IntellaTurn, LLC

🚨Note from Erin: The FDA policy landscape is shifting at an unprecedented pace. Below is a sampling of what we're tracking this week for our Regulatory TrendWatch newsletter.

➡️Learn more and subscribe (small team rates are available)

• Scoop by former Politico reporter Rachel Bade: FDA Commissioner Marty Makary is expected to get the ax in the coming weeks, according to two well-placed individuals familiar with the matter — the latest sign that Trump’s pre-midterm, house-cleaning isn’t over.

• Nothing is certain, these people said. And the president could always change his mind.

• But sources expressed confidence that Makary was serving on borrowed time, given all the enemies he’s made in the administration, feathers he’s ruffled within Trump’s coalition, and — especially — for upsetting the president personally.

• Read the scoop: The Inner Circle

• FDA Commissioner Makary has hit back anew at criticism that he and his agency have received in recent months over contentious drug decisions and mounting internal disarray.

• “I stand by the scientists at FDA,” Makary said in an interview with CNBC on Tuesday. “On my watch, we have not done corrupt sweetheart deals. What we have done is followed the science.”

• Much of the blowback against Makary, according to CNBC, stems from the agency’s controversial rejection of Replimune’s melanoma therapy RP1.

• The denial was due largely to Replimune’s insistence on using a single-arm trial to back its application, according to the FDA’s Complete Response Letter, which was made publicly available in line with the agency’s effort last July to release all rejection letters.

• Read the full story: Biospace

• Sanofi asked the FDA to pull its type 1 diabetes drug, teplizumab, out of FDA Commissioner Makary’s new Commissioner’s National Priority Review program.

• The move comes after acting CDER Director Tracy Beth Høeg disagreed with a staff decision to approve the drug.

• The agency missed its April 21 goal date to deliver a decision to Sanofi. Such decisions are typically made by career scientists.

• It is rare for a center director to become involved in scientific review of a single drug, and particularly a political appointee like Høeg. Makary recently said that he stands behind review teams, and that “disaster” occurs whenever political leaders overrule scientific staff.

• Read the report: STAT

• Agitation is a common Alzheimer’s disease symptom, manifesting as pacing and restlessness as well as verbal and physical aggression to family members and caregivers.

• The drugs used to quell these behaviors come with safety risks. An Axsome Therapeutics drug that works in a different way now has FDA approval for treating Alzheimer’s agitation, giving this product the opportunity to become a first-line treatment in this indication.

• The drug, Auvelity, was initially approved in 2022 for major depressive order in adults. The FDA decision expands use of the twice-daily pill to treating agitation associated with dementia due to Alzheimer’s.

• Auvelity has two main pharmaceutical ingredients, bupropion and dextromethorphan. This drug combination blocks the NMDA receptor and activates the sigma-1 receptor.

  • How this mechanism of action treats depression was not fully understood at the time of Auvelity’s initial approval and it’s also unclear exactly how it treats agitation.

  • Speaking during a conference call, Axsome CEO Herriot Tabuteau said hitting the NMDA and sigma-1 receptors is believed to modulate the function of neurotransmitters implicated in Alzheimer’s. (MedPage Today)

• A first-of-its-kind protein degrader just won FDA approval, marking a milestone for an accelerating drug class.

• But the landmark “PROTAC” drug for breast cancer may make a quiet entry into the market. 

• Vepdegestrant, which will be marketed as Veppanu, only modestly slowed disease progression in a phase 3 trial, with the clearest benefit in patients with ESR1 mutations, narrowing its market potential.

• The results from last March have reshaped strategy at Arvinas, which announced last May that it would lay off about a third of its workforce.

• Rather than commercializing the drug itself, the company and its partner Pfizer are seeking a third-party to take the treatment forward as it refocuses on earlier-stage programs. 

• Despite what may be a muted launch, the protein degrader field is gaining momentum. 

  • Companies like Novartis and Bristol Myers Squibb have inked deals in this space, and the bustle includes not only stand-alone degraders, but variations such as degrader-based ADCs, which is being pursued by several large pharma companies.

  • Roche struck a deal with C4 Therapeutics worth up to $1 billion to partner on so-called degrader-antibodies for two oncology targets.(PharmaVoice)

• Now, its share has rocketed to 25%, grouped around just a few drugs with the potential to be mega-blockbusters.

• The concentration in mega-blockbusters is at an all-time high, with just 54 blockbuster assets, or around 9% of the late-stage pipeline, projected to generate approximately 70% of total risk-adjusted peak sales.

• As might be expected, those assets have driven the predicted average forecast peak sales per asset to $598 million last year, compared to $510 million in 2024.

• Dr. Stan Crooke's nonprofit, n-Lorem Foundation, is building custom medicines for them, free of charge.

• His company, Ionis Pharmaceuticals, which he founded in 1989 after being fired from SmithKline, eventually won FDA approval for Spinraza, a breakthrough treatment for spinal muscular atrophy.

• His first wife, Nancy, died of a rare vascular disease in 1984 — the same kind of rare, hard-to-treat condition he now dedicates his work to.

• The foundation accepts no payment and covers the cost of drug design and manufacturing itself.

• Now he's betting that the same technology can scale all the way down to a single human being.