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

SAN FRANCISCO—Roche bought Spark Therapeutics in 2019 mainly for its hemophilia gene therapy projects to complement FDA-approved antibody drug Hemlibra. But thanks to a manufacturing update by first mover BioMarin, there might be a much smaller market left when Roche arrives.

Previously, BioMarin said its gene therapy facility in Novato, California, could support about 4,000 doses a year. Now, after improvements in productivity there, the facility has capacity for up to 10,000 patients per year, BioMarin Chairman and CEO Jean-Jacques Bienaime said at the annual J.P. Morgan Healthcare Conference on Monday.

That is important, “because we want to be able to supply the gene therapy market as quickly as possible, 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,” he said.

For existing hem A therapies, including Hemlibra and traditional blood clotting factor VIII replacement treatments, patients need to receive injections at varied dosing intervals to reduce bleeding episodes. In contrast, gene therapy holds the promise to offer long-lasting effects with just one administration.

How significant is 10,000? By Bienaime’s calculation, it means the company can potentially treat the entire existing severe hemophilia A U.S. patient population in two years, “which is faster than our competitors can get their products approved on the market.”

Of course, covering all patients is impossible, and Beinaime said that’s not the plan. But it does demonstrate BioMarin’s ability to occupy market share, at least for the initial catch-up patient pool.

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Hemlibra is quickly becoming the new standard for hem A treatment, growing at the expense of Factor VIII replacement drugs. In the first nine months of 2019, it delivered CHF 921 million ($950 million) to Roche’s top line.

But a recent Citi survey of 60 U.S. hematologists cited by Bienaime showed that these physicians expect to switch 29% of Hemlibra patients and 34% of recombinant factor replacement patients over to gene therapy within a year after the latter becomes available. And in three years, the numbers could expand to 38% from Hemlibra and 45% from Factor VIII.

BioMarin Chairman and CEO
Jean-Jacques Bienaime (BioMarin)

BioMarin also has impressive clinical data to back its case. Before treatment with BioMarin’s valoctocogene roxaparvovec, patients in a phase 2 study experienced median annual bleed rates of 16.5 at the median, or 16.3 on average. Three years after a single injection, the drug maintained a rate of a median 0 and 0.7 on average.

Annual factor VIII usage also dropped to a median of 0 or average 5.5, versus 138.5 and 136.7 respectively before study entry.

“I think we have some would-be competitors portending they can do better than that—they can do negative bleeds?” Bienaime joked during a presentation at JPM.

Last May, BioMarin said an interim analysis found its phase 3 study also met the pre-specified criteria for regulatory submissions in the U.S. and Europe. With that study, BioMarin is trying to show valrox is superior to standard-of-care infusions with factor inhibitors. The trial recently finished enrollment and now boasts more than 130 patients, making it significantly larger than the hem A clinical trials its competitors have completed so far, Bienaime said.

The company has already filed those data for regulatory review in the U.S. and EU, with an FDA application acceptance expected in February and a possible approval within 2020.

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Roche's gene therapy effort is trailing behind BioMarin, as it’s only expecting readout from a lead-in observational study on traditional factor VIII replacement therapy by July to “assist in providing baseline information” for comparison to Spark’s SPK-8011 in a future phase 3.

Valrox’s price will certainly draw attention when the time comes, as gene therapies are notoriously costly. Without giving out a specific number, Bienaime said “it looks like the U.S. payers are somewhat comfortable with a price of around $2 million to $3 million per therapy.”

By the time it launches the product and begins official reimbursement talks with payers, BioMarin will have four-year durability data available. Given the current average annual cost for severe hem A patients in the U.S. is at about $700,000, four years of treatment would be $2.8 million, the CEO noted.

Hemophilia A is probably one of the most competitive gene therapy markets. Besides BioMarin and Roche’s SPK-8011, Sangamo Therapeutics and partner Pfizer recently shared positive results from the first two patients treated with SB-525 in a phase 1/2. UniQure, while in the lead in hemophilia B gene therapy, has only reported preclinical results for AMT-180 in hem A.

Overall, BioMarin expects 2020 revenue to hit about $2 billion, up from an estimated $1.7 billion in 2019, thanks to growth in its marketed drug portfolio and the launch of valrox, Bienaime said. In the long run, the company is aiming for $8 billion to $10 billion in 10 years.