Alexion Pharmaceuticals, Inc. reported positive preliminary six month interim results from Shepherd, its second phase III trial testing Soliris (eculizumab) in a broader population of Paroxysmal Nocturnal Hemoglobinuria ("PNH") patients.
Shepherd is an open-label, non-placebo controlled 12 month Phase III PNH study which is primarily focused on examining safety, as well as efficacy measures. Interim results show that Soliris (eculizumab) appeared to be safe and well tolerated.
All pre-specified primary and secondary efficacy endpoints in the international trial were achieved with statistical significance. The pre-specified primary surrogate of efficacy endpoint was intravascular haemolysis, the underlying disease process and primary clinical manifestation in PNH, as measured by lactate dehydrogenase area under the curve (LDH AUC). The LDH AUC was significantly decreased (P<0.00000000001); LDH was reduced by 87 per cent from a median of 2051 at baseline to 270 U/L after 26 weeks. The most frequent adverse events with Soliris (eculizumab) were headache, nasopharyngitis, and nausea.
PNH, a rare form of haemolytic anaemia, is an acquired genetic blood disorder characterized by destruction of red blood cells by the body's complement system (a component of the immune system). Patients with PNH lack naturally-occurring complement inhibitors which normally prevent red blood cell destruction. Soliris (eculizumab), a long-acting C5 terminal complement inhibitor, is a monoclonal antibody drug that selectively blocks terminal complement activation. There currently is no approved therapy specifically available for treatment of PNH.
Shepherd enrolled 97 patients at 33 sites in the US, Canada, Europe and Australia. Both of the pre-specified secondary efficacy endpoints in SHEPHERD, reduction in mean LDH change from baseline and quality of life as measured by the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-Fatigue) instrument, were also achieved with statistical significance.
"The preliminary results observed with Soliris in the open-label phase III Shepherd PNH study are comparable to, and support the efficacy and safety observed with Soliris treatment in previous PNH trials," said Leonard Bell, M.D., chief executive officer of Alexion. "The Shepherd patients are a very heterogeneous population and the encouraging Soliris results in this population provide important support for the potential utility of Soliris treatment of PNH patients. We continue to target submission of marketing applications for Soliris in PNH during the second half of this year and we look forward to providing a further update this summer regarding our plans with U.S. and European regulatory agencies."
Alexion previously reached an agreement with the FDA on the design of Triumph, a pivotal phase III efficacy trial with Soliris (eculizumab) in PNH patients, and the companion phase III Shepherd trial, under the FDA's Special Protocol Assessment (SPA) process. Shepherd is an open-label, non-placebo-controlled, multi-centre clinical trial primarily aimed at generating safety data with Soliris (eculizumab) in a broader population of haemolytic PNH patients. Efficacy measures are also being obtained in the study. The Shepherd protocol includes 12 months of treatment with a six-month interim analysis. It is expected that data from these trials will serve as the primary basis of FDA review for the approval of a Biologics License Application (BLA) for Soliris (eculizumab) in the PNH indication, as well as the primary basis of review for a European Marketing Authorization Application (MAA). Soliris (eculizumab) has been granted Orphan Drug Status from both the U.S. and European regulatory agencies to treat PNH.
Based upon scientific investigations and presentations of the prevalence of patients diagnosed with abnormal PNH cells in their blood, it is currently estimated that approximately 8,000 - 10,000 people in North America and Europe suffer from PNH. Patients with PNH may suffer from severe haemolysis, anaemia, chronic fatigue, recurrent pain, pulmonary hypertension and intermittent episodes of dark coloured urine, known as hemoglobinuria. Importantly, PNH patients are at increased risk of forming life-threatening blood clots, or thromboses, which are a significant cause of death in this disease.