It’s a measure of the anticipation about gene therapy that data positive data in three haemophilia patients caused UniQure shares to close up almost 36% yesterday, taking its market cap to almost $1.2bn.
The phase 2b results for UniQure’s AMT-061 candidate for haemophilia B keeps the Dutch-US biotech in contention with Pfizer and Spark, its main competitor in the development of a gene therapy for the bleeding disorder.
Both are delivering the gene for the missing clotting factor in haemophilia B (Factor IX) using adeno-associated virus (AAV) vectors, in the hope of allowing patients to produce their own factor IX and be freed from regularly injecting the recombinant protein.
UniQure’s new data shows that the three patients treated with therapy achieved Factor IX levels that were on average 31% of the normal level six weeks after administration, and seemed to be increasing thereafter, which is close the level achieved by Pfizer/Spark’s SPK-9001 (fidanacogene elaparvovec) in mid-stage testing.
That’s a big win, as it is estimated that a 12% level should do away with obvious bleeds while 20% should also tackle the symptomless, minor bleeds that can progressively cause health problems in haemophilia. UniQure had to abandon an earlier version of its therapy (AMT-060) after it became clear that it was not raising Factor IX levels as well as rival therapies, only managing around 7% of normal.
The new data also shows that over the first 24 weeks after treatment, none of the three patients needed infusions of recombinant Factor IX, had a bleed, or developed an immune reaction to the gene therapy that required immunosuppressive drugs. And the safety data also looks good so far, with one of the three having a mild elevation in liver enzymes that went away without treatment.
AMT-061 uses a new Factor IX variant – called the Padua construct – that is more potent at causing blood to clot and is also used in Pfizer/Spark’s candidate. Thankfully for UniQure, the FDA allowed it to swap to the new version without having to redo the groundwork on AMT-060, otherwise it would have slipped behind in the head-to-head race.
UniQure says it will file the new data with the FDA and EMA before the end of the year, and hopes to start dosing patients in a phase 3 trial of AMT-061, called HOPE-B, in the first quarter of 2019. It recently recruited the first patient for that study.
HOPE-B will recruit around 50 adults with moderately severe or severe haemophilia B who will receive a single dose of AMT-061 after a six-month lead-in period. The primary endpoint of the study will be the Factor IX activity level, while secondary endpoints will include annualised bleed rates, annualised replacement therapy use and safety.
UniQure’s Robert Gut
“We are highly encouraged by these early data, where all patients achieved therapeutic levels of FIX activity,” said Robert Gut, M.D., Ph.D., chief medical officer of uniQure. “Based on the long-term FIX data from our phase 1/2 trial of AMT-060, where we saw FIX activity levels continue to increase beyond the levels achieved at six to ten weeks, we are hopeful that we will continue to see similar trends in these patients.”
Another emerging competitor is UK start-up Freeline Therapeutics, which has just raised around $112m to help advance its haemophilia B gene therapy candidate which has also shown early promise in clinical trials.