© 2021 MJH Life Sciences and HCPLive-Clinical news for connected doctors. all rights reserved.
© 2021 MJH Life Sciences™ and HCPLive-Clinical news for connected doctors. all rights reserved.
Conference | American Society of Hematology
The data for the first and second phases of the Alta study were announced on ASH this weekend.
New data from a multicenter study in the United States found that a single infusion of giroctocogene fitelparvovec gene therapy in patients with severe hemophilia A is well tolerated.
The therapy is also associated with elevated factor VIII (FVIII) levels in the mild to normal range, and there were no persistent adverse events and minimal bleeding in the highest-dose cohort.
The research was presented at the American Society of Hematology (ASH) annual meeting and exposition.
Researchers led by Andrew D. Leavitt, MD, University of California, noted the rarity of hemophilia A, which is caused by a pathogenic event in the F8 gene.
However, adeno-associated virus (AAV)-mediated gene transfer allows the delivery of modified functional F8 coding sequences to hepatocytes, and subsequent levels of synthetic FVIII may prevent bleeding events in the absence of exogenous FVIII.
Therefore, Leavitt and colleagues introduced the latest situation of the Alta study's nearly two-year follow-up, which is an ongoing gene therapy study for these patient groups.
A total of 11 patients participated in the study, and one patient was excluded after not completing the 2-year follow-up.
Phase 1 and Phase 2 of the Alta study included a dose range study of the recombinant AAV serotype 6 vector giroctogene fitelparvovec, previously known as SB-525, which encodes a modified F8 coding sequence with B domain deletion.
Giroctocogene fitelparvovec was injected into adults over 18 years of age with severe hemophilia A at doses of 9e11, 2e12, 1e13, and 3e13 vg/kg in 4 cohorts (2 patients in each group).
The 3e13-vg/kg dose cohort was later expanded by 3 patients.
The researchers included safety, circulating FVIII activity, the use of FVIII replacement therapy, and the frequency of bleeding events as key endpoints of the study.
The deadline for the Alta study is set to May 19, 2021.
Leavitt and researchers reported that the most common treatment-related adverse events (AE; n/N [%]) included elevated liver enzymes and infusion-related reactions: elevated alanine aminotransferase (ALT; 5/11 [45.5%] Overall; 3/5 [60.0%] in the 3e13-vg/kg cohort), aspartate aminotransferase increased (AST; 3/11 [27.3%] overall; 2/5 [40.0%] in 3e13-vg/kg In the cohort), fever (3/11 [27.3%] overall; 3/5 [60.0%] in the 3e13-vg/kg cohort) and tachycardia (2/11 [18.2%] overall; in 3e13 -The queue is 2/5 [40.0%] vg/kg queue).
In addition, treatment-related serious adverse events were reported in a patient who developed hypotension and fever approximately 6 hours after giroctocogene fitelparvovec infusion. However, these events were completely resolved by treatment, and discharge from the hospital after the next day infusion was not delayed.
The team also reported that an elevated ALT requires >7 days of corticosteroid treatment
Four of the five patients in the 3e13-vg/kg cohort received tapered corticosteroids.
For the 4 patients in this cohort, the average FVIII activity of patients in the 3e13-vg/kg cohort remained in the mild to normal range during the 104th week.
In this cohort, the annualized bleeding rate 3 weeks after the study drug was 0 in the first year after infusion and 0.9 during the entire follow-up period.
In addition to the phase 1 and phase 2 data published on ASH, Leavitt and colleagues added, “A phase 3 study of giroctocogene fitelparvovec in hemophilia A patients (NCT04370054) is ongoing.”