SAN FRANCISCO – Though a decision on Duchenne muscular dystrophy (DMD) drug Kyndrisa (drisapersen) is due any day now, Biomarin Pharmaceutical Inc. executives played down the U.S. market opportunity during their J.P. Morgan Healthcare Conference presentation, focusing instead on the market potential of the drug in Europe and highlighting the remainder of the pipeline, including presenting new phase II data for Pompe disease drug reveglucosidase alfa.

The FDA delayed the original PDUFA date of Dec. 27 for Kyndrisa, with a decision expected sometime this month, according to San Rafael, Calif.-based Biomarin.

Analysts generally remain cautious on drisapersen's approval, following a confusing advisory panel in November. Rather than voting on whether the exon 51-skipping drug should be approved, the Peripheral and Central Nervous System Drugs Advisory Committee was asked by the FDA to opine on the strength of two phase II trials and a single phase III trial used to develop the drug. The result was a meandering mix of questions about the design of the studies and concerns of using the production of dystrophin as a biomarker. (See BioWorld Today, Nov. 25, 2015.)

But Hank Fuchs, executive vice president and chief medical officer, noted that the advisory committee's thinking "may not be as black and white as appeared on the day of review."

Even with an FDA rejection, the company sees plenty of opportunity in other territories. In fact, Chairman and CEO Jean-Jacques Bienaime noted in his presenting remarks that the North American market for exon 51-skipping DMD comprises 2,000 patients, out of a total estimated 11,000 patients worldwide. In Europe, the opportunity is larger, with roughly 5,000 patients.

A decision from the EMA's Committee for Medicinal Products for Human Use is expected in the May-June time frame, Biomarin said. And the EMA has "shown it is not always in agreement with the FDA," Bienaime said, pointing to another DMD drug, PTC Therapeutics Inc.'s Translarna (ataluren), which targets nonsense mutation DMD and gained conditional EMA approval in 2014; Translarna has yet to gain approval in the U.S. (See BioWorld Today, May 27, 2014.)

Drisapersen was developed to increase the production of dystrophin, a complex protein with multiple functions. Biomarin has stressed in its primary data package for Kyndrisa a consistent evidence of efficacy across three placebo-controlled studies, including results showing a treatment effect at week 48 in the six-minute walk test, in a pooled population of 128 patients, with an improvement of 31.3 meters (p < 0.01). The treatment effect at week 48 in patients' ability to rise from the floor, in a pooled population of 125 patients, was an improvement in 25.8 meters (p = 0.015). Biomarin has contended that results from the phase III study, DMD114044, were consistent and provided support for the randomized phase II trials, since similar outcomes were documented across the three studies in patients with comparable baseline status.

Even if it clears the FDA, Kyndrisa could quickly face competition from eteplirsen, from Sarepta Therapeutics Inc., another exon 51-skpping DMD candidate, which has a PDUFA date of Feb. 26. Biomarin's advantage, however, would be its extensive experience commercializing in the rare disease space.

With or without Kyndrisa, however, the company is projecting revenue growth over the next few years. Bienaime said existing products should grow to sales of $1.5 billion by 2020. In 2016, Biomarin is anticipating more than $1 billion in revenues.

More billion-dollar opportunities could be coming down the line, among those Vimizim (elosulfase alfa), which received FDA approval for mucopolysaccharidosis Type IVA (Morquio A syndrome) in early 2014 and, according to executives, continues to ramp up nicely. (See BioWorld Today, Feb. 18, 2014.)

IMPROVED ERT FOR POMPE

Also advancing is reveglucosidase alfa (BMN 701), which Biomarin is hoping to position as an improved enzyme replacement therapy (ERT) to Pompe disease drug Myozyme (alglucosidase alfa) from Sanofi SA's Genzyme unit. Sales of Myozyme/Lumizyme totaled $720.3 million, according to Cortellis Competitive Intelligence.

Fuchs elucidated the potential advantage as relating to the addition of small protein IGF-2 as a tag to the molecule, allowing it to more tightly attach to the surface of the muscle cell than Myozyme, making it more effective. Even Pompe patients on Myozyme eventually lose muscle strength, leading to impaired function.

Biomarin is evaluating reveglucosidase alfa in the phase II INSPIRE trial. Interim data reported Monday from 24 patients who had been switched from Myozyme to reveglucosidase alfa showed that, at week 12, 18 patients on treatment with reveglucosidase alfa and who completed the study demonstrated respiratory muscle improvements with a mean increase of 2.2 points from baseline in percent predicted Maximal Inspiratory Pressure (MIP) and a mean increase of 3.1 points from baseline in percent predicted Maximal Expiratory Pressure (MEP).

At week 24, the patients completing the study also experienced a mean improvement of 26.1 meters in the six-minute walk test.

For the 14 patients who met eligibility at both screening and baseline, and who completed the study, a mean increase of 3.8 points from baseline in percent predicted MIP also was observed. The 18 patients completing the study showed a mean decrease of 3.7 points from baseline in percent predicted forced vital capacity (FVC), but were considered relatively unchanged from screening at -0.7 points in percent predicted.

Other pipeline programs include cerliponase alfa, for which Biomarin could file for approval around midyear, for use in CLN2 disease, a form of Batten disease. It also has pevgaliase, a next-generation phenylketonuria drug, with pivotal data expected later this quarter, and vosoritide, which is set to start a phase III trial in the fourth quarter.

Shares of Biomarin (NASDAQ:BMRN) closed Monday at $93.29, down $2.46.