Spark Therapeutics Provides Update on SPK-8011, Other Potential Gene Therapies for Hemophilia

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by Alice Melão |

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SPK-8011 may be a safe treatment strategy for patients with severe or moderately severe hemophilia A, achieving an overall 97% reduction in annual bleeds, according to preliminary data from an ongoing Phase 1/2 trial.

The trial (NCT03003533) is intended to explore the safety and efficacy of a single intravenous (into-the-vein) administration of SPK-8011 in about 30 patients with confirmed hemophilia A. To date, three different doses of the potential gene therapy have been tested in the first 12 participants.

During the follow-up period, the patients did not develop any antibodies that could inhibit SPK-8011 clotting activity. In general, the treatment was found to be safe and well-tolerated. Two patients experienced a clinically relevant increase in liver enzymes that was resolved with steroid treatment.

Researchers reported a 94% reduction in bleeds and a 95% decrease in additional clotting factor VIII (FVIII) infusions across all three treatment doses four weeks after SPK-8011 administration.

All five patients who were treated with the two lower doses of SPK-8011 experienced marked reductions in bleeds and infusions, and maintained stable FVIII activity after up to 78 weeks of follow-up. These patients are still undergoing further evaluations.

Of the seven patients who received the higher dose of SPK-8011, five showed stable FVIII levels four weeks after administration of the gene therapy. These patients did not have any bleeds during the 46 weeks of follow-up, and had more than a 99% reduction in FVIII infusions.

“These updated data continue to demonstrate impressive reductions in bleeds and infusions across all doses studied,” Katherine A. High, MD, president and head of research and development at Spark Therapeutics (the developer of SPK-8011), said in a press release.

During the trial, seven of the participants received a tapering course of oral steroids. This complementary treatment approach can prevent a rise in liver enzymes, but also has been shown to help prevent FVIII levels from dropping due to immune-mediated reactions.

These results show that SPK-8011 may be a safe strategy to induce sustainable FVIII levels, “resulting in an excellent preliminary efficacy profile with an overall 97% reduction in annualized bleeding rate (ABR) and annualized infusion rate (AIR),” according to the researchers.

These findings were discussed at the 60thAmerican Society of Hematology Annual Meeting in San Diego. The oral presentation was titled “A Phase 1/2 Trial of Investigational Spk-8011 in Hemophilia a Demonstrates Durable Expression and Prevention of Bleeds.”

Spark Therapeutics expects to announce additional data from this Phase 1/2 trial in hemophilia A patients in mid-2019. This is anticipated to include data from a new group of patients who will receive SPK-8011 plus prophylactic (preventive) steroids to prevent unwanted immune reactions.

Recently, the company began an observational study (NCT03432520) that will follow patients who participated in the Phase 1/2 trial of SPK-8011 for an extended period of time. During this study, researchers will explore the long-term safety and efficacy of SPK-8011.

“Throughout this progress, we have built unique competencies in the discovery, development and delivery of genetic medicines that guide our portfolio strategy — from how we discover and develop gene therapies, to how we select targets and prioritize our programs, to how we manufacture and commercialize these novel therapies globally,” Jeffrey D. Marrazzo, CEO of Spark Therapeutics, said in another press release.

“We believe these competencies increase our ability to successfully break barriers by transforming the research in our labs into life-altering gene therapy products for patients and position us well for continued growth and success,” he said.

Spark Therapeutics is also developing a new potential gene therapy, SPK-8016, specifically for the treatment of patients with hemophilia A, or factor VIII deficiency, who have developed inhibitors on currently available therapies.

To test the activity of SPK-8016, the company has launched a Phase 1/2 trial (NCT03734588), which is expected to enroll about 30 patients who will be assigned to receive a single administration of increasing doses of the investigational therapy.

In the first part of the study, researchers will assess the safety and tolerability of SPK-8016, and will define the optimal dose for further testing. In the second part, the efficacy of the selected dose will be assessed.

More recently, Spark Therapeutics announced that it has completed the transition of SPK-9001 for hemophilia B to Pfizer, following the terms of their collaborative agreement. Pfizer will now be responsible for the further development of this gene therapy.

Clinical data has demonstrated that SPK-9001 could effectively treat bleeding for hemophilia B patients, showing a 98% reduction in annualized bleeding rates.

Pfizer has begun an observational study (NCT03307980) that will follow patients who participated in the Phase 2 trial of SPK-9001 (NCT02484092) for an extended period of time.