Looking for leg up in hemophilia B gene therapy race, uniQure flashes data that helped lead to $2B CSL deal
In the two-headed race to develop the first gene therapy for hemophilia B, uniQure just got a major leg up.
In a late-breaking abstract at ASH, the company released data from their pivotal 54-person Phase III trial, showing that it increased levels of Factor IX from below 2% of normal to 37% of normal after 26 weeks. Although the company will still need to collect 52-week data, the levels come in above what Pfizer has shown in early studies for their rival gene therapy and at or above what analysts suggested would be needed to show efficacy.
In an interview, CEO Matt Kapusta declined to disclose what number they had told the FDA they were going for, but said they viewed the result as an unmitigated success.
“I think [it] represents functionally curative levels for these patients,” Kapusta told Endpoints News. “So it’s very exciting.”
UniQure’s stock $QURE was up 6% on the news, from $42.76 to $45.50.
The secondary endpoints also proved positive but not perfect: 72% of patients recording no bleeding incidents after administration, while average usage of standard Factor IX replacement therapy fell by 96%.
The data provided public validation for CSL Behring and their surprise decision earlier this year to purchase the gene therapy in a milestone-heavy deal up to $2 billion. UniQure said at the time that CSL had already seen private interim data prior to purchasing the therapy. Kapusta said CSL saw 12-week data.
Analysts argued prior to the readout that any increase to at least 10% of normal should yield clinical effects. Stifel’s Melissa Scott argued “anything above 20%” would be effective. SVB Leerink’s Joseph Schwartz set the target range between 30 to 50%.
Stifels’ Paul Matties praised the Phase III data as “encouraging, though not surprising.”
Pfizer’s gene therapy, originally developed with Spark Therapeutics and now in its own Phase III, showed Factor IX rates at 23% after one year in a 15-person trial. Although the Big Pharma started dosing first, analysts expected uniQure to move faster.
Side effects were minimal. The most common events included heightened liver enzymes, infusion related reactions, headache, and flu-like symptoms. Between 13% and 15% of patients experienced each.
The company also noted that patients who had pre-existing antibodies to adenovirus performed no worse on the gene therapy, which is delivered through an adeno-associated viral vector.
The big question will now be how much data the FDA would require for approval. uniQure had originally appeared likely to file a BLA in 2021, but the entire hemophilia gene therapy was upended earlier this August after the agency handed BioMarin a CRL on their hemophilia A gene therapy, demanding more data on durability.
Kapusta said BioMarin’s problems were unique to BioMarin, pointing to data suggesting their gene therapy’s effects waned over time and the fact that the biotech chose to go for approval on just 26-week data from a subset of patients in their pivotal trial.
Still, he acknowledged that the feedback they received has shifted in recent months, with implications for their lead therapy. The agency “recently” asked uniQure to make bleeding incidents a co-primary endpoint of the trial, Kaputo said, alongside Factor IX levels.
That requirement, he argued, will alleviate concerns about their patient’s Factor IX levels, as it shows the therapy’s real world impact. The company will have to show non-inferiority on bleeding to the Factor IX replacement therapy that patients took prior to receiving the gene therapy.
“I think the data speaks for itself,” he said. ” The gold standard is bleeding.”
Kapusta said they will meet with the FDA to discuss a BLA after conducting their last 52-week follow-up on their last patient next March.
“And that provides data to support a traditional approval in hemophilia treatment,” he said.