JP Morgan 2017: BioMarin solidifies status as lead dog in haemophilia A gene therapy

The viability of BMN 270 was in serious doubt after liver enzyme elevations caused BioMarin to suspend a Phase I/II trial last June, but updated results presented at this week’s JP Morgan Healthcare Conference suggest the future has never looked brighter for the gene therapy to treat haemophilia A.

It may be a little premature for the likes of Shire and Roche to panic about gene therapy’s disruptive potential in haemophilia A, but the latest update for BioMarin’s BMN 270 will no doubt capture the attention of some of the more established players.

On January 9, BioMarin reported that six of seven patients who received the highest dose of a single infusion of BMN 270 have achieved and maintained therapeutic levels of Factor VIII after between 34 and 50 weeks, while the number of bleeding events and prophylactic infusions of Factor VIII replacement therapies have both decreased by more than 90 percent.

What’s more, there have been no significant changes in liver enzyme levels observed since the last clinical update in July despite the fact that all seven patients in the high-dose group have been weaned off steroids. One patient’s enzyme levels did remain slightly above normal, albeit only 5 percent above the threshold. This will come as an especially big relief for many investors after serious doubts were raised about BMN 270’s safety profile last summer, at which point enzyme levels were elevated in all patients leading to the temporary study suspension.

"BMN 270 continues to demonstrate the ability to produce high and sustained levels of Factor VIII, with an acceptable safety profile," noted Cowen analyst Phil Nadeau. "Levels of Factor VIII expression above 12 percent of normal have been shown to change the natural history of haemophilia and result in the virtual elimination of spontaneous bleeds," suggesting that even the lone patient whose expression levels remain below 50 percent (observed as being 16 percent as of last month’s data cut off) is likely to be experiencing a clinical benefit from BMN 270 therapy.

Thus, BioMarin seems to have provided some evidence to rebut the two main questions hanging over BMN 270’s head, namely whether its durability of effect is robust and if liver enzyme levels (a marker of potential liver injury) would return to and remain normal.

One lingering question mark is the variability of BMN 270, with Factor VIII expression levels ranging up to 222 percent of normal in one patient, though importantly the activity levels appear to have stabilised from the July readout. A continued upward trend in patients already having supra-normal expression would no doubt have been a bigger concern.

The encouraging results mean that BioMarin’s guidance for beginning a pivotal Phase IIb trial of BMN 270 in 3Q17, pending the completion of a manufacturing facility, looks to be well within reach, and suggests the company is still at least a year ahead of competing haemophilia A gene therapy programmes.

See also: KOL Views: Gene therapies for haemophilia finally coming of age but risks – clinical and commercial – remain, according to leading expert

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