Biomarin Decision Might Add More Stress Than Put Pressure on the FDA to Approve Sarepta Drug

Biomarin Pharmaceutical’s (BMRN) decision to withdraw its DMD drug Kyndrisa™ (drisapersen) Marketing Authorization Application (MAA) from the European Medicines Agency (EMA) means more than pressuring the FDA to approve Sarepta’s DMD product eteplirsen.

As we see from Biomarin press release, its decision was based on several reasons, including the discussions at the May 2016 Committee for Medicinal Products for Human Use (CHMP) meeting, which clearly showed that the CHMP has already decided to issue a negative opinion. Motivated the decision also was the negative discussion with the FDA, in addition to the FDA Complete Response Letter the firm had received in January, which was a clear-cut rejection.

Regarding the approval of Sarepta’s drug eteplirsen, one must be aware of the reasons that led Biomarin to discontinue clinical and regulatory development of its DMD product Kyndrisa and its three other first-generation follow-on products, BMN 044, BMN 045 and BMN 053 for distinct forms of Duchenne muscular dystrophy. It is obvious that the exon-skipping approach did not produce the right dystrophin that can increase muscle mass and bring back strength to children’s muscles. Other reasons existed behind the failure of the drug to meet the endpoint of the six minutes walk and other trial endpoints.

Evidence about the drug’s failure and, maybe, the indirect gene editing failure approach are found in Biomarin press release, precisely in the statement that said, “The Company will continue to explore the development of next generation oligonucleotides for the treatment of Duchenne muscular dystrophy.” 

We can also guess it from what Jean-Jacques Bienaimé, BioMarin chairman and chief executive officer stated, “Our plan now is to invest in research of next generation oligonucleotides with the goal of making a safe and effective treatment available for boys with this devastating disorder.”

Such statements, in our opinion, puts more stress than pressure on the FDA while considering a compassionate approval for Sarepta’s DMD drug eteplirsen, which is produced through the same technique that created Biomarin drug Kyndrisa.

Kyndrisa is an antisense oligonucleotide that induces exon skipping to provide a molecular patch for dystrophin transcripts produced by certain mutated dystrophin genes. Exons are the parts of a gene that contain the instructions for generating a protein. In applicable cases, skipping an exon near the mutation allows for the production of a truncated but functional dystrophin protein.

On the other hand, the press release stated that BioMarin plans to work with physicians, patient groups, and regulatory authorities to develop a transition plan for those patients currently being treated with Kyndrisa, BMN 044, BMN 045 and BMN 053.

Could an FDA approval, or conditional approval of eteplirsen be of any help regarding this mission?

Could eteplirsen have a better safety profile than Kyndrisa?

In the Prohost Letter #396 posted yesterday on the Prohost Website, we wrote, “Compassion has become impossible to skip anymore in making it possible responding to the pressing demand for the urgent need for a DMD to be approved and marketed. Parents of DMD children, the people who learned about the DMD calamity, the DMD organizations, foundations and societies around the world and finally the U.S. Congress are all pressuring the FDA to rush into approving a DMD drug. The problem is that, before approving a DMD product compassionate basis, the FDA would want to make sure that the selected drug would serve the purpose of compassion, not misleading the activists, or further disappointing the suffering children.

Sarepta’s extremely small conducted clinical trials might not have been capable of demonstrating   eteplirsen advantages over all the drugs that the agency has rejected such as Biomarin DrugKyndrisa (drisapersen) and the drugs that are demonstrating promises in more advanced clinical trials. It is also evident also that the small early trial Sarepta has conducted cannot prove that eteplirsen will have a better outcome in late phase trials than other drugs that faltered in Phase 3 trials after the advanced trials have failed to replicate early trial successful results.

The delay in the FDA decision might be caused by the agency’s willingness to reexamine other firms’ drugs results and compare them to eteplirsen before it blindly approve Sarepta’s drug.”

Let’s wait and see what the FDA will come up with.

Regarding investment, Biomarin stated, “Notwithstanding this outcome for Kyndrisa in Europe, the Company continues to expect to achieve non-GAAP break-even or better in 2017.”

Indeed, Biomarin is ready, willing and able to confront and overcome bad news such as the failed DMD drugs.

The problem is that in case the FDA denies eteplirsen approval or conditional marketing authorization, we really don’t know how Sarepta could deal with such a huge for it problem.

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