The FDA’s Complete Response Letters, Creating Investment Opportunities?

Yesterday, under Today’s Highlights, we posted that the U.S. FDA issued a Complete Response Letter (CRL) to Gilead Sciences (GILD) with regard to the New Drug Application (NDA) for filgotinib – the investigational treatment for moderately to severely active rheumatoid arthritis (RA), in collaboration with Galapagos (GLPG).

The FDA requested data from the ongoing MANTA and MANTA-RAy studies before completing its review of the NDA. The MANTA and MANTA-RAy studies assess whether filgotinib has an impact on sperm parameters. The Agency has also expressed concerns regarding the overall benefit/risk profile of the filgotinib 200 mg dose. 

BioMarin Was Also Issued a CLR from the FDA

The US FDA also issued the same unwelcome Complete Response Letter (CRL) for  BioMarin Pharmaceuticals (BMRN). It is unwelcome because the CLR does not bring news about approvals but rather about problems that need solving before granting approvals causing approval delays.  

The FDA CRL was to inform BioMarin that its Biologics License Application (BLA) for valoctocogene roxaparvovec gene therapy for severe hemophilia A is complete but not yet ready for approval in its present form.

The CLR contents were surprising not only to BioMarin, its scientists, officers and shareholders but also to the specialists who treat patients with hemophilia A, their patients and the patients’ families. All were convinced that the gene therapy product would be approved. They were all waiting for the day the scientific miracle cure was expected to be given the green light to reach the clinic.

Instead of celebrating the arrival of the gene therapy, they, instead, received an unwelcome CRL.

Why is BioMarin Surprised?

BioMarin and the FDA had agreed on the extent of data necessary to support the BLA. What the FDA introduced in the letter was a new recommendation requesting two years of data from the Company’s ongoing Phase 3 study to provide substantial evidence of a durable effect using Annualized Bleeding Rate (ABR) as the primary endpoint. The FDA’s newly raised recommendation was mentioned for the first time in its CRL. It asked the Company to complete the Phase 3 Study and submit a two-year follow-up of safety and efficacy data on all study participants. 

The FDA based its decision on the consideration that the Phase 1/2 study does not support the durability of the treatment’s effect. The last patient in the Phase 3 study will complete two years of follow up in November 2021.  

Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin, said, “We remain committed to the hemophilia community and to leading the way to the first-ever gene therapy for hemophilia A. 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 of its potential to redefine the treatment paradigm for people with hemophilia A.”

The application was based on the Phase 3 study interim analysis of study participants treated with the investigational product manufactured by the to-be-commercialized process and three-year data from the Phase 1/2 Study. The FDA had granted valoctocogene roxaparvovec Priority Review status, Breakthrough Therapy and Orphan Drug designations, of which the gene therapy product will keep the Breakthrough and Orphan Drug designations.

The ongoing valoctocogene roxaparvovethec clinical trials will continue while BioMarin is exploring next steps to obtain approval.

The European Medicines Agency’s (EMA) Marketing Authorization Application (MAA) for valoctocogene roxaparvovec is still on.   

About Hemophilia A

Hemophilia A is called Factor VIII deficiency, or classic hemophilia, is an X-linked genetic disorder caused by a defective Factor VIII, a clotting protein. Although it is passed down from parents to children, about 1/3 of cases are caused by a spontaneous mutation – a new mutation that was not inherited.

Approximately 1 in 10,000 people have Hemophilia A. 

  • Factor VIII protein helps clot the blood of hemophilia A patients who are at risk of potentially life-threatening bleeds from even modest injuries.   
  • People with the most severe form of hemophilia A often experience painful, spontaneous bleeds into their muscles or joints. 
  • Individuals with the most severe form of hemophilia A make up approximately 50 percent of the hemophilia A population. 
  • The standard of care for severe hemophilia A is a Factor VIII replacement infusions administered IV two to three times a week or 100 to 150 infusions per year. 
  • Despite these regimens, many people continue to bleed, resulting in complications including progressive and debilitating joints damage, which can have a major impact on their quality of life. 

Prohost Observations

Following the unwelcome FDA Complete Response Letter, BioMarin’s stock was decimated in trading today, dropping from around $118 to $76, before the news. This selloff of the stock demonstrates how overreacting and exaggerating investors respond to the FDA’s Complete Response Letters.

The same can be said about Galapagos following the FDA Complete Response Letter. That stock too was killed, trading now at $143.49, Down from $188.08.

What We Believe Will Happen

We believe that BioMarin’s gene therapy product, valoctocogene roxaparvovec for hemophilia A, and Galapagos’ and Gilead’s product, filgotinib for rheumatoid arthritis, will be approved.

We believe that the stocks will recuperate their losses and then become an opportunity to grab, especially because the losses were extremely exaggerated.  

With regard to Gilead, the stock is way undervalued.   


More FDA News…

The FDA delayed the Emergency Authorization for Blood Plasma Treatment.   

Prohost Biotech has No Comment about this.

Please read yesterday’s article about Gilead Sciences under Today’s Highlights.

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