As this week’s FDA Action Alert emphasizes, not everything goes as planned with the U.S. FDA. With three PDUFA dates, two of them ran into issues. Read on to find out more.
As this week’s FDA Action Alert emphasizes, not everything goes as planned with the U.S. Food and Drug Administration (FDA). With three PDUFA dates, two of them ran into issues. Read on to find out more.
Merck’s Keytruda as Neoadjuvant and Adjuvant Treatment in TNBC
Merck has a target action date of March 29, 2021, for its blockbuster checkpoint inhibitor Keytruda (pembrolizumab) for patients with high-risk early-stage triple-negative breast cancer (TNBC), in combination with chemotherapy as neoadjuvant treatment, and as a single agent as adjuvant treatment after surgery. The standard review application was based on data from the Phase III KEYNOTE-522 clinical trial.
On February 9, 2021, the FDA’s oncology advisory committee met to discuss the submission and essentially indicated they didn’t believe the drug was ready to be approved for this indication. The 10 cancer experts voted unanimously that the company should wait for longer-term data from KEYTRUDA-522 before asking the FDA to approve it in these settings.
Aveo’s Tivozanib for R/R Renal Cell Carcinoma
AVEO Oncology had a target action date of March 31 for its tivozanib for relapsed or refractory renal cell carcinoma (r/r RRC). The agency approved the drug on March 10.
The NDA submission was based on the company’s pivotal Phase III TIVO-3 trial, comparing tivozanib to sorafenib in third and fourth-line RCC, including results the company presented at the American Society of Clinical Oncology 2020 Virtual Scientific Program. It is also supported by three additional trials, including an active comparator-controlled Phase III study, TIVO-1, and a placebo-controlled Study 201 in first-line RCC.
Tivozanib (Fotivda) is an oral, once-daily, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) discovered by Kyowa Kirin and approved for adults with advanced RCC in EU, the UK, Norway, New Zealand and Iceland. It is a potent, selective inhibitor of all three VEGF receptors with a long half-life.
“Today’s approval of Fotivda provides a new tool for treating patients with kidney cancer who have relapsed or become refractory to two or more prior systemic therapies,” said Brian Rini, chief of Clinical Trials at Vanderbilt Ingram Cancer Center and principal investigator of the TIVO-3 trial. “With advances in RCC treatment, patients are living longer, increasing the need for proven, well tolerated treatment options in the relapsed or refractory setting. The TIVO-3 study is the first positive Phase III study in RCC patients who received two or more prior systemic therapies, and also the first Phase III RCC study to include a predefined population of patients who have received prior immunotherapy, the current standard of care in earlier-line treatment. With this approval, I believe Fotivda represents an attractive intervention, and expect it to play a meaningful role in the evolving RCC treatment landscape.”
Acadia’s Nuplazid for Dementia-Related Psychosis
Acadia Pharmaceuticals has a target action date of April 3 for its supplemental New Drug Application (sNDA) for Nuplazid (pimavanserin) for dementia-related psychosis. The drug is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors. It is already approved for hallucinations and delusions associated with Parkinson’s disease psychosis.
On March 8, Acadia announced they had received notice from the FDA on March 3 that as part of the agency’s ongoing review of the sNDA, it had identified deficiencies that would not allow discussion of labeling and post-marketing requirements at that time. That notification did not reflect a final decision on the information under review.
The company stated that the notice by the FDA did not specify deficiencies and there was at that time no clarification. It plans to work with the agency to find out what the problems were and to resolve them.
