BioMarin says hemophilia A gene therapy data 'encouraging'

Badly in need of a win, BioMarin ($BMRN) released what it described as encouraging midstage data from a small study today showing its blood disorder gene therapy saw high factor VIII rates--but raised liver enzymes were noted.

In its Phase I/II study, BioMarin tested 8 patients with its experimental hemophilia A gene therapy BMN 270 with a severe form of the bleeding disease. Initial data released by the San Rafael, California-based biotech show that 2 high dose patients saw increasing levels of Factor VIII above 50%, while 5 out of 6 high dose patients show Factor VIII levels above 5%.

Patients with the condition are not able to produce enough functional Factor VIII to prevent bleeding--so raising their levels is necessary to help them manage.

The 8 patients with severe hemophilia A received a single dose of BMN 270, 6 of whom have been treated at the highest dose of 6 x 1013 vg/kg, and to date, post-treatment follow-up ranges from 5 to 16 weeks. 

At last observation, BioMarin said that patients at the highest dose experienced increasing Factor VIII activity levels ranging between 4% and 60%, with 5 of 6 patients treated at the high dose now over 5% and 2 of 6 at over 50%. All high dose patients improved from severe to moderate, mild or normal range in terms of factor levels, based on World Federation of Hemophilia criteria.

But BioMarin noted that while the efficacy appeared strong, there was a slight safety concern given that ALT liver enzyme levels increased across some patients--but a prophylactic corticosteroid therapy was given, whereby the levels have to date dropped back to normal, according to the company.

BMN 270 is one of a new set of investigational drugs designed to address the underlying genetic defect that prevents the expression of functional Factor VIII.

The drug does this by using an adeno-associated virus (AAV) vector to deliver a functional copy of the factor VIII gene to patients’ own cells, with the aim of a single infusion of BMN 270 providing a long-lasting increase in Factor VIII levels.

There are currently a number of drugs on the market for the hemophilia A and B, including Biogen’s ($BIIB) Factor IX Alprolix and long-acting factor VIII Eloctate, as well as meds from Baxalta ($BXLT), Novo Nordisk ($NVO), Bayer and CSL. Gene therapy is seen as the next gen treatment class for the condition. 

Mark Schoenebaum, an analyst at Evercore ISI, said that while the data presented today were small numbers and of relatively limited follow up (in the high dose especially): “The data were encouraging (though looks like significant variability from patient to patient) and suggest a path forward for BMN 270 in hemophilia A (and potentially for hemo A gene therapy in general), and sets a reasonably high bar for competition that will follow.”

Other companies looking into the gene therapy space for the condition include Massachusetts-based Alnylam ($ALNY), which is working on a cutting-edge gene therapy that could one day cure the disease altogether. Biogen has also recently paid out a small investment in its hemophilia platform by partnering with two Italian research institutions to develop its own gene therapies--although the biotech is rumored to be selling off its hemophilia assets.

Hank Fuchs, chief medical officer at BioMarin, said: “We are encouraged by this early data on BMN 270 and the trend we are seeing in increasing Factor VIII levels over time. BMN 270 could have the potential to reduce and possibly eliminate the need for infusions of Factor VIII.”

BMN 270 has already been given an orphan drug designation in Europe and from the FDA, and Phase III design preparation and high volume manufacturing plans “are underway,” according to the company.

This is a good result for BioMarin, and comes at a time when the company has taken a beating in the past few months--with the rare disease biotech disappointing some analysts with its recent readout on a study for a type of Batten disease.

And before this, the FDA rejected its Duchenne muscular dystrophy drug--a severe disappointment that left some observers wondering about the company's credibility on R&D. Last month, the company also flubbed a key secondary endpoint for cognitive improvements in its rare disease candidate pegvaliase. The drug was seen as a substitute for BioMarin's near-term DMD expectations, although it did hit its primary endpoint.