The FDA’s year-end rush includes nine target action dates, mostly for rare disease and cancer therapies.
The FDA is ending 2024 with a bang. In the coming weeks, the regulator is set to decide on nine drug applications, many of them for rare and genetic diseases. The regulator will also release verdicts on a couple of notable cancer therapies.
Read below for more.
Ionis Awaits Verdict for RNA Medicine in Familial Chylomicronemia Syndrome
Ionis Pharmaceuticals is advancing the investigational RNA-targeted therapy olezarsen for the treatment of familial chylomicronemia syndrome (FCS). The FDA’s decision is due on December 19.
Diagnosed in between 1 and 13 per million people in the U.S., FCS is a rare, genetic disease involving elevated concentrations of triglycerides. People with FCS have a dysfunctional lipoprotein lipase enzyme and are unable to break down a specific form of lipoprotein, in turn suffering from a heightened risk of acute pancreatitis. Olezarsen addresses a core cause of FCS by decreasing the production of the apoC-III protein, which is involved in triglyceride metabolism.
To support its New Drug Application (NDA), Ionis filed data from the Phase III Balance study, which in April demonstrated a 44% placebo-adjusted drop in triglyceride levels after 6 months. This effect was statistically significant, with a p-value of less than 0.001.
Lexicon Eyes Type 1 Diabetes Approval for Sotagliflizon
After an overwhelming advisory committee meeting loss, Lexicon Pharmaceuticals now awaits the FDA’s verdict on its proposal to use sotagliflozin as an adjunct therapy to insulin for type 1 diabetes. The regulator’s deadline is December 20.
Sotagliflizon blocks the SGLT2 and SGLT1 proteins, both of which play central roles in the absorption of sugar in the kidney and gut. In three Phase III trials, add-on sotagliflozin elicited A1C reductions between 0.35% and 0.46% versus placebo—effects that Lexicon in a briefing document in October called “statistically significant benefits.”
However, external experts on the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee flagged uncertainties regarding sotagliflozin’s risk-benefit profile in this indication, and wanted to see more data for the drug, particularly in patients with mild or earlier-stage kidney damage.
Zynquista had previously been approved in Europe for type 1 diabetes, but Guidehouse Germany GmbH, which holds rights to the drug in the region, withdrew its marketing authorization in 2022.
Zealand Eyes Short Bowel Syndrome Nod for GLP-2 Analog
Zealand Pharma is proposing its investigational GLP-2 analog glepaglutide for the treatment of short bowel syndrome (SBS) in patients on parenteral support. The FDA’s decision is due on December 22.
SBS is characterized by a shortened or damaged small intestine, rendering patients unable to absorb enough nutrients from their food. According to Zealand, there are around 7,500 SBS patients in the U.S. who are dependent on parenteral support and typically suffer from symptoms such as diarrhea, weight loss and fatigue. If left unchecked, SBS can also lead to intestinal failure, which is associated with other severe complications, including liver and kidney failure.
Zealand’s glepaglutide is a long-acting GLP-2 analog that aims to eliminate the need for parenteral support in SBS patients. In the Phase III EASE-1 study, twice-weekly glepaglutide significantly lowered the total weekly volume of parenteral support at 24 weeks, as compared with placebo. Nine patients on glepaglutide were able to completely wean off parenteral support.
Rhythm Seeks Label Expansion for Genetic Obesity Injection
Rhythm Pharmaceuticals is proposing to expand the label for its injection Imcivree (setmelanotide) to children as young as 2 years with certain genetic forms of obesity. The FDA is expected to release its verdict by December 26.
Imcivree is a melanocortin-4 receptor agonist that won FDA approval in 2020 for chronic weight management in patients aged 6 years and up who have monogenic or syndromic obesity due to a deficiency in the pro-opiomelanocortin (POMC) peptide, the proprotein convertase subtilisin/kexin type 1 (PCSK1) enzyme or the leptin receptor (LEPR). In June 2022, Rhythm secured another FDA approval for Imcivree, this time in Bardet-Biedl Syndrome (BBS), a genetic disorder also characterized by obesity.
Currently, however, Imcivree is only indicated for patients aged 6 years and up. Rhythm’s expansion bid is supported by data from a multicenter, open-label Phase III study in 12 pediatric patients with obesity due to biallelic POMC/PCSK1 or LEPR deficiency, or a clinical diagnosis of BBS. Data showed that Imcivree lowered body mass index by an average of 18.4% in these patients.
