‘Cure for hemophilia within reach’ as BioMarin and Spark gene therapies shine

While clinicians attending the American Society of Hematology meeting in Atlanta this weekend were anticipating a flurry of exciting data, the conference wasn’t entirely prepared for the actual blizzard which struck huge swathes of the Deep South.

However despite some severe travel disruptions, the weather couldn’t freeze out the conference, which saw huge crowds of people attending sessions where some exceptional data was presented.

The first big buzz of the congress came from BioMarin’s gene therapy for haemophilia, valoctocogene roxaparvovec (formerly BMN 270).

BioMarin’s treatment looks to be truly groundbreaking, as the latest data shows 11 out of 13 patients who received a single infusion of the gene therapy showing their Factor VIII were at ‘normal or near-normal levels’ 19 months after treatment. This was in addition to earlier data which saw 10 of the patients experiencing a complete absence of the bleeds which characterise the disease.

This prompted the independent editorial in the New England Journal of Medicine to declare “A Cure for Hemophilia within Reach,” which also noted the promising safety profile of the reatment.

The therapy uses a viral vector to transfer a functional copy of the gene responsible for producing Factor VIII, which is mutated in people with haemophilia A, into the patient's body.

The company is in a pitched battle with Spark Therapeutics to be the first to develop a gene therapy for the haemophilia A, and BioMarin got its hugely impressive phase 1/2 data out on Saturday, with Spark having to wait until later today.

Just a few days ago Spark (with its partner Pfizer) released its own hugely impressive results from its haemophilia B gene therapy.  This is set to transformative for these patients, however haemophilia A is not only considered the more challenging genetic mutation to fix, it is also six times more prevalent, making it the more lucrative market

“The clinical data to date for this investigational gene therapy exceeded our expectations, in terms of increasing factor VIII levels and reducing the annualised bleed rate,” said lead researcher Dr John Pasi, professor of haemostasis and thrombosis at Barts and the London School of Medicine and Dentistry and haemophilia clinical director at Barts Health NHS Trust.

“Many clinical trial participants have seen factor VIII levels at or close to normal. This clinical result has the potential to improve the lives of patients who now must infuse themselves with factor VIII as often as every other day. With this experimental treatment, we are researching whether it may be possible for haemophilia A patients to reduce or eliminate factor VIII treatment over an extended timeline.”

Dr Pasi will present the data at the congress at 7:00 a.m. EST today , with the lead investigator on Spark’s haemophilia B and haemophilia A studies, Lindsey A. George, M.D., attending physician in the Division of Hematology at Children’s Hospital of Philadelphia, presenting at the same time.

The gene therapies aren’t the only promising new treatments in haemophilia A – Roche has just had its new biologic treatment Hemlibra (emicizumab) approved in the US. It helps patients who have developed ‘inhibitors’, which mean they no longer respond adequately to infusions of Factor VIII. This gives it something to offer over and above the as-yet-unapproved gene therapies.

These have steered clear of these harder-to-treat patients so far, however they will be the next group BioMarin and Spark will address.

Roche have been able to price Hemlibra at $482,000, as the cost of treating patients with inhibitors is already close to this figure.

The gene therapies, once approved, are anticipated to be priced at well over $500,000 – although quite how far over is yet to be seen, as outrage at high drug costs has tempered pharma pricing in recent months.

Both BioMarin and Spark will have to launch pivotal trials for their respective products in 2018, with filing likely in 2019. In terms of figuring out a pricing model with US payers goes, Spark will have the lead, as its treatment for a rare blindness is expected to gain approval within weeks, which will make it the first ever gene therapy approved in the US.

More to follow from ASH17: The haemophilia breakthroughs aren't the only major studies unveiled. The CAR-T field's onward push into haemato-oncology is grabbing headlines, with early stage data from Celgene and bluebird's BCMA-targeting CAR-T in multiple myeloma being a stand-out trial in this field.