Image courtesy of NIGMS
A UK regulatory agency has lifted the hold placed on a phase 1/2 study of the gene therapy BMN 270 in patients with hemophilia A.
Dosing was suspended in this trial after the first 9 patients were enrolled, but the Medicines and Healthcare Products Regulatory Agency (MHRA) has decided the study can continue.
BioMarin Pharmaceutical Inc., the company developing BMN 270, said the trial should resume enrollment by the end of this year.
BMN 270 is a recombinant adeno-associated virus vector coding for human coagulation factor VIII (FVIII).
The phase 1/2 study of BMN 270 was designed to evaluate the safety and efficacy of the therapy in up to 15 patients with severe hemophilia A.
Results in 7 patients on this study were recently presented at the World Federation of Hemophilia 2016 World Congress.
However, after the study had enrolled 9 patients, dosing of BMN 270 was suspended due to increases in alanine aminotransferase levels that exceeded a pre-specified threshold.
Following the suspension, BioMarin reviewed safety and efficacy data on the 9 patients with the MHRA. Based on this review, the MHRA approved resumption of the study.
The agency also approved the company’s proposed amendments to the study, which included eliminating the requirement for prophylactic corticosteroids and increasing potential additional enrollment from up to 3 additional patients to up to 6 additional patients.
BioMarin said it intends to resume enrollment in the study before the end of 2016. Based on protocol amendments, 3 patients will be enrolled at a dose of 4 x 1013 vg/kg, and an additional 3 patients may be enrolled at this dose or the previously tested high dose of 6 x 1013 vg/kg.
In the up to 6 additional patients, the requirement for prophylactic corticosteroids has been removed, and the threshold for starting therapeutic corticosteroids has been increased.
BioMarin said safety and efficacy data from these patients will inform the phase 2b study expected to begin in the second half of 2017.
“We are pleased that MHRA has approved the resumption of enrollment of the BMN 270 study, as well as the study amendments,” said Hank Fuchs, MD, chief medical officer at BioMarin.
“We believe that the amendments will allow us to optimize the design of a robust phase 2b clinical trial, which potentially could support an accelerated approval by health authorities. We are grateful to the patients who are participating in this current study and are encouraged by the results so far for this phase 1/2 trial.”
