PathAI had raised approximately $255 million in venture funding. The acquisition positions Roche to integrate AI-driven pathology directly into its $16 billion diagnostics business (Roche Diagnostics, Ventana).
🧠 BPS Take: This is one of the most strategically coherent AI-pharma deals I’ve seen. Roche can integrate PathAI into a $16B diagnostics business that already sits at the intersection of oncology, companion diagnostics, and drug development. They are getting a data flywheel: every pathology slide processed through PathAI’s algorithm improves the model, which improves diagnostic accuracy, which improves clinical trial patient selection, which improves drug approval rates. Overtime this starts to look like a competitive moat that gets harder to replicate with every slide processed.
In oncology you sort of have two paths to success. Go broad or go narrow. Go broad is a lot harder to do, requires some luck, but in the end you can end up with a drug like Keytruda that is approved in nearly every solid tumor, or even Rituxan, which blanketed all of B-cell malignancies in its heyday. Narrow requires precision. This is your classic companion diagnostic or biomarker driven treatment strategy. Find the sub-segment that your drug really responds to and carve out a strategically advantageous position in that sub-segment. Revolution Medicines is doing this to great effect right now in mKRASG12 pancreatic cancer, but we have so many examples of building strong businesses with this strategy (ALK, EGFR, HER2, BRCA, etc.), and this PathAI deal seems like it will better equip Roche to take advantage of that.
GSK Licenses ALK7-Targeting siRNA from China’s SiranBio in Up to $1B Cardiometabolic Deal
📅 May 6 | 🏢 GSK ( GSK 0.00%↑ ) / SiranBio (Private, China) | 💊 SA030 (siRNA targeting ALK7) | 🏷 Licensing Agreement
GSK licensed global rights to SA030, an siRNA therapeutic targeting ALK7 (activin receptor-like kinase 7) for visceral fat reduction and cardiometabolic disease, from China-based SiranBio. Deal terms: $55 million upfront, up to $1 billion in milestones. SA030 is in Phase 1 with no public efficacy data. ALK7 inhibition has been shown preclinically to selectively reduce visceral adipose tissue — the metabolically harmful fat depot associated with cardiovascular disease, insulin resistance, and type 2 diabetes.
🧠 BPS Take: GSK’s cardiometabolic strategy is about being complementary to GLP-1s. Unlike their peers rushing to find the me-three/four GLP-1 to bring to market, GSK is telling you that they’re not interested in that. They’d rather be a combinatory partner to a GLP-1 backbone to enhance specific treatment effects. This ALK7 asset aims to more heavily target visceral fat, which a lot of science points to as one of the primary drivers of metabolic dysfunction. GLP-1s already help reduce visceral fat to a good degree, but perhaps adding ALK7 inhibition can further that. Notably there are still patients who don’t respond to GLP-1s or respond sub-optimally, and this sort MOA that works more on the thermogenesis and adipocyte targeting axis could be an effective alternative.
Back next week with more BioPharma strategy takes! Share this with a friend of colleague if you found it helpful.