BioMarin Receives FDA Complete Response Letter for Gene Therapy

August 27, 2020 - BioMarin Pharmaceuticals recently announced that FDA issued a complete response letter for the company’s biologics license application for a hemophilia A gene therapy.

In the complete response letter, FDA recommended an additional two years of data from the company’s ongoing Phase 3 study to provide additional evidence of a “durable effect” using annualized bleeding rate as the primary endpoint.

Additionally, FDA recommended that BioMarin complete the Phase 3 study and submit two-year follow-up safety and efficiency data on all study participants.

The differences between the Phase 1/2 study and the Phase 3 study limited FDA’s ability to rely on the Phase 1/2 study to support durability of effect, BioMarin said.

"We remain committed to the hemophilia community and to leading the way to the first ever gene therapy in hemophilia A," Jean-Jacques Bienaimé, chairman and chief executive officer of BioMarin, said in the announcement.

"We are surprised and disappointed that the FDA introduced new expectations for the first time in the Complete Response Letter.  We are confident in valoctocogene roxaparvovec gene therapy and its potential to redefine the treatment paradigm for people with hemophilia A."

The application was based on the company’s Phase 3 study interim analysis. This study was fully enrolled in November 2019 and the last patient will complete two years of follow up in November 2021.

The company stated that it plans to meet with FDA in the coming weeks to move forward with obtaining approval.

FDA Issues Complete Response Letter for Gilead’s RA Drug

Gilead recently announced that FDA issued a complete response letter for the company’s new drug application for filgotinib, an investigational treatment for moderate to severe active rheumatoid arthritis. 

In the complete response letter, FDA requested data from Gilead’s MANTA and MANTA-RAy studies before completing its review of the new drug application. These studies will uncover if filgotinib has an impact on sperm parameters.

FDA also voiced concerns over the overall benefit/risk profile of the filgotinib 200-milligram dose.

“We are disappointed in this outcome and will evaluate the points raised in the CRL for discussion with the FDA. We continue to believe in the benefit/risk profile of filgotinib in RA, which has been demonstrated in the FINCH Phase 3 clinical program,” Merdad Parsey, MD, PhD, chief medical officer at Gilead Sciences, said in the announcement.

The MANTA and MANTA-RAy study results are expected in the first half of 2021, Gilead said.

Currently, figotinib is under review by regulatory authorities around the world. But the European Medicines Agency’s Committee for Medicinal Products for Human Use recently recommended the drug in the EU for the treatment of adults with moderate to severe RA who have been unresponsive to other treatments.

Complete Response Letter Halts Progress for for Tricida’s Metabolic Acidosis Drug

Pharmaceutical company Tricida also recently announced that it received a complete response letter from FDA for its new drug application for veverimer, a metabolic acidosis treatment.

According to the complete response letter, FDA requested additional data beyond the TRCA-301 and TRCA-301E trials regarding durability of the treatment effect of veverimer on primary endpoint of serum bicarbonate and effect of the treatment on US population.

FDA also voiced concern as to whether the effect size would predict clinical benefit. But there were no safety, clinical, pharmacology/biopharmaceuticals, CMC, or non-clinical issues identified in the letter, Tricidia said.

“We have collaborated with the FDA on the Accelerated Approval Program for veverimer and while we are disappointed to receive this CRL, we are pleased that the FDA has provided helpful, specific comments and indicated their willingness to continue to work with us to pursue approval of veverimer,” Gerrit Klaerner, PhD, Tricida’s chief executive officer and president, said in the announcement.  

“We remain confident in the fundamentals of, and unmet medical need for, veverimer and we continue to conduct our confirmatory trial, VALOR-CKD.”

FDA provided various options for resolving the issues presented in the complete response letter.

For example, the agency indicated it is willing to meet with Tricida to discuss options for obtaining approval, including under the Accelerated Approval Program.

Therefore, Tricida noted that it will request a Type A meeting with FDA in the near future. Following the meeting, Tricida plans to provide an update on the next steps and estimated timing of potential resubmission of the NDA, which it expects to do in the fourth quarter.