September is turning out to be a busy month for the U.S. Food and Drug Administration. Here’s a look at this week’s schedule for PDUFA dates.
September is turning out to be a busy month for the U.S. Food and Drug Administration (FDA). Here’s a look at this week’s schedule for PDUFA dates.
Calliditas’ Nefecon for IgA Nephropathy
Calliditas Therapeutics, based in Stockholm, Sweden, has a target action date of September 15, 2021, for its New Drug Application for Nefecon for the treatment of IgA nephropathy (IgAN). The submission is based on positive results from Part A of the HefIgArd pivotal Phase III trial in 200 adults with IgAN. The study hit its primary endpoint of proteinuria reduction compared to placebo in addition to stabilization of EGFR at nine months. It also included data from the Phase II NEFIGAN trial, which also met the same primary and secondary endpoints as the NefIgArd study. It is being reviewed under Priority Review.
IgAN is a chronic kidney disease that has a slow progression over 10 to 20 years. It can lead to end-stage renal disease. It is the result of deposits of the protein immunoglobulin A (IgA) inside the glomeruli in the kidney. The glomeruli’s job is to filter waste and excess water from the blood and transport it to the bladder as urine. But the IgA protein buildup prevents this process, which can lead to blood and protein in the urine and edema (swelling) in the hands and feet. It is the most common cause of glomeruli inflammation.
The company filed for conditional approval with the European Medicines Agency (EMA) in May and is also being reviewed on an accelerated basis. The company indicates that if approved in Europe, it will be made available there in the first half of 2022.
At the company’s second-quarter report on August 19, they indicated they had significantly ramped up their precommercial operations in the U.S. as well as entered into “some key partnerships, in order to ensure that we are well positioned to initiate commercialization in Q4, subject to a positive outcome of the FDA approval process.”
Merck’s Belzutifan for von Hippel-Lindau (VHL) Disease-Associated Renal Cell Carcinoma
Kenilworth, NJ-based Merck had a target action date of September 15 for its NDA for its belzutifan for patients with von Hippel-Lindau disease-associated renal cell carcinoma (RCC), not requiring immediate surgery. The NDA was built on data from the Phase II Study-004 trial. In it, belzutifan demonstrated a confirmed overall response rate of 36.1% in that patient population.
On August 13, the FDA approved the drug under the brand name Welireg for this indication, as well as for adults with central nervous system (CNS) hemangioblastomas and pancreatic neuroendocrine tumors (pNET). The drug is an oral hypoxia-inducible factor-2 alpha inhibitor, the first such drug to be approved in the U.S. The drug decreases transcription and expression of HIF-2 alpha target genes linked to cellular proliferation, angiogenesis and tumor growth.
“Von Hippel-Lindau disease is a rare genetic condition for which there is no systemic treatment option available and is associated with a high risk of cancer development in multiple organs,” said Scot Ebbinghaus, Vice President, Clinical Research, Merck Research Laboratories, in March 2021. “In fact, up to 70% of patients with VHL develop renal cell carcinoma during their lifetime. This priority review validates the important progress we have made to expand and diversify Merck’s oncology pipeline with innovative, new therapeutic approaches. We look forward to working closely with the FDA to bring belzutifan to patients in need.”
The drug is also being developed for advanced RCC and other tumor types.
At the approval, Ramaprasad Srinivasa, Head, Molecular Cancer Therapeutics Section, Urologic Oncology Branch, National Cancer Institute (NCI), and principal investigator on the Cooperative Research and Development Agreement (CRADA) under which the NCI acted as a site in Study 004, stated, “The approval of a non-surgical treatment option is meaningful for helping patients with certain types of VHL-associated tumors. In Study 004, nearly half of all patients with VHL-associated renal cell carcinoma, as well as the majority of patients with VHL-associated central nervous system hemangioblastomas or pancreatic neuroendocrine tumors, who were treated with Welireg experienced a reduction of their respective tumor size. The FDA’s approval of Welireg marks an important step forward by introducing a systemic therapy that has the potential to improve the current treatment paradigm for patients with certain types of VHL-associated tumors.”
BeiGene’s Brunkinsa for Marginal Zone Lymphoma
Cambridge, Mass. and Beijing-based BeiGene has a target action date of September 19 for its supplemental NDA (sNDA) for Brukinsa (zanubrutinib) for adults with marginal zone lymphoma (MZL) who have received at least one previous anti-CD20-based therapy. It was also being reviewed under Priority Review status. Brukinsa is a BTK inhibitor. The sNDA was based on results from the Phase II MAGNOLIA trial in patients with relapsed or refractory (r/r) MZL.
Brukinsa was approved for another sNDA on September 1 for Waldenstrom’s macroglobulinemia (WM). It is approved in the U.S. for mantle cell lymphoma and WM, as well as for chronic lymphocytic leukemia (CLL) in other parts of the world.
