After greenlighting 56 novel therapeutics in 2025, four notable applications continue to await the agency’s action after being delayed from the fourth quarter last year.
After a 2025 campaign that saw the FDA approve 56 novel therapeutics for cancer, neurological, rare diseases and more, the agency faces six major catalysts in the first quarter of 2026—four of which are carryovers from the fourth quarter of last year.
FDA approval and rejection rates were within historical norms, Jefferies analysts said in an investor note on Jan. 3, with the 46 Center for Drug Evaluation and Research nods trending down from 49 in 2024 and 10 Center for Biologics Evaluation and Research approvals remaining flat.
The regulator issued 19 rejections in 2025, with 15 of those coming from CDER, according to Jefferies. While CDER’s total is par for the course, the 4 complete response letters from CBER are “higher than historical standards,” the analysts wrote.
The PDUFA holdovers from Q4 2025 aren’t surprising given the FDA’s ontime approval rate has slipped recently. According to RBC Capital Markets’ 2026 RBC Global Biotech Outlook report, the FDA met its deadline around 75% of the time in the third and fourth quarters of 2025.”
Here, BioSpace looks at the major regulatory deadlines to watch for as 2026 kicks off.
Travere Seeks Filspari Expansion Into Rare Kidney Disease
After securing full approval in IgA nephropathy (IgAN) in August 2024, Travere Therapeutics is looking to expand its endothelin blocker Filspari into the rare kidney disease focal segmental glomerulosclerosis (FSGS). The FDA’s decision is expected on Jan. 13.
Affecting approximately seven people out of 1 million, FSGS is characterized by scarring at the kidney’s small blood vessel networks called glomeruli, in turn compromising the organ’s ability to filter waste out of the bloodstream. FSGS manifests as sudden weight gain, hypertension, swelling and, in severe cases, kidney failure. When left unchecked, FSGS can require emergency medical attention or become fatal.
Travere’s answer to FSGS is Filspari, a small-molecule dual-blocker of the endothelin type A receptor and the angiotensin II type 1 receptor, both of which play a role in glomerular injury.
The company initially pursued FSGS approval for Filspari in 2023, using data from the Phase III DUPLEX study, a double-blinded, parallel and active-controlled study with more than 370 participants. However, Filspari failed to significantly outperform Sanofi’s Avapro in terms of kidney function improvement, according to data published in November that year in The New England Journal of Medicine. The FDA in a Type C meeting said these data “are not sufficient to support an sNDA submission,” according to a December 2023 press release from Travere.
In its updated filing, accepted by the regulator in May 2025, Travere included findings from the Phase II DUET study, which found a more than twofold reduction in proteinuria—a key marker of liver damage—versus Avapro.
If approved, Filspari would be the first drug in the U.S. specifically indicated for FSGS.
REGENXBIO Gears Up for Hunter Syndrome Verdict After Delay
The FDA was initially scheduled to render a decision on REGENXBIO’s biologics license application for Hunter syndrome gene therapy RGX-121 by Nov. 9, 2025. However, after the biotech filed additional information to support the BLA, the FDA in August last year pushed back the target action date to Feb. 8, 2026.
At the time of the delay, the agency did not raise any issues with RGX-121’s data package nor identify any safety issues.
RGX-121 is an adeno-associated virus vector–based therapy designed to deliver a functioning copy of the human iduronate-2-sulfatase gene into the central nervous system. In patients with Hunter syndrome, also known as mucopolysaccharidosis II, this gene is mutated, leading to a defect in the enzyme of the same name that under healthy conditions helps breakdown certain cellular waste molecules.
As a result, patients with the disease develop its hallmark symptoms, such as developmental delays, growth abnormalities and abnormal accumulation of cerebrospinal fluid (CSF).
RGX-121 is backed by data from the Phase I/II/III CAMPSIITE study, which in February 2024 demonstrated an 86% median decrease in a key disease biomarker, called DS26, in the CSF. DS26 concentrations in CAMPSIITE approached normal levels, REGENXBIO said at the time.
Moreover, 80% of patients were able to stay off enzyme replacement therapy at the time of readout.
If approved, RGX-121 would be the first one-time therapy that directly addresses the underlying genetic cause of Hunter syndrome, REGENXBIO said in its August 2025 news release.
Ascendis Awaits Achondroplasia Decision for TransCon CNP
Also hit with a delay late last year was Ascendis Pharma, which announced on Nov. 26 that the FDA had extended its review for achondroplasia drug TransCon CNP, also known as navepegritide, following a major amendment to the company’s application.
A decision was originally scheduled for Nov. 30, 2025, but was pushed back to Feb. 28 this year.
Affecting one in 15,000 to 40,000 newborns, achondroplasia qualifies as a rare disease but is also the most common cause of dwarfism. Achondroplasia is caused by a gain-of-function mutation in the FGFR3 gene, which weakens the activity of certain cells that are important for bone development. Lying along this pathway is a hormone called C-type natriuretic peptide (CNP), which promotes bone growth by countering the effect of FGFR3.
