The U.S. Food and Drug Administration (FDA) is poised to conclude 2024 with a series of critical decisions on several novel drug applications, many targeting rare and genetic diseases, as well as notable cancer therapies. These decisions, expected in the coming weeks, could significantly impact the treatment landscape for a variety of conditions.
Ionis' Olezarsen for Familial Chylomicronemia Syndrome
Ionis Pharmaceuticals is awaiting the FDA's verdict on olezarsen, an investigational RNA-targeted therapy for familial chylomicronemia syndrome (FCS), with a decision due December 19. FCS, a rare genetic disorder affecting 1 to 13 per million people in the U.S., is characterized by elevated triglyceride concentrations due to a dysfunctional lipoprotein lipase enzyme. This leads to an inability to break down specific lipoproteins, increasing the risk of acute pancreatitis. Olezarsen aims to address the root cause of FCS by reducing the production of apoC-III protein, a key player in triglyceride metabolism.
The New Drug Application (NDA) is supported by data from the Phase III Balance study, which demonstrated a statistically significant 44% placebo-adjusted reduction in triglyceride levels after six months (p < 0.001).
Lexicon's Sotagliflozin for Type 1 Diabetes
Lexicon Pharmaceuticals is anticipating the FDA's decision on sotagliflozin as an adjunct therapy to insulin for type 1 diabetes, with a deadline of December 20. This follows a challenging advisory committee meeting. Sotagliflozin functions by blocking SGLT2 and SGLT1 proteins, which are crucial for sugar absorption in the kidney and gut. Phase III trials showed A1C reductions between 0.35% and 0.46% versus placebo, which Lexicon described as statistically significant.
However, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee raised concerns about the drug's risk-benefit profile, particularly in patients with mild kidney damage, requesting additional data.
AstraZeneca and Daiichi Sankyo's Dato-DXd for Non-Squamous NSCLC
AstraZeneca and Daiichi Sankyo are seeking approval for their anti-TROP2 antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) for adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). The FDA is scheduled to release its verdict by December 20.
The application is based on data from the Phase III TROPION-Lung01 study, which demonstrated a 37% reduction in the risk of disease progression or death compared to docetaxel. However, a subsequent readout indicated that Dato-DXd's overall survival (OS) benefit of 16% did not reach statistical significance.
Zealand's Glepaglutide for Short Bowel Syndrome
Zealand Pharma is seeking approval for glepaglutide, a GLP-2 analog, for the treatment of short bowel syndrome (SBS) in patients on parenteral support. The FDA's decision is expected by December 22. SBS is characterized by a shortened or damaged small intestine, impairing nutrient absorption. There are approximately 7,500 SBS patients in the U.S. dependent on parenteral support.
Glepaglutide aims to reduce the need for parenteral support. The Phase III EASE-1 study showed that twice-weekly glepaglutide significantly lowered the total weekly volume of parenteral support at 24 weeks compared to placebo. Nine patients on glepaglutide were able to completely wean off parenteral support.
Rhythm's Setmelanotide for Genetic Obesity
Rhythm Pharmaceuticals is seeking to expand the label for Imcivree (setmelanotide) to include children as young as 2 years with specific genetic forms of obesity. The FDA is expected to release its verdict by December 26. Imcivree, a melanocortin-4 receptor agonist, is currently approved for patients aged 6 years and older with obesity due to deficiencies in POMC, PCSK1, or LEPR, as well as for Bardet-Biedl Syndrome (BBS).
The expansion bid is supported by data from a Phase III study in pediatric patients, which showed that Imcivree lowered body mass index by an average of 18.4%.
Checkpoint's Cosibelimab for Skin Cancer
Checkpoint Therapeutics is resubmitting its PD-L1 blocker cosibelimab for metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC). The FDA has until December 28 to make a decision. The initial application received a Complete Response Letter due to issues at a third-party manufacturing facility, not related to the drug's safety or efficacy data.
Cosibelimab is supported by data from a pivotal trial demonstrating a 47.4% confirmed objective response rate (ORR) in patients with metastatic cSCC and a 54.8% ORR in patients with locally advanced disease.
Mirum's Chenodiol for Cerebrotendinous Xanthomatosis
Mirum Pharmaceuticals awaits the FDA's decision on chenodiol for the treatment of cerebrotendinous xanthomatosis (CTX), a rare metabolic disease, by December 28. CTX is caused by mutations in the CYP27A1 gene, leading to impaired cholesterol metabolism and accumulation of toxic byproducts. Chenodiol works by dissolving the buildup of toxic cholesterol.
The regulatory application is backed by data from the Phase III RESTORE trial, which showed that chenodiol significantly reduced bile alcohol levels and improved serum cholestanol concentrations.
BMS' Subcutaneous Opdivo for Multiple Cancers
Bristol Myers Squibb (BMS) is seeking approval for a subcutaneous formulation of its PD-1 blocker Opdivo (nivolumab), with the FDA expected to announce its verdict by December 29. Opdivo is currently approved for intravenous administration for various cancers. BMS is seeking approval for the subcutaneous version for all previously approved adult solid tumor indications.
The application is supported by data from the Phase III CheckMate-67T study, which demonstrated non-inferiority to the intravenous formulation in terms of serum concentrations and overall response rate in patients with advanced or metastatic clear cell renal cell carcinoma.
Neurocrine's Crinecerfont for Congenital Adrenal Hyperplasia
Neurocrine Biosciences is seeking approval for crinecerfont, a CRF1 antagonist, for congenital adrenal hyperplasia (CAH) in adults and children, with decisions expected on December 29 and 30. CAH is a rare genetic condition disrupting adrenal hormone balance. Current treatments involve glucocorticoids, which can cause complications at high doses. Crinecerfont aims to prevent excess ACTH levels and control adrenal androgens without the need for high-dose glucocorticoids.
Phase III CAHtalyst studies showed that crinecerfont treatment led to significant reductions in androstenedione levels in both adult and pediatric cohorts, allowing patients to taper their glucocorticoid doses.
