Spark/Pfizer

Spark/Pfizer’s updated interim analysis of the Phase I/II trial of SPK-8011 in haemophilia A (as of January 2020) was presented at the ISTH virtual 2020 Congress [1].

5 men aged 34 – 52 had received SPK-8011 at a dose of 0.5 or 1×10¹² vg/kg. Results are reported for 106 – 142 weeks post-dose
Steady state factor expression was achieved after 8 – 12 weeks
In two patients who received the lower dose, factor VIII activity was 6.9% and 8.4%
In three patients who received the higher dose, factor VIII activity was 5.2% – 20%; two of these patients required steroids for 7 weeks
Over >2-years’ follow up, annualised infusion rate was reduced by 95%
Annual bleeding rates were 0.4, 0.0, 0.4, 3.6 and 0.5, a reduction of 91%

In 2019, Pfizer began recruitment for BENEGENE 2, a Phase III trial of fidanacogene elaparvovec in 55 men with moderate to severe haemophilia B.

Pfizer is also running the Alta trial of giroctocogene fitelparvovec (formerly known as SB-525, developed by Sangamo) in men with severe haemophilia A. It is assessing four doses: 9×10¹¹ vg/kg, 2×10¹² vg/kg, 1×10¹³ vg/kg, and 3×10¹³ vg/kg. Patients’ mean age is 30 (range 18 – 47). Interim findings presented at the World Federation of Hemophilia 2020 Virtual Summit showed that:

In one patient with 61 weeks’ follow up who received 3×10¹³ vg/kg, factor VIII activity is 64%
Four patients required steroid therapy to treat elevated alanine aminotransferase

A Phase III trial (AFFINE) is now underway in men with moderate to severe haemophilia A.

References

George L, Eyster E, Ragni M, et al. Phase I/II Trial of SPK-8011: Stable and Durable FVIII Expression for >2 Years with Significant ABR Improvements in Initial Dose Cohorts Following AAV-Mediated FVIII Gene Transfer for Hemophilia A [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). Accessed September 30.