Spark Therapeutics, Inc. announced updated multi-year results from its Phase 1/2 clinical trial of investigational SPK-8011 for patients with hemophilia A. With up to five years of follow-up, the data showed that a single infusion resulted in sustained factor VIII (FVIII) expression and clinically meaningful reductions in annualized bleed rate (ABR) and annualized FVIII infusion rates (AIRs). These data were presented at the 64thAmerican Society of Hematology (ASH) annual meeting As of the data cutoff (Oct. 4, 2022), 21 of 23 (91%) participants across all dose cohorts experienced sustained expression of FVIII with up to five years of follow-up, including two participants who completed five years of follow-up.

Of these 21 participants, the data showed a 92% (95% CI: 78-97%) reduction in ABR for all bleeds, with all-bleed ABR of 0.98 (95% CI: 0.46-2.08) post-infusion compared to 11.62 (95% CI: 7.42-18.19) pre-infusion. 16/21 (76%) participants had an ABR of <1 for treated bleeds and 19/21 (90%) had an ABR of <1 for spontaneous treated bleeds following investigational SPK-8011 infusion. Additionally, the data showed a significant reduction in FVIII concentrate consumption, with AIRs of 0.3 (0.0, 1.4) post-infusion compared to 85.5 (40.0, 104.0) pre-infusion.

In the updated safety analysis, there were no new safety signals reported related to investigational SPK-8011; no deaths, no thrombotic events, and no FVIII inhibitor development were reported. 11 participants experienced transient non-sustained asymptomatic ALT elevations during the expected window of presumed capsid immune response; all were mild except one participant who experienced a Grade 3 ALT elevation that was transient and asymptomatic. As previously disclosed, another participant experienced Grade 2 alanine transferase elevation, which qualified as a serious adverse event (SAE) and subsequently resolved, resulting in the only SAE related to investigational SPK-8011 to date.

All ALT elevations were resolved with the use of immunomodulation agents. Two patients from the high dose cohort lost FVIII expression due to a presumed capsid immune response, as previously disclosed. Investigational SPK-8011, a novel bio-engineered adeno-associated viral (AAV) vector utilizing the AAV-LK03 capsid, also referred to as Spark200, contains a codon-optimized human factor VIII gene under the control of a liver-specific promoter.

The Food and Drug Administration (FDA) granted orphan-disease designation and breakthrough therapy designation in the U.S., while the European Commission has granted orphan designation to SPK-8011. Interim results from the phase 1/2 study were published online in the New England Journal of Medicine (NEJM) in November 2021. The Phase 1/2 study, titled “A Gene Transfer Study of SPK-8011 for Hemophilia A,” is being conducted by Spark Therapeutics, Inc. to determine the safety and efficacy of the factor VIII gene transfer treatment with SPK-8011 in individuals with hemophilia A. (Trial identifier NCT03003533).