Roche loses spark for gene therapy, axing hemophilia A candidate from pipeline

Roche’s gene therapy ambitions have taken another blow. Shortly after writing down (PDF) the value of one of Spark Therapeutics’ hemophilia A candidates, the Swiss drugmaker has removed a second therapy aimed at the disease from its midphase pipeline.

Buying Spark for $4.3 billion in 2019 gave Roche control of hemophilia A gene therapies that could have posed a threat to its existing drug Hemlibra. Revised sales forecasts forced Roche to take a charge of 519 million Swiss francs ($606 million) related to one of the hemophilia gene therapies, SPK-8011, in its most recent annual results, but the value of the second candidate remained unchanged at that time.

Now, Roche has removed (PDF) the second gene therapy candidate from its pipeline. Spark designed the other hemophilia A gene therapy, known as RG6358 or SPK-8016, for use in up to 30% of people with severe or moderately severe hemophilia A who have inhibitors to factor VIII (FVIII). 

The goal, as Spark co-founder Katherine High, M.D., told investors in 2018, “is to eradicate the inhibitor using a gene-based approach.” Spark shared preliminary data on four patients with no history of FVIII inhibitors in 2021 and kept going toward its targeted primary completion date, which slipped from April 2020 to March 2023 over the course of the study.

Dropping RG6358 at the phase 1/2 stage leaves Roche’s hemophilia A gene therapy ambitions resting on SPK-8011, also known as dirloctogene samoparvovec. Roche listed the start of a pivotal phase 3 of the candidate among the second quarter achievements of its hemophilia A franchise, which continues to grow in the absence of gene therapies because of rising demand for Hemlibra. 

On an earnings call with journalists this morning, Roche Pharmaceuticals CEO Teresa Graham explained that RG6358 had been removed from the pipeline because it “simply 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 hoped, the responsible thing is to refocus your resources on something that you believe will,” Graham said. 

“Developing in the gene therapy space is exceptionally difficult,” she added. “And I think we've seen that in the industry, there's a lot of difficulty in making sure that you've got the right vector that you're directing at the right target and that you're creating a treatment that is actually going to be maximally impactful and durable over time.”

Still, Graham explained that Roche has been “very pleased” with how Spark has integrated with its parent company and pointed to the pharma's continued efforts with SPK-8011.

Roche disclosed the removal of RG6358 from its midstage pipeline alongside details of changes in phase 1. One of the culled phase 1 candidates was reportedly the first T-cell receptor-like bispecific antibody to enter a clinical trial. Roche began a phase 1 trial of the candidate, RG6007, in 2020 to start exploring if targeting the HLA-A2-WT1 complex on tumor cells and CD3 on T-cells treats acute myeloid leukemia. The Swiss drugmaker “put a temporary hold on recruitment until further notice” in April.

RG6007 was followed out of the door by RG7637 and RG6392. Roche moved (PDF) RG7637 into phase 1 in 2020, listing it as a treatment for neurodevelopmental disorders. The candidate, now listed as being in development in psychiatric disorders, left the pipeline in the latest cull. RG6392, also called RO7497987, is a cancer candidate with a publicly unknown mechanism that Roche was testing in healthy volunteers.