BioMarin Announces Interim Analysis of INSPIRE Clinical Trial in Pompe Disease, Encouraged By Positive Trends In Trial

BioMarin Pharmaceutical Inc. BMRN today announced interim results from INSPIRE, a Phase 2 trial for reveglucosidase alfa, a fusion protein of insulin-like growth factor 2 and acid alpha-glucosidase (IGF2-GAA) being studied for the treatment of late-onset Pompe disease (LOPD). The interim efficacy and safety analysis is based on 24 patients who previously had been on treatment with the enzyme replacement therapy, alglucosidase alfa, and were switched to reveglucosidase alfa. Investigators indicated that, while on treatment with alglucosidase alfa, the majority of the patient population were considered to have worsening of their Pompe disease over the last 12 months. At week 24, the 18 patients on treatment with reveglucosidase alfa and who completed the study demonstrated respiratory muscle improvements with a mean increase of 2.2 points from baseline in percent predicted Maximal Inspiratory Pressure (MIP) and a mean increase of 3.1 points from baseline in percent predicted Maximal Expiratory Pressure (MEP). Patients completing the study also experienced a mean improvement of 26.1 meters in 6 Minute Walk Test (6MWT). In the 14 patients who met eligibility at both screening and baseline and completed the study, a mean increase of 3.8 points from baseline in percent predicted MIP also was observed. The 18 patients completing the study showed a mean decrease of 3.7 points from baseline in percent predicted Forced Vital Capacity (FVC), but were considered relatively unchanged from screening at -0.7 points in percent predicted. BioMarin will present these data at an upcoming medical meeting. "We are encouraged by the positive trends in respiratory muscle strength as measured by pressures, which may indicate a possible halt in decline or improvement in lung capacity and endurance in late-onset Pompe disease," said Hank Fuchs, M.D., Executive Vice President and Chief Medical Officer at BioMarin. "Reveglucosidase alfa has the potential to be an additional choice for Pompe patients, and we look forward to working with health authorities and the patient community to advance this experimental therapy to the next stage of clinical development." "Pompe is a progressive and debilitating disease, and patients need additional treatment options. The reveglucosidase alfa data appears promising and could be a potential new enzyme replacement therapy that could make a meaningful difference to late-onset Pompe patients," said Professor Benedikt Schoser of the Friederich-Baur Institute and speaker of the German working group for Pompe disease. TABLE 1: Reveglucosidase Alfa Interim Phase 2 Study Results Endpoint N Baseline (SD) Week 24 (SD) Mean change from baseline to week 24 (SD) MIP - mean % predicted 18 50.0 (17.5) 52.1 (15.9) 2.2 (8.3) MEP - mean % predicted 18 38.9 (12.3) 42.0 (12.1) 3.1 (8.7) 6MWT - mean meters 17 345.8 (95.3) 371.9 (114.2) 26.1 (40.6) FVCupright- mean % predicted 18 60.7 (15.1) 56.9 (14.2) -3.7 (4.4) Only patients with baseline and week 24 results are included 3.8% (6.4) absolute improvement per protocol analysis of MIP (14 patients who met eligibility at screening and baseline) FVC change from screening -0.7% TABLE 2: Reveglucosidase Alfa Interim Phase 2 Study Baseline Characteristics Baseline characteristic 701-301 (N=23)* Age – mean yrs (range) 48.5 (19-69) Sex- M/F % 48/52 Time on alglucosidase alfa – mean years (SD) 5.5 (2.7) MIP – mean % predicted (SD) 51.2 (17.2) MEP – mean % predicted (SD) 40.9 (12.1) 6MWT – mean meters (SD) 317.7 (102.3) FVC Upright – mean % predicted (SD) 60.7 (15.9) Use of walking aids in 6MWT- % 34.8 Use of ventilatory support- % 34.8 *One patient was excluded due to inclusion violation of not being diagnosed with LOPD. Safety Six patients discontinued treatment early, and two patients experienced serious adverse events. Hypoglycemia was generally similar in frequency and severity as in the previous study, and the overall pattern of safety was otherwise consistent with experience using other enzyme replacement therapy. INSPIRE Study Design The INSPIRE clinical trial is a Phase 2 single-arm, open-label, switchover study of reveglucosidase alfa in patients with late-onset Pompe disease (LOPD) who have been receiving treatment with recombinant human acid alpha glucosidase (rhGAA) for 48 weeks or longer. This study was changed from a Phase 2/3 to a Phase 2 study to allow use of drug employing a new purification process, which could be used in an anticipated Phase 3 registration-enabling trial. All patients in the study have been transferred to the new material, and all future patients will be treated with the new material. Ambulatory patients who have mild to moderate respiratory impairment will switch directly to receive reveglucosidase alfa 20 mg/kg by IV infusion every other week. The change in value in primary endpoint, Maximum Inspiratory Pressure (MIP), and secondary endpoint, Maximum Expiratory Pressure (MEP), Forced Vital Capacity (FVC) Upright and Six-Minute Walk Test (6MWT) will be measured as the difference between the Baseline value and the Week 24 value within each individual subject. The study has a 24-week treatment period followed by an extension period of up to 240 weeks.