The opioid epidemic has killed hundreds of thousands of people in the U.S.. By the end of January, the FDA could approve a new, non-addictive pain drug experts hope will become a life-saving alternative for many.

Vertex Pharmaceuticals has spent decades in the incredibly challenging field of pain research. After much trial and error, the Boston-based biotechnology company finally found a drug it believed worked well enough to make it through clinical testing and FDA review. Several mid- to late-stage studies have shown this medication can alleviate different forms of pain, from the acute kind seen after certain surgeries to the chronic kind experienced by people with diabetes.

Importantly, though, the drug has yet to prove more effective than opioids. That, combined with opioids being cheap and widely reimbursed by insurers, raises questions about its ultimate value. Doctors say they aren't entirely sure what pain the drug will be the best suited to treat or how open payers will be to covering it.

That uncertainty has crept over to Wall Street as well. Vertex lost $15 billion in market value in December, when a study evaluating its drug against a type of lower back pain produced results that investors found lackluster. Many equity analysts still think Vertex has a blockbuster product on its hands, but there is at least one who argues the sales forecasts are overblown. — Jacob Bell

GSK could soon answer Pfizer in the two pharmaceutical companies’ ongoing market battle to develop better meningitis vaccines.

By Feb. 14, the FDA will decide whether to approve a shot dubbed MenABCWY. The vaccine combines components of two marketed inoculations, Bexsero and Menveo, to protect against the five most common strains of bacterial meningitis, an infection that in severe cases can cause deadly brain swelling.

If approved, the shot will represent another attempt to boost vaccine uptake against meningococcal disease, which remains low due to a complex vaccine schedule.

MenABCWY would also compete against rival Pfizer's Penbraya, a similar five-in-one shot that received FDA approval in 2023 for people between the ages of 10 and 25. GSK’s vaccine was tested in a similar age group.

Approval would also extend GSK and Pfizer’s rivalry in infectious disease. The companies have fought for market share with earlier meningitis shots and, more recently, with dueling RSV vaccines. But both have been challenged by dips in vaccine sales that have impacted earnings. — Delilah Alvarado

Alnylam Pharmaceuticals has developed five approved drugs in a track record of success that has cemented its as one of the industry’s most valuable companies. It still isn’t consistently profitable, however. An upcoming FDA decision on a drug called vutrisiran may finally change that. 

Alnylam already sells vutrisiran, as well as a predecessor drug called Onpattro, for a form of the genetic disease transthyretin amyloidosis that affects nerves. For years, though, Alnylam  has been trying to expand use of those therapies to people whose disease causes heart damage, or cardiomyopathy. The reward could be significant: Global Market Insights estimated earlier this year that the market for transthyretin amyloidosis treatments will surpass $11 billion by 2032, with the “cardiomyopathy” form accounting for the bulk of sales.

Alnylam came close with Onpattro, only to see the FDA reject its application in 2023. The company is hoping for a better outcome with vutrisiran, which, unlike Onpattro, was tested for long enough to tell whether it could extend lives and prevent hospital stays. Alnylam used a special voucher to speed up the FDA’s review, too. A decision is expected by March 23. 

Yet it’s unclear whether the FDA will convene experts beforehand to discuss Alnylam’s application — a concern of investors given the company changed its statistical analysis plan before reporting success, Leerink Partners analyst Mani Foroohar wrote in November. Even if vutrisiran is approved, its commercial prospects are uncertain, as Alnylam will have to compete with Pfizer and BridgeBio Pharma without clear evidence its drug is best. — Ben Fidler

Prader-Willi syndrome, a rare condition that causes insatiable hunger known as hyperphagia, has been difficult for drugmakers to target. Multiple high-profile programs have failed in clinical testing or been rejected by regulators, leaving the estimated 10,000 to 20,000 people in the U.S. who have the condition without any treatments to curb their relentless desire to eat. But the wait could soon end if the FDA approves Soleno Therapeutics’ diazoxide choline, or DCCR, by a March 27 deadline.

Soleno is making an unorthodox pitch to the FDA. Its drug — an extended-release form of a molecule, diazoxide, that’s used to treat low blood sugar — failed its main goal in a Phase 3 trial four years ago. Soleno claimed the results were skewed by the COVID-19 pandemic, arguing that data collected before and after March 1, 2020 differed vastly and that DCCR showed consistent benefits on secondary measures.

Discussions with regulators yielded an unusual plan to prove that case: A new portion was added to the study in which patients were randomized to either continue or stop receiving DCCR, and tested for hyperphagia levels over time. Soleno claimed success in that evaluation in Sept. 2023, leading to an approval application and a stock surge that lifted its market value past $2 billion.

The FDA delayed a decision in November, fueling skepticism among investors about Soleno’s chances. Yet some Wall Street analysts remain optimistic. In a note last year, Dae Gon Ha, of Stifel, noted how there is a “need of a ‘win’” for Prader-Willi patients and the agency’s willingness to be flexible in rare diseases. DCCR also hit statistical significance in a study the FDA endorsed and received a so-called Breakthrough Therapy designation from afterwards, indicating that “at face value, the data supports a meaningful effect,” wrote Baird analyst Brian Skorney in November. — Ben Fidler

By late March, an experimental hemophilia drug called fitusiran will finally get its day at the FDA, potentially concluding a long and winding development path.

Originally discovered by Alnylam, fitusiran is an RNA-based medicine that suppresses production of antithrombin, a protein that stops blood from clotting. A once-monthly shot, the drug could help people with either the A or B forms of hemophilia to reduce their dependence on the factor replacement therapies they use to prevent bleeds, regardless of whether they’ve developed an immune response, or “inhibitors,” to those treatments.

Sanofi has been involved with the program for a decade, acquiring some rights in 2014 and then gaining full ownership four years later. Over that time, fitusiran has overcome multiple obstacles. Clinical testing was twice suspended due to blood-clotting incidents, one of which resulted in the death of a study participant. Sanofi adjusted and tested lower doses and fitusiran eventually succeeded in trials. But the delays pushed fitusiran’s approval filing until 2024; Sanofi had previously anticipated a submission three years earlier.

In the meantime, other therapies for hemophilia A and B have been approved, including Sanofi’s own Altuviiio, Roche’s Hemlibra and a few gene therapies. These treatments offer patients more dosing flexibility and longer-lasting effects, raising the bar for new entrants.

In a presentation to investors last year, Sanofi left fitusiran off of a list of anticipated future blockbuster medicines. — Delilah Alvarado