Roche mothballs another hemophilia A gene therapy under Spark amid plans to debut new hematologic asset

Following the apparent elimination of a late-stage gene therapy study last week, Swiss drug juggernaut Roche has confirmed that it’s axing a hemophilia candidate inherited in its 2019 buyout of Spark Therapeutics.

In an emailed statement, a Roche spokesperson told Fierce Biotech that the company is discontinuing further development of Spark’s experimental hemophilia A gene therapy dirloctocogene samoparvovec, also known as SPK-8011.

The move comes after the entry for the candidate’s phase 3 study was listed as “withdrawn” last week on the U.S.’ online clinical trial repository. The entry on ClinicalTrials.gov attributes the withdrawal to a "strategic decision" by Roche. 

The terminated study, dubbed KEYSTONE 1, was launched in March but never actually enrolled any patients, according to ClinicalTrials.gov.

Roche’s spokesperson confirmed the termination of the study and explained that the company is mothballing SPK-8011 as it introduces a new, enhanced function factor VIII (FVIII) hemophilia A candidate to its gene therapy pipeline.

“This decision is based on our belief that an enhanced function FVIII variant has the potential to address remaining unmet needs and reduce the treatment burden for patients,” the spokesperson explained. “This decision builds on the promising results seen in the phase 1/2 dirloctocogene samoparvovec study, which assessed the safety and efficacy of the factor VIII gene transfer treatment in individuals with hemophilia A, demonstrating favorable safety, durability and predictability using a low-dose approach.”

The pharma has not yet incorporated this new program into its online pipeline, which was last updated Oct. 23 and still lists SPK-8011.

Roche first got its hands on SPK-8011 and Spark itself when it purchased the Philadelphia gene therapy specialist for $4.3 billion in 2019. That said, the Roche unit’s gene therapy ambitions have run into turbulence on multiple occasions since then.

Last year, Roche had to write down (PDF) the value of the now-terminated SPK-8011, incurring a charge of 519 million Swiss francs ($606 million at the time) over revised sales forecasts around the personalized medicine candidate.

Shortly thereafter, the pharma removed a different hemophilia A gene therapy, known as RG6358 or SPK-8016, from its pipeline. The axed candidate had been in early clinical-stage development for use in up to 30% of people with severe or moderately severe hemophilia A who have inhibitors to FVIII.

More recently, Roche punted Spark’s Pompe disease gene therapy candidate SPK-3006 from its pipeline this July, which the company credited to a “strategic portfolio prioritization within Spark.”

At the time, a Roche spokesperson added that Pompe disease already boasts an established standard of care and multiple different companies are pushing potential gene therapy solutions through the clinic.

Elsewhere on the personalized medicine front, Roche in October inked a new deal with Dyno Therapeutics that could be worth more than $1 billion. Under the pact, Dyno—with whom Roche struck a separate gene therapy accord in 2020—is on deck to design novel adeno-associated virus vectors with “improved functional properties” as delivery tools for gene therapies.

Roche hopes to use Dyno’s technologies, which leverage artificial intelligence and high-throughput in vivo data, to target neurological diseases.