FDA approvals roundup: Zogenix's Fintepla, Ultragenyx's Dojolvi, and Genentech's Phesgo
A weekly update on new drug approvals and indications from the FDA:
Fintepla gets the go-ahead for Dravet syndrome
Zogenix’s Fintepla (fenfluramine) has been approved for the treatment of seizures associated with Dravet syndrome in patients aged 2 years or older. The syndrome is a rare, life-threatening form of epilepsy.
The approval was based on findings from two clinical studies in 202 participants aged between 2 and 18 years, in which the change from baseline in frequency of convulsive seizures was measured. In both studies, children who received Fintepla had significantly greater reductions in the frequency of convulsive seizures, compared with those receiving placebo. The reductions were seen within 3-4 weeks of therapy initiation and remained generally consistent during the treatment periods of 14-15 weeks.
Fintepla is a Schedule IV controlled substance, carrying a boxed warning that it is associated with valvular heart disease and pulmonary arterial hypertension. It is available only through a restricted drug distribution program, under a risk evaluation and mitigation strategy (REMS) stipulating that prescribers and patients must comply with the required cardiac monitoring with echocardiograms to receive the therapy.
The application was granted priority review. The therapy received orphan drug designation.
Dojolvi picks up approval for rare genetic disorder
Ultragenyx’s Dojolvi (triheptanoin) has been approved for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD).
LC-FAOD are a group of rare, life-threatening genetic disorders in which the body is not able to convert long-chain fatty acids into energy. Dojolvi is a source of calories and fatty acids for these patients.
Safety data for the therapy came from 79 patients with LC-FAOD who received Dojolvi in 2 studies, an open-label, 78-week study with 29 patients (Study 1), followed by an open-label extension study (Study 2). In all, 24 patients from Study 1 continued into Study 2. Patients ranged in age from 4 months to 63 years. They received daily doses of Dojolvi for a mean duration of 23 months. The most common adverse reactions to the study drug included abdominal (60%), diarrhea (44%), vomiting (44%), and nausea (14%). A third study, a 4-month, double-blind, randomized-controlled study reported adverse reactions similar to those from the first two studies.
The agency previously granted the application rare pediatric disease and fast track designations. Ultimately, it assigned a standard review designation with a Prescription Drug User Fee Act target date of July 31.
Phesgo combo OK’d for home administration for HER2+ breast cancer
Genentech’s Phesgo (pertuzumab, trastuzumab, and hyaluronidase–zzxf injection) has been approved as a therapy for adult patients with metastatic HER2-positive breast cancer and for adults with early HER2-positive breast cancer, based on the results of FDA-approved companion diagnostic test.
Phesgo is initially used in combination with chemotherapy and could continue to be administered at home by a qualified health care professional once the chemotherapy regimen is finished.
The drug contains a fixed-dose combination of pertuzumab and trastuzumab with hyaluronidase. Its approval was based on the results of a noninferiority study in patients with HER2-positive early breast cancer showing that the drug’s efficacy and safety were comparable with IV pertuzumab and IV trastuzumab. Administration-related reactions were higher with Phesgo because of the subcutaneous route of administration.
“As part of the FDA’s ongoing commitment to address the novel coronavirus pandemic, we continue to keep a strong focus on patients with cancer who constitute a vulnerable population at risk of contracting the disease. At this critical time, we continue to expedite oncology product development. This application was approved about four months ahead of the FDA goal date,” said Richard Pazdur, director of the agency’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the Center for Drug Evaluation and Research.
Bavencio gets new indication for urothelial carcinoma
EMD Serono/Pfizer’s Bavencio (avelumab) has received an expanded indication for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line, platinum-containing therapy. It is the first approved immunotherapy to show significant improvement in overall survival in the first-line setting.
The application originally received breakthrough therapy designation and was granted priority review, which was completed under the real-time oncology review.
The human anti-programmed death ligand-1 antibody has a previous approval for locally advanced or metastatic UC that has progressed during or after platinum-containing chemotherapy. It has also been approved in combination with axitinib for the first-line treatment of patients with advanced renal cell carcinoma, and for treating Merkel cell carcinoma in adults and pediatric patients older than 12 years and older with metastatic disease.
Keytruda expanded for incurable CRC, cSCC
Merck’s Keytruda (pembrolizumab) has received two expanded indications, one, as a first-line treatment for patients with unresectable or metastatic microsatellite instability-high or mismatch repair deficient colorectal cancer, and a second, for treating patients with incurable recurrent or metastatic cutaneous squamous cell carcinoma (cSCC).
The approval for CRC was granted less than a month after the company submitted a supplemental biologics license application (sBLA) based on results from the KEYNOTE-177 trial. It is the first single-agent, anti-PD-1 therapy approved as a first-line therapy for these patients.
The sBLA was reviewed under the agency’s real-time oncology review pilot program. Review was also done under Project Orbis, which allows for concurrent submission and review of oncology drugs among international partners. For this application, the agency is collaborating with the Australian Therapeutic Goods Administration, Health Canada and Swissmedic on their ongoing review of the application.
The extended approval for cSCC was based on findings from the KEYNOTE-629 trial.
RAPS: First published in Regulatory Focus™ by the Regulatory Affairs Professionals Society, the largest global organization of and for those involved with the regulation of healthcare products. Click here for more information.