FDA Updates for the Week of March 21, 2022

Keytruda gets another indication, the first targeted therapy for advanced prostate cancer is approved, BMS snags approval for Opdualag, the FDA misses PDUFA date for Reblozyl and issues CRLs for sintilimab and Natpara.

FDA approves Novartis’ Pluvicto for advanced prostate cancer.

The FDA has approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan) for the treatment of adult patients with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer (mCRPC).

Pluvicto (formerly referred to as 177Lu-PSMA-617) is the first FDA-approved targeted radioligand therapy for eligible patients with mCRPC that combines a targeting compound with a therapeutic radioisotope. Pluvicto is expected to be available to physicians and patients within weeks.

The FDA has also approved a complementary diagnostic imaging agent, Locametz, after radiolabeling with gallium-68 for the identification of PSMA-positive lesion. After radiolabeling, this imaging agent may be used to identify PSMA-positive lesions in adult patients with mCRPC through a positron emission tomography scan.

FDA approves Keytruda for advanced endometrial cancer.

The FDA has approved Merck’s Keytruda (pembrolizumab), as a single agent, for patients with advanced endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

At the same time, the FDA also approved the Ventana MMR RxDx panel, which was developed by Ventana Medical Systems and Roche Tissue Diagnostics, as a companion diagnostic device to select patients with dMMR in solid tumors that are eligible for treatment with Keytruda. The FDA previously approved the FoundationOne CDx from Foundation Medicine as a companion diagnostic device to select patients with MSI-H in solid tumors that are eligible for treatment with Keytruda.

BMS’s Opdualag snags approval for melanoma.

The FDA has approved Bristol Myers Squibb’s Opdualag (nivolumab and relatlimab-rmbw), a first-in-class treatment for adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma.

The fixed-dose combination of nivolumab and relatlimab, administered as a single intravenous infusion, will be available immediately.

FDA misses PDUFA date for BMS’ Reblozyl for rare blood disorder.

The FDA has extended the review of the supplemental biologics license application (sBLA) for Reblozyl (luspatercept-aamt) for the treatment of anemia in adults with non-transfusion-dependent (NTD) beta thalassemia to June 27, 2022.

The regulatory agency has extended the Prescription Drug User Fee Act (PDUFA) goal date by three months to provide time for a full review of the submission. The sBLA was based on safety and efficacy results from the pivotal phase 2 BEYOND study evaluating Reblozyl plus best supportive care in adults with NTD beta thalassemia.

Beta thalassemia is a blood disorder where low levels of hemoglobin lead to lack of oxygen throughout the body. It is caused by mutations in the HBB gene.

FDA issues CRL for Lilly’s sintilimab for first-line NSCLC.

The FDA has issued a complete response letter (CRL) for the biologics license application for sintilimab injection, a PD-1 inhibitor in combination with pemetrexed and platinum chemotherapy for the first-line treatment of people with nonsquamous non-small cell lung cancer (NSCLC).

The CRL includes a recommendation for an additional clinical study, specifically a multiregional clinical trial comparing standard of care therapy for first line metastatic NSCLC to sintilimab with chemotherapy utilizing a non-inferiority design with an overall survival endpoint.

This regulatory decision is consistent with the outcome of the Oncologic Drugs Advisory Committee Meeting in February. The ODAC had voted 14-1 vote in support for additional testing for sintilimab. In a statement after the meeting, Eli Lilly, one of the drugs developers, said it had hoped that its aggressive pricing strategy for the therapy would have swayed the committee.

But the agency does not take costs or pricing strategy into account when making decisions. Both the agency and the committee had objected to the reliance of studies only done in China. The agency cited in materials ahead of the meeting that multiregional trials are the preferred approach according to guidelines from the International Council for Harmonization and that most drug applications in the United States are based on multiregional trials. ORIENT-11, the trial used for this application, was conducted in China only, and regulators indicated the patients enrolled didn’t reflect the U.S. population. Patients in the study were young, predominantly male, with lower rates of smoking, and didn’t represent racial and ethnic minorities.

The FDA also indicated that if consulted ahead of the application, it would have advised company of the need for a trial with overall survival as an endpoint. In the ORIENT-11 trial, progression-free survival was the primary endpoint, with overall response rate and duration of response as secondary endpoints.

FDA issues CRL for Natpara for hypoparathyroidism.

The FDA has issued a complete response letter (CRL) in response to the Takeda’s prior approval supplement for Natpara (parathyroid hormone). Takeda had submitted its supplement in August 2021 to address the potential for rubber particulates in the product that led to the recall in September 2019. At the time, Takeda had recalled all doses of Natpara.

Natpara, a recombinant human protein, is a parathyroid hormone used to control low blood calcium in people with low parathyroid hormone blood levels. It is indicated for patients with chronic hypoparathyroidism who cannot be adequately controlled with standard therapy alone (calcium and vitamin D).

Natpara has not been commercially available since the recall, although some patients received the therapy free of charge through a special use program under the guidance of the FDA. The CRL delays the commercial return in the United States, the company said.