Laurence M. Corash
Analyst · Wedbush Securities
Thank you, Obi. Agreement to proceed forward with the PMA application is an important event in product development. Those who have followed the Cerus story for an extended time will appreciate just how pivotal an achievement this represents for the INTERCEPT platelet program. In 2001, we completed the Phase III Sprint trial, which included 645 patients enrolled across 12 U.S. sites supported with 4,719 platelet transfusions. The trial's primary endpoint was designed to assess the hemostatic efficacy of INTERCEPT platelets compared to conventional platelets for prevention and control of bleeding due to low platelet counts. The protocol also included multiple secondary endpoints for additional measures of both efficacy and safety. The Sprint trial met the primary efficacy endpoint. The INTERCEPT platelets were shown to be equivalent to conventional platelets according to a rigorous assessment of bleeding. However, upon submission of the clinical module to FDA in 2002, the FDA expressed concern regarding potential safety signals for several types of infrequent adverse events, including the important pulmonary event of acute lung injury. Data from the Sprint trial were used to support EU regulatory registrations. However, prior to launching the INTERCEPT platelet system in Europe, and in response to FDA's concerns, Cerus sponsored an independent blinded review of pulmonary adverse events reported in the Sprint trial. A panel of external pulmonary experts reviewed the primary medical records of all Sprint patients with pulmonary adverse events and concluded that there was no difference in the frequency of acute lung injury events. The review was submitted to FDA. However, it did not fully address FDA's concerns, and the agency requested that the frequency of pulmonary adverse events in patients supported with INTERCEPT platelets be confirmed in a second prospective clinical trial. Due to the low frequency of acute lung injury, the design of the study powered for these events proved to be extremely challenging. A statistically valid comparison for this safety endpoint requires a very large number of patients, beyond what Cerus believe logistically feasible. Over a period of 6 years, Cerus presented a number of potential trial designs to FDA to address their concerns. But we were unable to reach a mutually acceptable design. In parallel with FDA discussions, following the launch of INTERCEPT platelets in Europe, we initiated a post-marketing haemovigilance program to obtain safety data in routine use. In addition, we carefully monitored the safety surveillance data collected by independent haemovigilance programs conducted by regulatory authorities in France and Switzerland. During the years these data were being collected, Cerus continued to discuss with the FDA the possibility that European haemovigilance data could satisfy their concerns and enable us to move forward without conducting an additional safety study. This week, after 10 years of experience and more than 1 million INTERCEPT platelet transfusions in Europe, we reviewed with FDA the aggregate haemovigilance data obtained by EU regulatory authorities for over 130,000 INTERCEPT platelet transfusions in France and Switzerland. This included a recent presentation by Swissmedic for 62,500 INTERCEPT platelet transfusions over 2 years in which they showed a reduction in severe adverse events, including respiratory events after national adoption of INTERCEPT platelets. In consideration of this body of haemovigilance data, in conjunction with the prior U.S. data and the EU randomized clinical trial data, FDA agreed that the combined data were sufficient to file a PMA for INTERCEPT platelets without conducting another prospective clinical trial. Also we will be working with FDA to define a Phase IV postmarketing study plan, which will be included in our PMA submission. Now I'd like to turn the call over to Carol Moore who will provide you with further comments about our FDA progress, as well as an update on our other development programs.