Inspiration Biopharmaceuticals, Inc. (Inspiration) announced interim clinical results for the company's two lead product candidates, an intravenous recombinant porcine FVIII (OBI-1) in the treatment of serious bleeds in acquired hemophilia A (AHA) and an intravenous recombinant FIX (IB1001) for the treatment and prevention of bleeding in children less than 12 years of age with hemophilia B. The data were presented in posters at the 54th American Society of Hematology Annual Meeting in Atlanta, Georgia.
Inspiration's OBI-1 investigational drug met the primary endpoint of providing effective or partially effective treatment of serious bleeding in 16 subjects with acquired hemophilia A based on the investigator's assessment of response to treatment.
The poster titled, "Recombinant B-domain deleted porcine FVIII (OBI-1) safety and efficacy in acquired hemophilia A: interim results", described interim results from the prospective Phase 2/3 trial of the administration of OBI-1 in the treatment of serious bleeds. Sixteen AHA subjects and 1 compassionate use subject with AHA all had successful control (either effective or partially effective) of serious hemorrhage at 24 hours post the initial dose of OBI-1 and subsequent resolution of their bleed. Therapeutic FVIII levels were achieved with peak levels above 100% and maintained with intermittent OBI-1 administration determined by the peak FVIII and fall-off blood levels. In three subjects who developed anti-OBI-1 titers there was no correlation to the anti-hFVIII titers or clinical response as evaluated by FVIII levels and the resolution of bleeding. The mean immediate (20 minute) post-infusion factor VIII level was 230% and, given an initial dose of 200 U/kg, indicated an incremental recovery of about 1.15 IU/dL per IU/kg. There were 11 serious adverse events through September 2012 and 5 deaths were reported. None of the deaths were attributed by the investigator to OBI-1 treatment. One serious adverse event (pneumonia and atrial fibrillation) was deemed by the investigator to be probably not/remotely related to OBI-1. Antibodies to OBI-1 developed in 3 subjects, but all responded favorably to treatment. No specific treatment was given for the anti-OBI-1 antibodies. These interim results suggest that in this study OBI-1 was well-tolerated and effective in the treatment of serious bleeding episodes in AHA. Authors of the study included Jean St.-Louis MD, Rebecca Kruse-Jarres MD, Anne Greist MD, Amy Shapiro MD, Hedy Smith MD, Pratima Chowdary MD, Anja Drebes MD, Jay Lozier MD, and Edward Gomperts MD.
Inspiration intends to file a biologics license application (BLA) for OBI-1 in the first half of 2013. OBI-1 has received orphan drug designation in the US and EU, and was recently granted fast track designation by the United States Food and Drug Administration (FDA).
In addition, Inspiration's IB1001 demonstrated an average in vivo recovery of 0.69±0.21 (mean±SD) in the 7 subjects < 12 years of age with hemophilia B versus that seen in adults (age 12 years and older) of 0.98±0.22 (mean±SD) previously reported by Martinowitz U, et al. (ref. Haemophilia, 18, 2012).
The poster titled, "IB1001, an investigational recombinant factor IX, pharmacokinetics in pediatric patients with hemophilia B", reports preliminary pharmacokinetic (PK) data from 7 subjects (4 between 6 and 12 years of age and 3 less than 6 years of age) who underwent a 72-hour PK assessment followed by treatment with IB1001. Compared to the findings previously reported with IB1001 by Martinowitz U, et al. in adult subjects 12 years of age and older, these pediatric subjects demonstrated a more rapid metabolism of factor IX with a shorter terminal half-life (mean±SD of 19.3±7.8 h vs. 29.6±18.2 h in adults), a smaller AUC 0-∞ (mean±SD of 1059±264 vs. 1668±598 in adults), and a lower in vivo recovery (mean±SD 0.69±0.21 vs. 0.98±0.22 in adults). These results are similar to those reported by Berntorp, et al (Haemophilia, 7, 2001) with nonacog alfa. Authors of the study were Shashikant J. Apte, M.D.; Uptal Chowdari, MD; M Joseph John, MD; Ri Liesner, MD; Vijay Ramanan, M.D.; Amy Shapiro, MD; Bonnie Mills, PhD; Edward Gomperts, MD; and Martin Lee, PhD.
Inspiration filed a marketing authorization application in Europe for IB1001 late 2011 and the regulatory review is ongoing. Subsequently, Inspiration filed a biologics license application in the United States for IB1001 in the first half of 2012 and the regulatory review is ongoing. The FDA placed a clinical hold on IB1001 in July 2012 when a number of study subjects developed antibodies to the host cell protein, Chinese Hamster Ovary cell proteins (CHOP), of IB1001. No clinical sequelae were associated with these antibodies and they did not impact the clinical effectiveness of the investigational product. Inspiration has made significant progress in addressing the situation, and intends to submit data to the FDA in the first part of 2013 to respond to the clinical hold.