There are a slew of gene therapy companies trying to develop a long-lasting, perhaps even permanent treatment for hemophilia. The proof that these companies can really make an impact on the disease will come out in dribs and drabs from clinical trials over the next several years, and today, one of them, Dutch firm UniQure, did so with some promising early results.
UniQure (NASDAQ: QURE) this morning presented results from an early study of AMT-060, a gene therapy it’s developing for patients with hemophilia B. To be clear, these are numbers from just the first handful of patients in UniQure’s study, treated with a low dose of the gene therapy. And they’re early—the patient treated the longest is now 20 weeks post-treatment. For gene therapy to become a viable option for hemophilia, the effects will have to hold up for a long period of time, stop the dangerous, spontaneous bleeds that patients can suffer, and eliminate the need for frequent infusions of the recombinant factors that patients have to take to clot their blood.
But the early results are the kind that can make a meaningful impact if they continue to hold up. The first two hemophilia patients treated with AMT-060, about 12 and 20 weeks after treatment, are now producing 4.5 percent and 5.5 percent, respectively, of normal Factor IX. To put that in context, these patients have severe or moderately severe hemophilia, meaning they typically produce less than 1 to 2 percent of these levels, and rely on frequent infusions to get those numbers up.
Shares of UniQure jumped about 12 percent in pre-market trading on Thursday.
Bumping those Factor IX figures up by a few percentage points might not seem like a big deal, but getting a patient to produce even 5 to 10 percent of their normal levels of clotting factor can turn a severe case of hemophilia into a mild one, or significantly lower the risk of a spontaneous bleed. As ex-UniQure CEO Jorn Aldag told Xconomy last year: “We believe that if you exceed 5 percent, you have a drug.” (Aldag stepped down in December, leading many to speculate UniQure was preparing to deliver bad news on AMT-060).
Indeed, the study most point to as proof of gene therapy’s potential in hemophilia, run by academic groups at St. Jude Children’s Research Hospital and University College London, helped a small number of patients significantly reduce bleeding events. To that end, UniQure said that four of the five patients treated with a low dose of AMT-060 to date have stopped taking recombinant factor IX.
“Thus far, the overall tolerability and Factor IX expression profile in the low-dose cohort is encouraging for patients with hemophilia B and support the continuation of the study,” said study investigator Frank Leebeek, of the Erasmus Medical Center in Rotterdam, in a statement.
There are caveats here, of course. As has been seen with Bluebird Bio (NASDAQ: BLUE) over the past year, more patients with different characteristics can lead to variable results. Some patients given Bluebird’s gene therapy for beta-thalassemia have responded better than others. Similarly, it’s unclear who will and won’t respond to AMT-060 in the future, and how long those effects will last. UniQure also said that the first patient given the gene therapy had a “mild, transient” spike in liver enzymes around 10 weeks after treatment. This was alleviated after an 8-week course of the steroid prednisolone—a tactic the St. Jude’s/UCL group used in its study, the same way Spark Therapeutics (NASDAQ: ONCE) scientific founder Katherine High did more than 10 years ago when she saw a patient’s liver enzymes spike in a gene therapy study in hemophilia—but it’s worth watching as more patients take AMT-060.
UniQure is one of at least seven different groups developing gene therapy treatments for hemophilia. The others are Baxalta (NYSE: BXLT), Dimension Therapeutics (NASDAQ: DMTX), Spark, BioMarin Pharmaceutical (NASDAQ: BMRN), Sangamo Biosciences (NASDAQ: SGMO), and Biogen (NASDAQ: BIIB). Of the group, only Baxalta has produced early clinical trial results as of yet.
The difference between all of these players is technical, dealing with the types of viral “vectors,” or delivery mechanisms they’re using, as well as the actual genes being delivered into patients. They’re essentially different strategies to bump up levels of clotting factor, or steer clear of potential alarm bells from the immune system (for more on those differences, check out this piece on gene therapy in hemophilia). UniQure, for instance, is the only one in the group using an adeno-associated virus vector known as AAV5, which it licensed from the National Institutes of Health in 2011, and is using the same therapeutic gene as the St. Jude’s/UCL group.
The next update from UniQure’s trial will come at a scientific meeting during the second quarter. The company is holding a conference call this morning to discuss today’s results.