Roche moves one Spark hemophilia gene therapy into PhIII, cuts another 

As Roche finally puts one gene therapy for hemophilia A into Phase III, it’s discarding another.

Roche disclosed the removal of RG6358, or SPK-8016, in its second quarter earnings presentation, where it also noted that a Phase III trial of RG6357, or SPK-8011, has been initiated. The company is aiming to open enrollment for the study, which will be called Keystone1, later this year, a spokesperson confirmed in an email.

Both programs are under Spark Therapeutics, a subsidiary of Roche, following a $4.8 billion buyout in 2019. At that time, Spark had already started Phase I/II studies for the two programs, with an eye toward a pivotal SPK-8011 trial within a couple of years. But Roche ultimately delayed the trial initiation to optimize the dose and treatment regimen.

Teresa Graham

The forthcoming Keystone1 SPK-8011 trial will capture data from a 66-week period and then track patients for 10 years to collect long-term safety and efficacy data, the Roche spokesperson told Endpoints News.

When asked about the SPK-8016 cut on a media call, Roche Pharma CEO Teresa Graham said the gene therapy “wasn’t having the impact that we thought that it was going to have.”

“When you know that your treatment isn’t going to be able to impact patients the way that you hope, the responsible thing is to refocus your resources in something that you believe will,” she said.

Roche CEO Thomas Schinecker added that Roche is looking for “durable, long-lasting effects.” With gene therapies, “you basically have one shot” before patients develop antibodies against the vector used to deliver the therapy, he explained.

Thomas Schinecker

While Spark was once among the frontrunners to bring a hemophilia A gene therapy to the market, it will now be playing distant runner-up to BioMarin, which landed FDA approval for Roctavian in June after multiple delays and a challenging rollout in Europe. The FDA had initially rejected the therapy and demanded more durability data.

SPK-8011, also dubbed dirloctocogene samoparvovec, consists of a bioengineered AAV vector made with the AAV-LK03 capsid, a human factor VIII gene and a liver-specific promoter, according to Roche.

At the ASH conference in December, Roche presented new data showing that 21 of 23 patients who received SPK-8011 saw sustained expression of factor VIII after up to five years of follow-up. Among the 21 patients, the annualized bleed rate was reduced by 92%, with a corresponding drop in use of factor VIII replacement.

In its Q2 presentation, Roche noted that it’s also scrapped four Phase I programs. In addition to a SQZ-partnered cancer vaccine that it decided not to take an option on after reviewing the data package, it also axed RG6007, a T cell receptor-like T cell engager tested for acute myeloid leukemia, because “clinical activity seen so far is below our target.” The last two, RG7637 for psychiatric disorders and RG6392 for oncology were dropped for “strategic” reasons.

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