Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare life-threatening disease characterized by destruction of red blood cells, blood clots, and compromised bone marrow function. Some of the symptoms of the disease include abdominal and back pain, dark urine, easy bruising or bleeding, fatigue or weakness, headache and shortness of breath. The risk factors for PNH include age, obesity and hormone therapy. According to the Johns Hopkins Medicine, approximately, one to one and a half persons per million of the population are affected by PNH globally with a predominance in young adults. PNH is also associated with aplastic anemia and up to 30% of newly diagnosed cases of PNH progress from aplastic anemia. Treatment of PNH includes bone marrow transplantation and the only medicine approved by the USFDA for its treatment is eculizumab (Soliris), manufactured by Alexion Pharmaceuticals, Inc.
The main growth drivers of the pipeline for PNH include increasing awareness and research funding from various non-profit organizations for the discovery and development of drugs for PNH, rising prevalence of aplastic anemia, innovations in genetic engineering and introduction of novel gene therapies, increasing knowledge of pathophysiology of thrombosis and discoveries of novel anticoagulants, price skimming and niche market opportunity.
In September 2016, Alexion Pharmaceuticals Inc. started a Phase III, randomized, open-label, active-controlled study of ALXN1210 versus eculizumab in complement inhibitor-naïve adult patients with PNH. ALXN1210 is a longer-acting anti-C5 antibody and is being evaluated for the treatment of patients with PNH. This study is expected to be completed in December 2017. In January 2015, Alnylam Pharmaceuticals Inc., began a Phase I/II study of subcutaneously administered ALN-CC5 in healthy adult volunteers and patients with PNH. ALN-CC5 is an RNAi therapeutic which targets the C5 component of the complement pathway. The study was expected to complete by December 2016, however, it is still ongoing. In February 2016, Akari Therapeutics plc initiated a Phase II trial evaluating Coversin in PNH in patients with resistance to eculizumab due to complement C5 polymorphisms. Coversin is a second-generation complement inhibitor which prevents release of C5a and formation of C5b–9. The trial is expected to complete in December 2018.
In March 2017, Achillion Pharmaceuticals, Inc. started a Phase II open-label proof of concept study to assess the efficacy of ACH-0144471 in untreated patients with PNH. ACH-4471 is a specific factor D inhibitor which has shown significant reduction in hemolysis in patients with PNH. The study is expected to complete in August 2017. In November 2015, Apellis Pharmaceuticals, Inc. initiated a Phase Ib study to assess safety and efficacy of subcutaneous APL-2 in patients with PNH. The study is expected to complete in December 2017. APL-2 is a conjugate of APL-1, a synthetic cyclic peptide that inhibits C3. APL-2 is intended for intravitreal and subcutaneous route of administration. In December 2016, APL-2 received fast track designation in PNH from the USFDA. In February 2017, Ra Pharmaceuticals Inc. began advancing RA101495 into a Phase 2 clinical trial in patients with PNH. RA101495 is a C5 inhibitor intended for subcutaneous injection for the treatment of PNH. The trial is expected to complete in February 2018. In October 2016, the company had filed for an IPO to fund the clinical development of RA101495.
Some of the companies involved in the development of drug candidates for PNH include Alexion Pharmaceuticals Inc., Alnylam Pharmaceuticals Inc., Akari Therapeutics plc, CMIC Co, Ltd. Japan, Achillion Pharmaceuticals, Inc., Apellis Pharmaceuticals, Inc., and Ra Pharmaceuticals Inc.