Achillion Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for danicopan (ACH-4471) for treatment in combination with a C5 monoclonal antibody for patients with paroxysmal nocturnal hemoglobinuria (PNH) who are sub-optimal responders to a C5 inhibitor alone. The FDA’s decision was based on positive safety and efficacy data from the ongoing danicopan Phase 2 PNH combination trial. Interim data was reported at the New Era of Aplastic Anemia and PNH Meeting in May 2019. The top line data from this combination trial is expected in the fourth quarter of 2019. FDA Breakthrough Therapy designation is designed to expedite the development and review of medicines for serious or life-threatening conditions. Receiving Breakthrough Therapy designation from the FDA indicates preliminary clinical evidence has demonstrated the drug may provide substantial improvement on at least one clinically significant endpoint compared with currently available therapy. The benefits of this Breakthrough Therapy designation include more intensive guidance from FDA on an efficient drug development program, access to a scientific liaison to help accelerate review time and eligibility for Accelerated Approval and Priority Review if relevant criteria are met. Danicopan (ACH-4471) has previously received orphan drug designation for the treatment of PNH in 2017. Paroxysmal Nocturnal Hemoglobinuria (PNH): PNH is a rare, acquired blood disease caused by a somatic mutation resulting in the absence of key receptors, CD55 and CD59, on the surface of red blood cells (RBCs). The alternative pathway (AP) of the complement system recognizes these unprotected RBCs as foreign and destroys them in the circulatory system (intravascular hemolysis) and in the liver or spleen (extravascular hemolysis). The current standard of care for PNH targets intravascular hemolysis by inhibiting C5 complement protein (C5), leaving some patients with persistent extravascular hemolysis from early phases of complement activation (AP Activity) which C5 inhibition cannot address leaving patients with partial control of their PNH. Up to 75% of PNH patients treated with C5 inhibitors remain anemic during treatment, with up to one-third of those patients reporting the need for blood transfusions within the last year. Factor D is the critical, rate-limiting protein within the AP. By targeting Factor D, proximal AP inhibition may disable both downstream terminal complement activation (IVH) and upstream C3 fragment opsonization (EVH). Achillion is developing a potentially more complete approach to PNH with factor D inhibition to selectively block alternative pathway activity and protect against both destructive processes of RBCs in PNH with convenient oral therapies.