Spark slides on hemophilia A data, aims for phase 3

red blood cells
Spark plans to start phase 3 trials of the highest dose of its hemophilia A gene therapy later this year. (Arek Socha)

Spark Therapeutics’ hemophilia A gene therapy reduced bleeding by 97% in a phase 1/2 trial, building on data reported in December that suggested it may not be as potent as a rival in development at BioMarin.

The study tested three different doses of the treatment, SPK-8011, which is designed to remedy hemophilia A patients’ deficiency of clotting factor VIII. Two patients received a dose of 5 x 1011 vector genomes (vg)/kg body weight, three received 1 x 1012 vg/kg and seven received 2 x 1012 vg/kg. Four weeks after treatment, all three groups had twin 97% decreases in annualized bleeding rate and in annualized infusion rate.

Five of the seven patients on the highest dose had 100% reductions in bleeding rate and infusion rate. The treatment also boosted their factor VIII levels, on average, to 30% of normal. The Philadelphia-based biotech will move this dose into phase 3, starting with a run-in study slated to begin in the fourth quarter, Spark said in a statement.

Virtual Roundtable

ESMO Post Show: Highlights From the Virtual Conference

Cancer experts and pharma execs will break down the headline-making data from ESMO, sharing their insights and analysis around the conference’s most closely watched studies. This discussion will examine how groundbreaking research unveiled over the weekend will change clinical practice and prime drugs for key new indications, and panelists will fill you in on the need-to-know takeaways from oncology’s hottest fields.

But the data aren’t perfect; the treatment triggered an immune response in the remaining two patients that dropped their factor VIII levels to less than 5% of normal. One of the patients didn’t respond to oral steroids and had to be hospitalized. Spark was down about 30% before the market opened Tuesday.

RELATED: Spark’s hemophilia A data causes investor jitters

To avoid this kind of immune response in the future, Spark will add prophylactic oral steroids to its treatment, said Spark President and R&D chief Katherine High, M.D.

“These early data further support the dramatic impact on patient outcomes that can result from factor activity levels above 12% and bring us closer to our goal of one day eliminating spontaneous bleeding altogether, while potentially freeing patients with hemophilia A from the need for regular infusions,” High said.

RELATED: A transplant of CRISPR-edited liver cells could replace lifelong injections for hemophilia B patients

People with hemophilia A need lifelong treatment, which includes regular infusions of factor VIII or a clotting promoter that raises their factor VIII levels. Treatments can be expensive and time-consuming, and because they require an injection, patient adherence can become an issue. A gene therapy would be a game changer in the space.

Spark is playing catch-up to BioMarin, whose own hemophilia A gene therapy is in phase 3. At two years after infusion with BioMarin’s Valoctocogene Roxaparvovec, patients’ average factor VIII levels were at 59%, outperforming Spark’s SPK-8011. However, the average factor VIII levels at one year postinfusion were close to double that, at 104% of normal, suggesting that the treatment’s efficacy wanes over time.

Suggested Articles

Novartis is forging ahead with the development of spartalizumab in "many, many other indications" despite the setback.

Chi-Med has detailed plans to seek approval from the FDA later this year in part on the strength of data from Chinese phase 3 trial.

Takeda tapped Roche’s Foundation Medicine to develop tissue- and blood-based companion diagnostic tests for its portfolio of lung cancer therapies.