Checkpoint Tries Again for Cosibelimab Approval in Skin Cancer
Following a previous rejection, Checkpoint Therapeutics is again seeking approval of its PD-L1 blocker cosibelimab, which it is developing for metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC). The FDA has until December 28 to release its decision.
Checkpoint is backing cosibelimab with data from a pivotal trial, which in January 2022 demonstrated a 47.4% confirmed objective response rate (ORR) in patients with metastatic cSCC. Interim data from the patients with locally advanced disease showed an ORR of 54.8%. Checkpoint used these data to file its first Biologics License Application for cosibelimab, which the FDA accepted in March 2023.
In December 2023, however, the regulator handed Checkpoint a Complete Response Letter, citing concerns around a third-party contract manufacturing organization. Importantly, the FDA did not identify issues with the biotech’s data package, nor did it flag problems with cosibelimab’s safety.
Mirum Awaits Approval in Rare Metabolic Disease
By December 28, the FDA is expected to release its decision on Mirum Pharmaceuticals’ oral drug candidate chenodiol for the treatment of the rare metabolic disease cerebrotendinous xanthomatosis (CTX).
Caused by mutations in the CYP27A1 gene, CTX is a progressive and underdiagnosed condition of impaired cholesterol metabolism that affects various organs. It is characterized by a dysfunctional sterol 27-hydroxylase enzyme, which leads to the pathologic accumulation of toxic byproducts such as cholestanol and bile alcohols. Common signs of CTX include chronic diarrhea, jaundice or bile flow interruption in newborns and neurological problems.
Mirum’s chenodiol, designed to be administered orally in tablet form, works by dissolving the buildup of toxic cholesterol. Its regulatory application is backed by data from the Phase III RESTORE trial, which found that chenodiol can significantly reduce bile alcohol levels in patients while also improving serum cholestanol concentrations.
BMS Eyes First Subcutaneous PD-1 Therapy With Opdivo Expansion
Bristol Myers Squibb is proposing a subcutaneous formulation of its PD-1 blocker Opdivo (nivolumab), for which the FDA is expected to announce its verdict by December 29.
Opdivo is currently approved for intravenous administration and is indicated for several cancers, including melanoma, non-small cell lung cancer and renal cell carcinoma. BMS is seeking to have a below-the-skin injection of Opdivo cleared for all previously approved adult solid tumor indications of its intravenous version.
To support its application, BMS filed data from the Phase III CheckMate-67T, which in October 2023 found the subcutaneous therapy to be non-inferior to the intravenous formulation in terms of time-averaged and trough serum concentrations at steady state, as assessed in patients with advanced or metastatic clear cell renal cell carcinoma. Subcutaneous Opdivo also achieved non-inferiority for overall response rate.
If approved, Opdivo would be the first subcutaneous PD-1 therapy on the market, giving it an important edge over its biggest competitor, Merck’s Keytruda (pembrolizumab), which is currently approved only as an intravenous therapy.
Neurocrine Seeks First New Congenital Adrenal Hyperplasia Approval in 70 Years
Neurocrine is proposing crinecerfont, an investigational CRF1 antagonist, for congenital adrenal hyperplasia in adults and children. The FDA is scheduled to release its decision on crincerfont’s capsule formulation on December 29 and oral solution formulation on December 30.
CAH is a rare, genetic condition that disrupts the balance of certain crucial adrenal hormones, including the adrenocorticotropic hormone (ACTH). CAH is currently managed using glucocorticoids, which at high doses can result in complications such as steroid excess, osteoporosis and diabetes. Crinecerfont is a selective blocker of the CRF1 receptor, allowing it to help prevent excess ACTH levels and control other adrenal androgens without the need for glucocorticoids.
In the Phase III CAHtalyst study, crinecerfont treatment led to significant reductions in androstenedione levels in both the adult and pediatric cohorts. In turn, patients were able to taper their glucocorticoid doses without compromising androstenedione control.
Correction (Dec. 9): This article was updated to remove AstraZeneca and Daiichi Sankyo’s Dato-DXd, the application for which in non-squamous non-small cell lung cancer was withdrawn last month. BioSpace regrets the error.
