FDA advisory committee’s concerns

On November 24, 2015, the Peripheral and Central Nervous System Drugs Advisory Committee of the FDA (U.S. Food and Drug Administration) discussed clinical data submitted by BioMarin Pharmaceutical (BMRN) to support Kyndrisa’s (drisapersen) new drug application (or NDA). The data were based on three clinical trials that involved more than 300 patients.

FDA Committee Raises Concerns about Kyndrisa’s Efficacy, Safety

The above diagram shows the key findings of the FDA advisory committee based on submitted clinical data.


The committee observed that data from the three clinical trials have failed to establish the efficacy of Kyndrisa (drisapersen) in treating patients suffering with Duchenne Muscular Dystrophy (or DMD) Amenable to Exon 51 Skipping.

The first Phase 2 study, a partial blinded placebo-controlled study, was conducted on 53 patients who were either administered Kyndrisa or a placebo. Patients on Kyndrisa were exposed to two different dosing regimens: intermittent and continuous. In a placebo-controlled study, patients receiving Kyndrisa were compared with those receiving a placebo.

The primary endpoint or goal for this trial was a six-minute walk test (or 6MWT) after 25 weeks of Kyndrisa therapy. The American College of Rheumatology explains the 6MWT: “The six-minute walk test (6MWT) measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway.”

It was observed that patients on a continuous Kyndrisa dosing regimen showed statistically significant improvement in 6MWT compared to those on a placebo. However, efficacy could not be established for DMD patients receiving Kyndrisa intermittently.

The FDA advisory committee noted that the positive findings from the continuous arm were not substantiated independently. An additional Phase 2 study and a larger Phase 3 study also failed to establish Kyndrisa’s efficacy, thus leading to the verdict of inconsistent results.

Unblinded trials

The FDA preview team believes that both patients and investigators may have known whether they were administered Kyndrisa or a placebo. This is due to a higher incidence of obvious injection site outward reactions from injecting Kyndrisa. Since 6MWT is also related to the effort of the patient, the result may be affected if a patient and investigator are biased about the drug’s results.

Safety profile

The FDA committee is concerned about the safety profile of Kyndrisa. Adverse events such as renal injury, thrombocytopenia, vascular injury, and dermal toxicity were observed in clinical trials.

Keep in mind that it’s not obligatory for the FDA to agree to or act according to the committee’s findings when it decides whether or not to approve the drug. Most of the brokerage firms tracking BioMarin Pharmaceutical have projected the probability of Kyndrisa’s FDA approval at 50%. However, Baird analyst Brian Skorney notes that based on the evidence, the FDA may not approve the drug.

If Kyndrisa is not approved, it will negatively impact BioMarin’s share price. However, if it is approved, Kyndrisa will result in high profits for the company. This is similar to other rare disease drugs such as Alexion Pharmaceuticals’ (ALXN) Soliris, (eculizumab), Amgen’s (AMGN) Blincyto (blinatumomab), and Gilead Sciences’ (GILD) Zydelig (idelalisib).

Investors can participate in the upside potential of Kyndrisa and still avoid excessive company-specific risks by investing in the PowerShares QQQ ETF (QQQ). BioMarin Pharmaceutical accounts for about 0.28% of QQQ’s total holdings.

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