This afternoon, shares of Spark Therapeutics (ONCE 46.37, -27.01) trade about 36.9% lower in reaction to the company’s Hemophilia A and B data announced at American Society of Hematology (ASH) Annual Meeting and Exposition over the weekend.
The catalyst behind today’s weakness is the disappointing Hemophilia A data. The crux of the criticism stems from the data comparison of ONCE’s SPK-8011 hemophilia A treatment to peer BioMarin Pharm (BMRN 87.66, +5.67 +6.9%) valoctocogene roxaparvovec’s. Namely, ONCE’s SPK-8011 lagged BMRN’s treatment’s annualized infusion rate (AIR): this morning ONCE’s SPK-8011 reported an AIR reduction of 98% to a mean of 1.2, compared to BMRN’s valoctocogene roxaparvovec which reported an AIR reduction to zero in six patients. The data for both the hemophilia A and B treatments from ONCE are described below:
SPK-8011 Phase 1/2 --
- Specifically, ONCE announced dosage of seven participants in the Phase 1/2 clinical trial of SPK-8011 in hemophilia A. The first four participants, who have been followed at least 12 weeks post infusion, have reduced their overall annualized bleeding rate (ABR), calculated based on data after week four, by 100% (calculated based on data after week four; 82% based on data after infusion) to a mean of 0 (1) annualized bleeds as of the data cutoff, compared to a mean of 5.5 annualized bleeds before a single administration of SPK-8011.
- Similarly, their overall AIR was reduced about 98 percent (calculated based on data after week four; 96 percent based on data after infusion) to a mean of 1.2 (2.5) annualized infusions as of the data cutoff, compared to a mean of 57.8 annualized infusions before SPK-8011 administration. No serious adverse events have been observed to date.
- As of the Dec. 6, 2017, data cutoff, two participants have received a single administration of SPK-8011 at an initial dose of 5 x 1011 vector genomes (vg)/kg body weight and have now been followed for more than 40 weeks and 30 weeks. During this time, participant one has achieved sustained expression with a mean factor VIII activity level after week 12 of 10% (range as of the data cutoff: 7 -11%). Participant two has shown different kinetics of factor VIII expression. His factor VIII level, as of the data cutoff, is 37%, and the mean factor VIII level since week 12 is 16% (6-37%).
- Two additional participants, infused at a dose of 1 x 1012 vector genomes (vg)/kg body weight, have also achieved therapeutic levels of factor VIII. They have now been followed for 19 weeks and 14 weeks and have mean sustained factor VIII activity levels of 9% (7-12%) and 13% (7-24%) of normal, respectively, as of the data cutoff. Both participants have completed a precautionary tapering course of corticosteroids.
- Three more participants have been infused, one at the 1 x 1012 vector genomes (vg)/kg body weight dose and two at a dose of 2 x1012 vector genomes (vg)/kg body weight. Results for these three participants are too early to report as of the data cutoff.
- In this study, none of the seven infused participants has reported a serious adverse event, including no factor VIII inhibitors, no thrombotic events and no factor VIII activity levels that may increase risk of thrombosis.
SPK-9001 Phase 1/2 --
- ONCE and Pfizer (PFE 36.02, +0.28 +0.8%) announced that, with a cumulative follow-up of more than 13 patient years of observation, all 11 participants in the ongoing Phase 1/2 clinical trial of investigational SPK-9001 for the treatment of patients with hemophilia B had discontinued routine infusions of factor IX concentrates and shown sustained steady-state factor IX activity levels with no serious adverse events, thrombotic events or factor IX inhibitors observed.
- Based on individual participant history for the year prior to the study, the overall annualized bleeding rate (ABR) was reduced by 97% (calculated based on data after week four; 95% based on data after infusion) to a mean of 0.3 (0.5) annual bleeds, compared to a mean of 10.5 bleeds annually before SPK-9001 administration.
- Overall annualized infusion rate (AIR) was reduced 99% (calculated based on data after week four; 97% based on data after infusion) to a mean of 0.8 (1.7) annual infusions, compared to a mean of 62.5 infusions per year before SPK-9001 administration.
- As of the Nov. 29, 2017 data cutoff, the mean steady-state factor IX activity level at 12 weeks post-administration for the 11 participants was 36% of normal (range as of the data cutoff: 15-78%). As of the data cutoff, the last participant to be infused, who received SPK-9001 manufactured using an enhanced process, was out eight months following SPK-9001 infusion, with a mean factor IX activity level of 60%.
- The company will enroll up to four additional participants in the current Phase 1/2 clinical trial who will receive SPK-9001 manufactured using an enhanced process to test its comparability to the SPK-9001 received by the first 10 participants enrolled in the ongoing trial.
A teleconference detailing the results will begin today at 12:30 p.m. ET.