📉 Alnylam was one of biopharma’s biggest mysteries in the first half of the year. Although M&A was up, IPOs came back with record-breaking force, and the XBI nearly set an all-time high, Alnylam’s stock price was down about 30% from the start of 2026 through the beginning of this week. The drop came despite a largely successful 2025, when the company won a crucial label expansion for Amvuttra and made a profit for the first time in its 20-plus-year history. Max Gelman took an in-depth look at Alnylam’s 2026 troubles here. 

The company’s slump resulted largely from two things, analysts said. First, while Amvuttra had impressive sales numbers when it launched in its new indication, patient use appeared to slow toward the end of last year. But in July, a surprise Phase 3 failure for Ionis and AstraZeneca’s competing drug called Wainua raised concerns about Amvuttra’s staying power in the first-line setting compared to similar drugs. Some investors also began to question the potency of the experimental drug nucresiran, which Alnylam has positioned as an eventual Amvuttra successor.

Then, this week, Alnylam’s earnings report only fanned the flames for skeptics. The drugmaker lowered its full-year sales projection for Amvuttra by about $200 million while proactively playing defense in the wake of Wainua’s Phase 3 failure. The revision came with a seeming admission that Alnylam had misjudged Amvuttra’s market, specifically for patients in the second-line setting where demand fell in the first half of the year. 

“With the benefit of hindsight, it is now clear that a greater-than-understood proportion of early second-line volume growth was driven by pent-up demand from patients who are waiting for a new treatment option,” Alnylam CFO Jeff Poulton said on the company’s earnings call. Alnylam’s stock price closed about 30% lower on Thursday, a one-day drop that wiped out more than $10 billion in market cap. Read more here. 

📊 More than a dozen other pharma companies reported their second-quarter earnings this week. Here are the highlights: 

• AstraZeneca announced several pipeline updates, including a Phase 3 win for its stomach cancer candidate sonesitatug vedotin, albeit with a caveat. But it also revealed subpar results for Ultomiris in a rare disease, setbacks for Imfinzi and four discontinuations in its early-stage pipeline. CEO Pascal Soriot told the press on Monday that the company is looking to use AI to help boost the likelihood of success for its late-stage candidates.
• Takeda, Regeneron, Sanofi and Bristol Myers Squibb also announced program cuts as part of their quarterly updates.
• Just over six months into his tenure as CEO of GSK, Luke Miels revealed a three-year blueprint to cut costs and propel R&D.
• Biogen said its Eisai-partnered Alzheimer’s drug Leqembi recorded $184 million in global sales in the second quarter — the best since its launch three years ago.
• Sanofi booked over €1.03 billion in impairment charges in the second quarter, largely due to an eczema drug termination. It also teased a potential expanded collaboration with Regeneron for Dupixent follow-ons.
• Ipsen has its eyes trained on more M&A — and has €2 billion worth of “firepower” to do it.
• Moderna said it will need another norovirus season to adequately test the efficacy of its vaccine.

🤝 As IPOs have come back in vogue, so too have reverse mergers. This week, two biotechs took this alternative route to the public markets: Caldera Therapeutics and Vidya Therapeutics. The deals come as part of a reverse merger spree accounting for more than a dozen biotechs that have skirted the traditional IPO path. Read more from Kyle LaHucik here. 

Caldera had planned to raise a Series B in the second half of this year, but once the public markets started popping off this spring, the startup adjusted its financing plans and began thinking about an IPO, Caldera’s CBO Aaron Pelta told Kyle. Ultimately, Caldera wanted to move fast. It’s vying for a lane in the competitive TL1A field — but with a bispecific approach that tacks on another popular target of IL-23 (think AbbVie’s Skyrizi). Caldera inked a $278 million private placement along with the merger.

Vidya, meanwhile, is developing a BTK inhibitor that was originally discovered at Gossamer Bio and then acquired. The program, called VT-7208, will enter Phase 2 trials in food allergy and chronic spontaneous urticaria in the second half of this year. Vidya forged a $200 million private placement and will keep the name and ticker of its public shell, Processa Pharmaceuticals.

🔎Capricor Therapeutics and Replimune faced tough questions during advisory committee meetings this week. The companies had previously gotten rejections under former FDA chief Marty Makary, and cautiously hoped that new agency leadership could mean new flexibility.

The FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee ultimately voted against Capricor’s deramiocel, a therapy intended to slow the decline in cardiac function in patients with Duchenne muscular dystrophy. The committee’s vote sided with FDA reviewers who had maintained that deramiocel had failed to show significant efficacy, Zachary Brennan reported. Steven Pavlakis, a panel member and the chief of pediatric neurology at SUNY Downstate Health Sciences University, said the data backing the therapy are “very fragile” and it’s difficult “to say there’s a real effect.”

A day later, the same committee voted 10 to 3 in support of Replimune’s advanced melanoma treatment. The vote ran contrary to the conclusions of FDA staff reviewers who believed the company faltered in its study design, producing data that couldn’t be interpreted. Ultimately, most of the advisors felt that the data were meaningful enough in a patient population with few options that it was worth supporting, Max Bayer reported.

🧬Former Tessera Therapeutics CEO Michael Severino replaced Sarepta’s longtime leader Doug Ingram on Tuesday. Sarepta’s stock price is down nearly 90% compared to the start of 2025, and its leadership faced questions last year over transparency and credibility after failing to disclose a patient death on a gene therapy program for limb-girdle muscular dystrophy. But Severino said he’s looking toward the future. The chief executive is joining ahead of several upcoming milestones that could decide the company’s future trajectory. Read more here from Lei Lei Wu.