New Medicines

Haemophilia A


New molecular entity
Spark Therapeutics
Spark Therapeutics

Development and Regulatory status

Phase II Clinical Trials
Jul 21Also has orphan status in EU [9].
Dec 20Analysts predict launch in US and ex-US in 2023, with 35% and 50% chance of success, respectively [7].
Sep 18Has breakthrough therapy and orphan drug status in US [3].


Single-dose recombinant adeno-associated viral (rAAV) vector composed of a bio-engineered capsid with liver specific enhanced tropism and a codon-optimized expression cassette that encodes the SQ-FVIII variant of a B-domain-deleted (BDD) human F8 gene.
It affects 1:4,000 to 1:5,000 live male births worldwide [1].
Haemophilia A

Trial or other data

Jul 22PI observational study (NCT03432520) is continuing to enrol by invitation; timescales unchanged [12].
Apr 22PI/II study (NCT03003533) published in NEJM 2021; 385: 1961-73 [11].
Dec 21Collection of primary outcome data is due to complete in PI/II study (NCT03003533). No changes announced for timelines in PIII (NCT03432520) study [10].
Jul 21Spark announces updated results of the open-label PI/II trial (NCT03003533) in patients (n=18) showing that administration of dirloctocogene samoparvovec (SPK 8011) resulted in sustained factor VIII (FVIII) expression in 16 of 18 participants with up to 4 years of follow-up. In the 16 patients with sustained FVIII expression, there was a 91.2% reduction in annualised bleed rate (ABR) and 97% reduction in annualised FVIII infusion rate (AIR) after vector administration [9].
Mar 21Recruitment completes in PI/II study (NCT03003533). Updated data has been presented at ISTH 2020 [8].
Jul 20Interim data from the PI/II study is from 14 participants who received a single administration of SPK-8011, two at a dose of 5x1011 vg/kg, three at a dose of 1×1012 vg/kg and nine at a dose of 2×1012 vg/kg. As of the June 3, 2020 data cutoff, results from the five total participants in the 5x1011 vg/kg and 1×1012 dose cohorts and seven participants in the 2×1012 vg/kg dose cohort show an acceptable safety profile, 91% reduction in annualized bleed rate (ABR), 96% reduction in FVIII infusions and stable and durable factor FVIII expression after between two and 3.3 years of follow-up. As previously disclosed, two of nine participants in the 2×1012 dose cohort lost FVIII expression likely due to a capsid-based immune response. The seven other participants in the 2×1012 dose cohort and the five total participants in the 5×1011 vg/kg and 1×1012 vg/kg dose cohorts continue to show stable and durable factor FVIII expression. These data represent the longest stable expression of FVIII following investigational gene therapy and reinforce the ability of AAV gene therapy targeting hepatocytes to achieve stable and durable FVIII expression [7].
Jul 20Spark Therapeutics intends to initiate patient dosing in a PIII trial in 2021. The PIII run-in study is ongoing - this study will evaluate the long-term safety and efficacy of SPK-8011 in males with hemophilia A, who have received a single intravenous administration of SPK-8011 in any Spark-sponsored SPK-8011 study. It will follow patients until end of 2022 [6].
Jul 20Updated data for PI/II study (NCT03003533) has been presented at ISTH 2020. PI long-term follow-up study of 100 patients who have received SPK-8011 in any prior Spark-sponsored SPK-8011 study is ongoing [6].
Jun 19Spark Therapeutics initiated an observational phase I, six-month run-in study (NCT03432520) with an estimated primary completion date of December 2022 [5].
Dec 18Data on the first participants in the ongoing Phase 1/2 clinical trial in hemophilia A found that the 5x1011 vg/kg and 1x1012 vg/kg dose cohorts had dramatic reductions in bleeds and infusions as well as stable FVIII activity with up to 78 weeks of follow-up [4].
Dec 16PI/II trial evaluating safety and efficacy of SPK 8011 in male patients with haemophilia A starts (NCT03003533). The open label study plans to enrol 30 male patients in the US, Australia and Canada. Primary outcome measures are number of study-related adverse events, including clinically significant abnormal laboratory values & changes from baseline in FVIII activity levels after a single outpatient administration of SPK-8011 after 52 weeks. Collection of these data is due to complete Aug 19 [2].