New data boost Pfizer, Sangamo hemophilia A gene therapy

Sangamo CEO Sandy Macrae
Sangamo CEO Sandy Macrae. (Sangamo)

Pfizer and Sangamo Therapeutics have shared an upbeat update on their hemophilia A gene therapy. The update features evidence of the durability of responses to SB-525 and an early look at results in two recently treated patients, adding to the impression that the gene therapy is a threat to assets including BioMarin’s valrox and Spark Therapeutics’ SPK-8011. 

SB-525 is designed to deliver a copy of the Factor VIII gene to a patient’s liver cells, thereby enabling them to produce the protein at the root of hemophilia A. If effective, the gene therapy will raise FVIII levels, freeing patients from the burden of managing their disease and the symptoms it causes. 

In April, Sangamo suggested the gene therapy may live up to that promise by revealing data from the first two patients to receive the highest dose of SB-525. Now, Sangamo has followed up with data on the next two patients to take the highest dose, plus an update on the performance of other people treated in the 10-subject clinical trial.

One of the two recently-treated patients attained normal FVIII activity seven weeks after treatment. The other patient was yet to hit that milestone as of the data cutoff but received the treatment more recently. Sangamo said the patient’s FVIII activity kinetics appear consistent with those of the first two subjects to receive the higher dose.

Sangamo also shared an update on the first two patients to receive the higher dose. As of the cutoff, Sangamo had 19 to 24 weeks of follow up on the patients. FVIII activity in both patients remained in the normal range as of the cutoff. None of the high-dose patients have suffered bleeding events.

The patients have suffered adverse events, though. Two subjects experienced elevations in liver enzymes that were managed with steroids. These patients maintained FVIII expression.

Collectively, the safety and efficacy data suggest SB-525 is competitive, although longer-term follow up is needed to gauge whether the gene therapy can deliver the desired safe, one-shot treatment of hemophilia A. 

BioMarin has more follow up on its rival gene therapy, valrox, and is positioned to beat Sangamo to market. However, the BioMarin data suggest there is room to improve on valrox, notably because FVIII activity fell to 20% of normal by the time of the three-year readout. 

Spark also has a candidate in early-phase development but it is yet to deliver efficacy data showing it can rival SB-525. And it comes with immunogenicity concerns that forced physicians to reactively administer oral steroids and led Spark to start assessing the prophylactic use of steroids.