Hemophilia

Is the PDUFA delay for Stealth BioTherapeutics a canary-in-the-coalmine moment? Or is it an overblown one-off that signals little about disruption at the FDA? That’s the question seemingly on everyone’s minds after the FDA on Tuesday delayed a PDUFA date for Stealth’s new drug application. There weren’t safety or manufacturing concerns, the agency didn’t ask Stealth to conduct additional trials, and Stealth doesn’t know when a decision might get made. FDA Commissioner Marty Makary has pointed out that decision dates aren’t hard deadlines , but rather “target dates” the agency attempts to meet. That’s technically true: The law mandates that agency reviews meet a minimum of only 90% of the PDUFA dates it sets. “It’s not like missing a statutory deadline,” Patricia Zettler, an Ohio State professor who specializes in FDA law, told me this week. But the delay of Stealth’s PDUFA (as well as a delay for a post-CRL hearing from Vanda Pharmaceuticals) has people asking whether other stages of the regulatory process could be impacted. There are copious amounts of FDA work not tied to deadlines, like biomarker qualification programs , that could be slowed even if the FDA keeps largely hitting PDUFA dates. So far, most biopharma companies have said — both on earnings calls and in interviews with Endpoints — they aren’t seeing any impact on FDA reviews. And many recent PDUFA dates have been met without issues, including for Dupixent , Amvuttra , Sanofi’s RNAi drug for hemophilia and rare disease products from Amgen and J&J . Those applications coming through on time provide a significant counterpoint to the Stealth delay, Leerink analyst Daina Graybosch said. While Graybosch believes the agency will be affected by the layoffs (“it’s inevitable,” she said), it’s almost certainly too early to know how the changes at the FDA are going to affect US drug development and regulation. (Makary has argued that the regulator was overstaffed and inefficient before the cuts.) Graybosch didn’t follow the Stealth case closely, but she noted its exceedingly long development history and its drug having been previously rejected and delayed . “Blaming this on DOGE, I’m sorry, there’s so many things going on and ways and reasons to see risk,” Graybosch said. “Taking what happened at [Stealth] and reading into it more broadly feels alarmist to me.” But other analysts and FDA experts I spoke to agreed that the Trump administration’s healthcare staffing cuts are going against its stated goal of making government more efficient, and that firing hundreds of staff and slashing review teams will likely make the agency less effective at its job. “It may be too early to say things are chugging along just fine,” Zettler said. “Bigger questions are, ‘What about products that are earlier in development or are not as far along in their review process?’” —Max

With Sanofi's sale of consumer health unit Opella for 10 billion euros ($11.4 billion), expect Sanofi to step up its pursuit of "bolt-on" deals, chief financial officer Francois Roger said. Six months after entering talks with U.S. private equity firm Clayton, Dubilier & Rice (CD&R), Sanofi has closed a deal to sell a 50% controlling stake of its consumer health business Opella for 10 billion euros ($11.4 billion), the French biopharma powerhouse said on Wednesday.As for Sanofi’s next move with its fresh injection of funds, don’t expect a mega-merger any time soon.In its quarterly earnings presentation last week, in addressing the company’s plan after the sale of Opella, Sanofi Chief Financial Officer Francois Roger said that it will “explore external growth opportunities for bolt-on acquisitions.”With that, Roger cited the company’s deal last month for Dren Bio’s clinical-stage bispecific antibody, DR-0201. Sanofi paid $600 million upfront for the asset and pledged another $1.3 billion attached to launch and development milestones.“We have always been very active in the M&A space,” Roger said during the company’s quarterly call in January. “We may be a bit more in the near future due to the fact that we have a strong balance sheet.”Roger said last week that Sanofi’s “primary focus” with the added funding is to drive organic growth through R&D and other internal investments. Roger said it will bolster its “dividend policy” and enhance its share repurchase program.With the Opella deal, Sanofi will retain a 48.2% stake in the consumer healthcare outfit. Public sector investor bank Bpifrance will own a 1.8% stake in Opella and gain a seat on the board. CD&R gains a company that employs more than 11,000 people in 100 countries and operates 13 manufacturing sites and four innovation development centers. Opella is the third-largest over-the-counter business in the world, selling products such as Allegra, Doliprane and Dulcolax.With the move, Sanofi becomes a “pure-play biopharma,” it said, joining other companies in its sphere that have divested to focus on developing and marketing prescription drugs.Other drugmakers have made similar moves over the last several years, including Novartis, GSK, Johnson & Johnson and Pfizer. Sanofi’s largest acquisitions over the last few decades were a 2011 purchase of rare disease specialist Genzyme for $20.1 billion and an $11.6 billion buyout of Biogen spinout Bioverativ in 2018, which bolstered the company’s presence in hemophilia.In recent years, Sanofi has settled for smaller deals such as a $3.2 billion acquisition of Translate Bio in 2021, a $2.9 billion buyout of Provention Bio in 2023 and a $1.7 billion deal for Inhibrx in January to gain a rare disease drug.

Vertex Pharmaceuticals, Amgen and Jazz Pharmaceuticals are among companies that received a positive opinion from European regulators for drugs that are already in the US market. The European Medicines Agency’s human medicines committee (CHMP) said on Friday that it recommended the European Commission to give the go-ahead for six new medicines and 10 label expansions. Among the six new medicines was Vertex’s cystic fibrosis oral therapy called Alyftrek, which was approved by the FDA last December for the same indication. Amgen similarly got a CHMP nod for Tepezza in moderate to severe Thyroid Eye Disease. Tepezza was approved by the FDA for that condition in January 2020. Jazz also secured a positive opinion for its bile duct cancer antibody Ziihera, which was approved by the FDA in November last year. On Friday, the committee said it would re-examine its earlier decision to reject Eli Lilly’s Alzheimer’s drug Kisunla. It also recommends PTC Therapeutics’ drug, dubbed Sephience, to be used to treat hyperphenylalaninemia in patients with the metabolic disease phenylketonuria. The other CHMP medicine recommendations are for Italfarmaco’s therapy Duvyzat for Duchenne muscular dystrophy and Purpose Pharma’s Attrogy for ATTR amyloidosis. As for the 10 label expansions, the committee recommended extending two of Bayer’s drugs, including a new dose of Adempas, which is approved for pulmonary arterial hypertension, as well as extending the label for the hemophilia A drug called Jivi for children aged seven and above. Other label recommendations: The regulators also recommended the EC approve nine new biosimilar products, eight of which were biosimilars to Amgen’s denosumab, which is a treatment for rare bone disease.