Updated Results from Phase 1/2 Study of ALN-CC5 in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

We reported new results from Part C of our Phase 1/2 clinical study of ALN-CC5, a subcutaneously administered investigational RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases, at the 58th Annual Meeting of the American Society of Hematology (ASH), held December 3 – 6, 2016 in San Diego, California.

New results from Part C provided continued evidence that ALN-CC5-mediated knockdown of serum C5 has the potential to enable effective sparing of eculizumab in patients with PNH.  As of the data transfer date of October 13, 2016, results showed that PNH patients who had previously been naive to eculizumab (N=3) achieved sustained control of disease hemolysis with normalization of lactate dehydrogenase (LDH) to less than or at approximately 1.5 times upper limit of normal (ULN) for up to 6 months while on a spared eculizumab regimen of 600 mg every 4 weeks.  For patients who entered the study on background eculizumab (N=3), effective disease control with normalization of LDH to less than or at approximately 1.5 times ULN was achieved for up to 5 months while on a spared once-monthly regimen of 900 mg eculizumab.  Using an assay for eculizumab plasma levels, both sparing regimens achieved stable eculizumab trough levels greater than 100 mcg/mL during the 5 to 6 month period.

As previously reported, ALN-CC5 was generally well tolerated in patients with PNH after multiple doses for up to 16 weeks of dosing.  During the course of spared eculizumab dosing, as of the data transfer date of October 13, 2016, there were no serious adverse events (SAEs) or discontinuations due to adverse events (AEs) in the study, and the majority of reported AEs were mild or moderate in severity.  One patient developed an episode of breakthrough hemolysis in the setting of an upper respiratory tract infection; this AE was moderate in severity and was considered unrelated to study drug by the investigator.

We believe ALN-CC5, both as monotherapy and in combination with anti-C5 monoclonal antibodies, represents an opportunity to transform the management of complement-mediated diseases by achieving clamped inhibition of hepatic C5 synthesis. We look forward to further exploring the therapeutic potential of ALN-CC5 through future studies in PNH and other complement-mediated diseases, such as Atypical Hemolytic Uremic Syndrome (aHUS) and Myasthenia Gravis (MG).