8. Valoctocogene roxaparvovec

In preparation for a possible 2020 launch of hemophilia A gene therapy valoctocogene roxaparvovec, BioMarin has upgraded its gene therapy production capacity to 10,000 doses per year. (BioMarin)

Drug: valoctocogene roxaparvovec
Company: BioMarin Pharmaceutical
Used for: hemophilia A
Est. 2024 sales: $1.212 billion

While Roche struggled with its $4.3 billion takeover of Spark Therapeutics thanks to unexpected antitrust concern over the latter’s hemophilia gene therapy pipeline, a competitor has advanced with regulatory filings.

BioMarin Pharmaceutical submitted the application for its rival hemophilia A gene therapy, valoctocogene roxaparvovec, to the FDA at the end of 2019, just as the EMA accepted its package for accelerated review.

Industry watchers were confused by the U.S. Federal Trade Commission’s extra scrutiny around Roche-Spark because its SPK-8011 was not even the furthest hemophilia A gene therapy program in development—or the best, by the first look of it.

Three-year phase 2 data for BioMarin’s valrox showed that the one-time therapy maintained a median annual bleed rate of 0, or 0.7 on average, which translates into a reduction of 96% from patients’ study entry. Annual factor VIII usage also dropped to a median of 0 or an average of 5.5, versus 138.5 and 136.7, respectively, before treatment.

As for Spark’s SPK-8011, the drug led to a 94% reduction in annual bleeds among 12 phase 1/2 participants four weeks after infusion. But in August 2018, Spark’s stock slid at the news of some patients having experienced an immune response-related sharp decline in factor VIII levels. That slide basically opened the buyout window for Roche.

In May 2019, BioMarin unveiled that its phase 3 study also met the prespecified criteria for regulatory submissions. Now, as BioMarin’s applications are on EU and U.S. regulators’ desks, Roche/Spark is still in a lead-in study that tests traditional factor VIII replacement therapy for a future SPK-8011 phase 3.

RELATED: JPM: Watch out, Roche. BioMarin's gene therapy might bleed off the hemophilia A market

Expecting a possible launch in 2020, BioMarin has stepped up its manufacturing efficiency, having increased the capacity for its gene therapy facility in Novato, California, from about 4,000 doses a year to up to 10,000 per year.

The upgrade is important “because first-mover advantage in gene therapy is fundamental in a sense that every time you treat a patient that patient is off the market,” BioMarin Chairman and CEO Jean-Jacques Bienaime said at the annual J.P. Morgan Healthcare Conference.

Being able to produce 10,000 doses means the company can treat the entire existing severe hemophilia A U.S. patient population in two years—not that it will—ahead of a potential approval for SPK-8011, Bienaime explained.

Once approved, valrox will first compete for noninhibitor patients against Roche’s antibody drug Hemlibra, which has been rapidly stealing share from factor VIII treatments and contributed CHF 921 million ($950 million) to Roche’s top line in the first 9 months of 2019.

Citing a recent Citi survey of 60 U.S. hematologists, Bienaime showed that these physicians expect to switch 29% of Hemlibra patients and 34% of factor VIII patients over to gene therapy within a year.

EvaluatePharma predicts valrox could reach $1.212 billion in annual sales by 2024.

8. Valoctocogene roxaparvovec