MENU

Complement-Mediated Disease

The complement system plays a central role in the body’s immune system as a protective mechanism for host defense, but its dysregulation results in serious, life-threatening complications in a broad range of human diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic-uremic syndrome (aHUS), neuromyelitis optica, and myasthenia gravis (MG), amongst others.

Complement component C5 – which is predominantly expressed in liver cells – is a genetically and clinically validated disease target. Human mutations resulting in C5 deficiencies are associated with an attenuated immune response against certain infections. Intravenous anti-C5 monoclonal antibody therapy (eculizumab) has demonstrated clinical activity and tolerability in a number of complement-mediated diseases. It is approved for the treatment PNH and aHUS in the U.S., Europe and other countries.

show more

ALN-CC5 for the Treatment of Complement-Mediated Disease

ALN-CC5 is in clinical development as an investigational, subcutaneously administered RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated disease. ALN-CC5 utilizes our proprietary Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology enabling subcutaneous dosing with increased potency and durability, and a wide therapeutic index. We believe that a subcutaneously administered RNAi therapeutic that silences C5 represents a novel approach to the treatment of complement-mediated diseases.

We believe that ALN-CC5—as a first-in-class C5 synthesis inhibitor—represents an innovative, differentiated, and well-validated approach for the treatment of complement-mediated diseases. Further, we believe that a new medicine to treat excessive complement activity that could be given by infrequent, subcutaneous administration would be a welcome addition to the treatment landscape, and we look forward to the continued clinical advancement of this novel investigational therapeutic.

Please read the latest press releases and data presentations for ALN-CC5 here.

Less Content

Initial Data in Paroxysmal Nocturnal Hemoglobinuria Patients from Ongoing Phase 1/2 Clinical Study with ALN-CC5 Support Potential for Eculizumab Sparing and Improved Disease Control for Eculizumab Inadequate Responders

Initial Data in Paroxysmal Nocturnal Hemoglobinuria Patients from Ongoing Phase 1/2 Clinical Study with ALN-CC5 Support Potential for Eculizumab Sparing and Improved Disease Control for Eculizumab Inadequate Responders

We reported data from 6 patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) enrolled in Part C of our ongoing Phase 1/2 clinical study with ALN-CC5, an investigational RNAi therapeutic targeting complement component 5 (C5) for the treatment of complement-mediated diseases. These data were presented at the 21st Congress of the European Hematology Association (EHA) Meeting in Copenhagen, Denmark, held June 9-12, 2016.  In this part of the study, ALN-CC5 was evaluated as a monotherapy or as an adjunct to eculizumab, an approved anti-C5 monoclonal antibody indicated for the treatment of PNH.



Read More

Updated Healthy Volunteer Data from Phase 1/2 Clinical Study with ALN-CC5 for the Treatment of Complement-Mediated Diseases

Updated Healthy Volunteer Data from Phase 1/2 Clinical Study with ALN-CC5 for the Treatment of Complement-Mediated Diseases

We reported updated data from our ongoing Phase 1/2 clinical study with ALN-CC5, an investigational RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases. Data were presented at the 53rd Congress of the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) in Vienna, Austria, held May 21-24, 2016.  Results showed that administration of ALN-CC5 in healthy volunteers (N=44) achieved up to 99% knockdown of serum C5 and a mean maximum of 86% serum hemolysis inhibition in the highest dose group, with mean levels consistently greater than 80% inhibition through the 13 weeks of treatment. Results also showed a mean maximum CH50 inhibition of 99.6% and maximum inhibition up to 100% relative to baseline.

The effects of ALN-CC5 were found to be highly durable, with C5 knockdown clamped at over 90% for more than six months following a single dose. C5 knockdown and complement inhibition results support the potential for a once-quarterly dosing regimen when used in combination with the monoclonal antibody, eculizumab. Importantly, ALN-CC5 was shown to be generally well tolerated, with no serious adverse events and no drug-related discontinuations to date. All adverse events were mild or moderate in severity.


Read More

Positive Interim Results from Phase 1/2 Clinical Study with ALN-CC5 for the Treatment of Complement-Mediated Diseases

Positive Interim Results from Phase 1/2 Clinical Study with ALN-CC5 for the Treatment of Complement-Mediated Diseases

We reported new data from our ongoing Phase 1/2 clinical study with ALN-CC5, an investigational RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases. Data were presented at the American Society of Hematology (ASH) 2015 Annual Meeting, held December 5 – 8, 2015.  Results showed that administration of ALN-CC5 achieved up to 99% knockdown of serum C5 and up to 98% inhibition of serum hemolytic activity, an assay for complement activity.  Further, ALN-CC5 administration resulted in low levels of residual C5, which – based on comparisons from separate studies – were at or below the estimated levels of free C5 observed at therapeutic doses of eculizumab, an approved anti-C5 monoclonal antibody. The effects were also found to be highly durable, with C5 knockdown and complement inhibition results supporting a once monthly and possibly a once quarterly subcutaneous dose regimen.  Importantly, ALN-CC5 was shown to be generally well tolerated, with no clinically significant, drug-related adverse events to date.




Read More