Alnylam’s ALN-CC5 used as Adjunt Therapy for Paroxysmal Nocturnal Hemoglobinuria Showed Promising Initial Results

Alnylam Pharmaceuticals, a leading RNAi therapeutics company reported their initial result for an experimental drug called ALN-CC5. The clinical study showed that it can reduce the dose and frequency of eculizumab, a known treatment for paroxysmal nocturnal hemoglubinuria or PNH with a known side-effect of breakthrough hemolysis. The study supported their theory that ALN-CC5 can help improve the disease control of inadequate responders of eculizumab.

The company reported the initial results of the Part C of its ALN-CC5 Phase1 / 2 Clinical Trial in the 21st Congress of European Hematology Association in Copenhagen, Denmark. ALN-CC5 is administered subcutaneously; it is an investigational RNAi therapeutic targeting component of C5 which is used for the treatment of complement-mediated diseases.

The part C phase of the clinical trial evaluated the clinical activity and tolerability of ALN-CC5 in six patients suffering from paroxysmal nocturnal hemoglobinuria or PNH.  It is rare form of hematologic disease which is acquired through mutations in the PIG-A gene that leads to the destruction of complement-mediated red blood cells (RBC).

In the study, ALN-CC5 was given as a monotherapy or adjunct to eculizumab.  Eculizumab is an approved anti-C5 monoclonal antibody which is indicated for PNH treatment. Based from the preliminary study, ALN-CC5 was able to achieve a clamped knockdown of serum C5.  It can also lower lactate dehydrogenease or LDH which is used for biomarker for RBC hemolysis in patients suffering PNH.

The study also further supports the development of ALN-CC5 to reduce the frequency and dose of eculizumab for patients with PNH.   It also showed that it can potentially improve the disease control in patients with poor response to eculizumab. Alnylam plans to start the Phase 2 trial later this year.

Akshay Vaishnaw, M.D., Ph. D., Chief Medical Officer of Alnylam and Executive Vice President of R & D noted in a press release statement that based from the preliminary data of patients undergoing the Phase 1/ 2 clinical study, the results suggests that ALN-CC5 has the potential to change the therapeutic management of PNH. It can clamp the inhibition of hepatic C5 synthesis which provides the foundation for reduced doses and frequency of anti-C5 monoclonal antibody therapy.

Based from the results, Vaishnaw believes on the durability of ALN-CC5 action – once quarterly subcutaneous injection of this drug can reduce the frequency and dosage of eculizumab.  They are also looking forward to evaluate these two drugs further in their ongoing Phase 1/ 2 study and Phase 2 trial in patients with PNH.

The company also plans to evaluate ALN-CC5 as a monotherapy drug in targeting other complement-mediated diseases.  The trial to test if it is applicable for monotherapy is expected to start by 2017.

Anita Hill M.D, PhD, MRCP, FRCPath, Lead for the National PNH Service in England and Consultant Hematologist for Leeds Teaching Hospitals, NHS Trust, UK, said in an interview that the dysregulated complement activity is the cause of many diseases including PNH.  Eculizumab is known to be effective in treating PNH but a significant number of patients suffer from breakthrough hemolysis which is a known side effect of the drug.

This effect has an impact on the economic burden of the government.  Thus, having a maintenance schedule for biweekly intravenous treatment would be a great help for the patients suffering from PNH. Hill also added that the preliminary data from the study provided additional evidence on the potential of having a long-term treatment for patients with PNH. Hill and her team shared their excitement in exploring their theory.

Bottom line

The positive result of Alnylam’s initial trial will help patients suffering from PNH to have a reduce chance of having breakthrough hemolysis. The possibility of having combination therapy will improve the efficacy of Eculizumab while reducing its side-effects.

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