Potential hemophilia A gene therapy SPK-8011 moves to Phase 3

Meanwhile, Roche discontinues another experimental therapy, SPK-8016

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Roche is initiating a Phase 3 clinical trial to test the experimental gene therapy SPK-8011 in people with hemophilia A.

The company announced the move in its 2023 half-year results. At the same time, however, Roche is discontinuing the development of another investigational hemophilia A gene therapy called SPK-8016.

Hemophilia A is caused by mutations that interfere with the production or function of a clotting protein called factor VIII (FVIII). Both SPK-8011 and SPK-8016 aim to deliver a healthy version of the gene encoding this protein to patient cells, thereby restoring their ability to produce functional FVIII.

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These two gene therapies were developed originally by Spark Therapeutics, which was acquired by Roche in 2019.

SPK-8011, also known as dirloctogene samoparvovec, has been tested previously in an open-label Phase 1/2 trial (NCT03003533), which sought to assess the safety and efficacy of one-time dosing with the therapy in about 50 people with hemophilia A.

Data from that study and its long-term extension study (NCT03432520) showed the therapy increased FVIII activity in 21 of 23 patients with available data. The two exceptions were patients who had experienced an immune reaction against the viral vector that the therapy uses to deliver its genetic payload. In the 21 patients who experienced an increase in FVIII activity, average bleeding rates decreased by more than 90% after up to five years of follow-up.

Phase 3 study could be pivotal

SPK-8011 is now moving into Phase 3 testing, according to Roche. The company did not provide details on the trial’s design or timing, but said the study is expected to be pivotal — meaning that, if results are positive, the trial may serve as the basis for applications seeking approval of SPK-8011.

SPK-8016, also known as RG6358, is a gene therapy specifically designed for the treatment of hemophilia A patients who have developed FVIII inhibitors — neutralizing antibodies that bind to FVIII replacement therapies and lower their effectiveness. The therapy was used to treat four patients in a Phase 1/2 study (NCT03734588), with preliminary results suggesting it could reduce bleeding rates and increase FVIII activity.

Roche did not specify the reason for discontinuing the development of SPK-8016, disclosing only that the therapy no longer will be pursued in Phase 2 development.

The company did report continued increases in the use of Hemlibra (emicizumab-KXWH), an under-the-skin injection therapy sold by Roche that’s approved to treat hemophilia A patients with or without FVIII inhibitors. So far, about 21,000 people around the world have been treated with Hemlibra, according to Roche.