Ascendis is looking to leverage this interaction with TransCon CNP, which helps bolster the level of this hormone in patients. Data from the Phase II ACcomplisH study, published in November 2023 in The Lancet, showed that TransCon CNP significantly improved annualized growth velocity by more than 1 cm per year on average as compared with placebo.
If approved, TransCon CNP will go toe-to-toe with BioMarin’s Voxzogo, which in November 2021 became the first-ever drug approved for achondroplasia. TransCon CNP is expected to be a strong challenger to Voxzogo, prompting BioMarin in its Q3 earnings call last year to withdraw its earnings target of $4 billion by 2027—a decision driven mainly by competitive threats to the drug.
Rocket Sets for Launch of Kresladi in Rare Genetic Disorder
On or before March 28, the FDA will render its decision on Rocket Pharmaceuticals’ Kresladi for the treatment of leukocyte adhesion deficiency-I (LAD-I).
With at least 300 cases reported worldwide, LAD-I is a rare, genetic disorder that primarily affects children. It is characterized by a dysfunctional immune system, manifesting as recurrent and severe infections. The disease is often fatal. Kresladi addresses LAD-I by delivering a functional copy of the ITGB2 gene, which encodes a crucial surface protein found on immune cells.
Pivotal Phase I/II data released in Oct. 2023 showed a 100% overall response rate 12 months after infusion. Rocket filed an application for FDA approval soon after but was rebuffed in June 2024 due to manufacturing concerns. The regulator accepted the company’s resubmission in October 2025.
A LAD-I expansion for Kresladi would give Rocket a much-needed win after a series of stumbles and reorganizations last year. In May, the FDA placed a hold on the biotech’s Danon disease gene therapy RP-A501 after a patient died due to acute systemic infection. The hold was released a few months later.
Then, in October, Rocket pulled its BLA for mozafancogene autotemcel, a gene therapy it was proposing for Fanconi anemia. The withdrawal was due to “business and strategic considerations,” the biotech said at the time, pointing to a prior restructuring initiative.
Rhythm Looks To Retain Groove After Delayed Decision in Rare Obesity
Rhythm Pharmaceuticals is looking to expand the label of its MC4 receptor agonist Imcivree to include acquired hypothalamic obesity, a severe and rare type of excessive weight gain tied to brain damage. The application is currently under extended FDA review, with a decision expected on March 20.
The hypothalamus, found at the base of the brain, is responsible for regulating hormones, including those involved in appetite and metabolism. Injuries to the hypothalamus can dysregulate these activities, which in some cases can lead to obesity. Patients with this type of hypothalamic obesity often suffer from type 2 diabetes, fatty liver disease and sleep problems.
Imcivree, administered via a subcutaneous injection, works by activating the MC4 receptor, which helps regulate hunger, satiety and energy expenditure. Data from the Phase III TRANSCEND study released in April last year showed Imcivree lowered body mass index by 16.5% at 52 weeks, versus a 3.3% gain in comparators taking placebo.
This benefit, Stifel analysts said in an April 7 note to investors, “is outstanding in a highly difficult-to-treat patient population.”
Imcivree was first approved in November 2020 for weight management in patients 6 years and older with obesity due to POMC, PCSK1 or LEPR deficiency, as confirmed by genetic testing. An expansion came in 2024, widening the age of applicability down to 2 years of age.
Third Time the Charm for Aldeyra’s Dry Eye Disease Drug?
Closing out this list is a drug that’s had a difficult regulatory road thus far: Aldeyra Therapeutics’ reproxalap, being proposed for the treatment of dry eye disease. An FDA review is ongoing and is set to end in a decision on or before March 16.
Aldeyra has been trying to get FDA clearance for reproxalap since 2023. In November of that year, the regulator rejected the drug, noting that Aldeyra had failed to sufficiently establish reproxalap’s benefits on key symptoms of dry eye disease. At the time, the agency requested “at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye.”
In its resubmission, Aldeyra provided data from a late-stage dry eye chamber study, showing that reproxalap significantly improved patients’ comfort levels. The FDA was again unimpressed, handing out a second rejection in April last year. Aldeyra had “failed to demonstrate efficacy in adequate and well-controlled studies,” the regulator said at the time and asked for another study.
Aldeyra filed another application in July 2025, buffing it up with data from “a single clinical trial that achieved the primary endpoint of reducing ocular discomfort.” The FDA was supposed to have released its verdict on Dec. 16, but asked for data from a field study that did not meet its primary endpoint. Topline findings in May 2025 were “numerically supportive” of reproxalap’s efficacy in dry eye disease, but failed to reach statistical significance.
To give the regulator time to evaluate the submission, reproxalap’s review was extended by three months.
