When the FDA approved the oral version of Wegovy as the curtain fell on 2025, the nod capped off a change-filled year at the agency that included unprecedented staff turnover, more flexibility for rare diseases, concrete moves to reduce animal testing and the arrival of several notable breakthrough drugs.
The GLP-1 pill also set the stage for a year of other groundbreaking approvals, including an oral Wegovy competitor, a potential blockbuster for high cholesterol and a first-in-class narcolepsy treatment.
Some of the year’s most anticipated approvals are based on brand-new, disease-modifying science while others, like oral GLP-1 advances, change the mode of administration for an existing medicine. But each has the potential to “open access to broader patient populations,” said Jon Roffman, head of pharmaceutical practice for healthcare and tech consulting firm ZS.
“The science is amazing and there’s a lot of great breakthroughs,” Roffman said, noting that the new therapies are focused on translating that science into helping patients get the most benefit while “removing friction for doctors and patients.”
Here are five potential high-profile FDA approvals worth watching in 2026.
Competition among oral GLP-1s
Oral administration is the new frontier in the massive GLP-1 market, and while Novo Nordisk won the FDA approval race with Wegovy, the competition for market dominance is just beginning.
Eli Lilly expects an FDA approval in March for oral orforglipron, which the FDA already tapped for its new National Priority Voucher program to speed drug approvals.
Although the Wegovy pill has a head start on the market, Novo has recently faced significant challenges, from losing its GLP-1 sales supremacy over Eli Lilly’s Zepbound to layoffs and the sudden appointment of a new CEO. While Lilly’s orforglipron didn’t result in as much weight loss as oral Wegovy in clinical trials, its added success with diabetes patients could give it an edge.
The oral GLP-1 market is expected to capture around 20% of the $80 billion obesity GLP-1 market by the end of the decade, and while a lot will depend on pricing (Wegovy’s self-pay price will be $149 monthly) the availability of these medicines in pill form is likely to broaden the market, said Bill Coyle, a chairperson and region managing principal at ZS.
“It’s an opportunity, potentially, for democratization across more countries and to offer more options for people living with obesity,” he said.
Another cholesterol-lowering option
Merck & Co.’s oral PCSK9 inhibitor enlicitide is another pill form of a currently available injection that could drive uptake for an entire drug category.
Although PCSK9 inhibitors, which lower LDL cholesterol have “incredibly good efficacy,” their uptake “hasn’t been amazing,” Coyle said.
That’s “potentially due to the fact that they are injectables and it's not normally what cardiologists or GPs are dealing with for cholesterol-lowering medications,” he said.
The first pill version of the medicine could change that paradigm, and has the potential to become a blockbuster. It’s also reportedly been tapped for the next round of the FDA’s National Priority Voucher program, according to Reuters.
“Having an oral PCSK9 also brings the opportunity for people trying to get their cholesterol under control where statins aren't working,” Coyle said.
Merck in November presented pivotal phase 3 trial results showing that enlicitide significantly reduced LDL cholesterol with a safety profile similar to placebo and high adherence rates.
A narcolepsy ‘gamechanger’
Takeda Pharmaceuticals’ oveporexton is a potential first-in-class oral treatment for narcolepsy that leverages orexins, which are neuropeptides secreted by neurons in the hypothalamus. Until now, they’ve mostly been used to treat insomnia.
But several drugmakers are testing the modality for narcolepsy with Takeda’s oveporexton leading the pack. The company is reportedly planning a late March FDA submission.
“What's exciting about oveporexton is that it doesn't target the symptoms, but it actually targets the root cause,” Roffman said.
Phase 3 pivotal studies for the oral orexin receptor 2-selective agonist showed statistically significant and clinically meaningful improvement in narcolepsy type 1 symptoms, which include excessive daytime sleepiness and a type of muscle weakness called cataplexy. It also had a good safety profile.
Despite these results, the drug could face hurdles once on the market for a rare condition that’s often under-diagnosed.
“Finding the right patients and getting the therapy to the right patients is going to require improvements in testing and improvements in the patient journey,” Roffman said.
He added that reimbursement could also prove challenging. But the drug’s potential advantages might carry more weight than any potential obstacles.
“It’s very exciting to see a therapy that's going to change the course of the disease state,” he said.
A first-in-class bispecific for tough-to-treat cancer
Epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer is among the specific types of the disease “that have been fairly resistant to standard immunotherapy,” Roffman said.
That makes Summit Therapeutic’s bispecific antibody ivonescimab, which achieved a 26% reduction in death risk, “promising” and “exciting” for Roffman.
Those results came from a trial conducted in China by Akeso, a Chinese company that struck a licensing deal with Summit to eventually market the drug across the globe. Ivonescimab has already been approved by China’s top regulator.
Roffman said the drug also improves outcomes when combined with chemotherapy.
“You actually see an enhanced effect relative to just giving the standalone therapies,” he said.
He added that although non-small cell lung cancer is the first potential indication, it could potentially treat GI and other solid tumors.
“We think this has the potential to impact a number of disease states in oncology going forward,” he said.
Despite this promise, Summit, which has no other marketed drugs, will still need to prove it can successfully launch a new therapy.
“They'll be facing very intense competition from some of the big players in oncology who have established PD-L1 therapies — the Mercks, the BMSs of the world — that are doing a lot in that space,” Roffman said.
A ‘curative-like’ outcome for Hunter syndrome
With a patient population of just 2,000 boys worldwide, Hunter syndrome is among the rarest of rare diseases and causes a range of debilitating symptoms, including breathing problems, heart disease, seizures, declining brain function, and bone and joint abnormalities.
“It’s a very high unmet need, but a very small segment of the population,” Roffman said. “There have not been really any good therapies. Twenty years ago was the last time we had a drug release, which was Elaprase, and that's a weekly infusion, which can be very hard for families with young boys.”
Enter Regenxbio and its gene therapy RGX-121. The treatment has the potential to be the first and only one-time, commercially available therapy that directly addresses the underlying genetic cause of Hunter syndrome. It received orphan drug, rare pediatric disease, fast track and regenerative medicine advanced therapy designations from the FDA and an advanced therapy medicinal products classification from the European Medicines Agency.
“It’s a one-time gene therapy [which] delivers the missing enzyme directly to the central nervous system and enables the patient to have somewhat of a curative-like outcome,” Roffman said. “It'll take time to prove the durability is there, but it'll be much more convenient than weekly infusions and have much better potential to help these young boys to thrive.”
Despite the promise, Roffman noted that significant post-approval hurdles lie ahead.
“Like other cell and gene therapies, I think we'll see similar price and access challenges,” he said. “You're talking about something that’ll probably only be able to be delivered by a handful of treatment sites around the country and of course something that’ll probably have a very high price tag. Analysts are expecting it to be in the multi-million dollars per patient.”
The company announced in August that RGX-121’s PDUFA goal date was extended from November 9 last year to February 8 in 2026.
