In the next two weeks, the FDA will hand down its verdicts for three drug applications, including ones for multiple myeloma and hypoparathyroidism therapies.
The remainder of August looks sparse for the FDA, with just three target action dates over the next two weeks, including one for a bispecific antibody for multiple myeloma and another for an oral drug for an autoimmune liver disease.
Read below for more.
Ascendis Awaits Delayed Decision on TransCon PTH
Following a three-month extension in May 2024, the FDA is now approaching its August 14 deadline to render a verdict on Ascendis Pharma’s TransCon PTH (palopegteriparatide), which the Danish company is proposing for adults with hypoparathyroidism.
Patients with hypoparathyroidism suffer from impaired function of their parathyroid glands, which often manifests as headaches, muscle cramps and weakness. Once it progresses, hypoparathyroidism can result in long-term complications such as calcium deposits in the kidneys and brain. There are currently no dedicated therapies for the disease; patients are managed using high-dose calcium and active vitamin D therapy.
Designed to be administered via a once-daily subcutaneous injection, TransCon PTH is a long-acting prodrug of the parathyroid hormone. According to Ascendis’ website, it works by helping the body restore physiologic levels of the parathyroid hormone for 24 hours each day, in turn addressing the short- and long-term symptoms of hypoparathyroidism.
The FDA previously rejected TransCon PTH in May 2023 due to manufacturing concerns—though it flagged no problems with the drug’s safety and efficacy. Ascendis filed its resubmission in late 2023 with a decision originally set for May 14. However, following an additional data submission, the FDA pushed its decision date back by three months.
Gilead Gears Up for Potential Approval of Seladelpar in Primary Biliary Cholangitis
Gilead Sciences is developing the selective peroxisome proliferator-activated receptor delta (PPARδ) agonist seladelpar to treat the autoimmune liver disease primary biliary cholangitis (PBC). The FDA is expected to release its decision on or before August 14.
Designed to be taken orally, seladelpar is a potential first-in-class drug that works by blocking the PPARδ protein, which is a transcription factor central to several physiological processes, such as lipid metabolism and inflammation. Seladelpar’s mechanism of action could help regulate the immune response, in turn addressing a key underlying mechanism of PBC.
Seladelpar was originally developed by CymaBay, which in December 2023 filed an NDA for the drug candidate, backed by findings from the Phase III RESPONSE and ENHANCE studies, which together enrolled more than 500 PBC patients, as well as the long-term open-label ASSURE trial and Phase II data.
A few months later, in February 2024, Gilead snapped up CymaBay in a $4.3 billion acquisition agreement that gave it ownership over seladelpar.
In May 2024, amid the FDA’s ongoing review of seladelpar, Gilead published interim late-stage data from ASSURE, touting a significant reduction in pruritus in patients treated with the oral PPARδ blocker. Additionally, 37% of patients saw normalized levels of the alkaline phosphatase enzyme, a key liver biomarker.
Regeneron Anticipates FDA Verdict for Multiple Myeloma Candidate
By August 22, the FDA is expected to release its decision on Regeneron Pharmaceuticals’ investigational bispecific antibody linvoseltamab, which is proposed for the treatment of relapsed or refractory multiple myeloma.
Linvoseltamab works by targeting both the B-cell maturation antigen and CD3 protein, which is found on T cells. Through this mechanism of action, the bispecific antibody brings malignant B cells closer to T cells and promotes the body’s cancer-killing response. In December 2023, Regeneron released early data from the Phase I/II LINKER-MM1 study, showing that almost half of treated patients achieved complete response or better after a median follow-up of 11 months. Objective response rate was 71%.
However, the study also revealed several safety concerns with linvoseltamab. Adverse events Grade 3 or worse arose in 85% of patients, with the most common side effect being cytokine release syndrome. Fourteen participants, corresponding to 12% of the study sample, died due to treatment-emergent toxicities.
Regeneron released updated data from LINKER-MM1 in June 2024 affirming the high response rate associated with linvoseltamab, alongside promising progression-free and overall survival data.
Regeneron is also seeking European approval for linvoseltamab. The European Medicines Agency accepted its Marketing Authorization Application in February 2024.
