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Alnylam Pharmaceuticals, Inc. (ALNY), a leading RNAi therapeutics company, announced today that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) has granted Orphan Drug Designations for ALN-AT3 as an orphan medicinal product for the treatment of hemophilia A and hemophilia B. Alnylam is developing ALN-AT3, a subcutaneously administered RNAi therapeutic targeting antithrombin (AT), for the treatment of hemophilia and other Rare Bleeding Disorders (RBD).

“We are very pleased to have received Orphan Drug Designations from the EMA COMP for ALN-AT3, a key program in our ‘Alnylam 5×15’ product development and commercialization strategy. We believe that our subcutaneously delivered RNAi therapeutic represents an innovative approach for the management of hemophilia and has great potential to make a meaningful impact in the treatment of this often debilitating bleeding disorder,” said Saraswathy (Sara) Nochur, Ph.D., Senior Vice President, Regulatory Affairs and Quality Assurance at Alnylam. “Having announced positive top-line results in adult healthy volunteers earlier this year, we look forward to presenting initial Phase 1 results, including data in hemophilia subjects, later in the year.”

ALN-AT3 is currently being investigated in a multinational Phase 1 trial. At the World Federation of Hemophilia 2014 World Congress held in May, Alnylam presented positive top-line data from Part A of the study performed in adult healthy volunteers. Initial results from the sole dose cohort enrolled (n=4; 3:1, drug:placebo) showed that a single, low subcutaneous ALN-AT3 dose of 0.03 mg/kg resulted in an up to 28-32% knockdown of AT at nadir (p < 0.01 by ANOVA, relative to placebo).

This resulted in a statistically significant (p < 0.01) increase in peak thrombin generation, that was temporally associated and consistent with the degree of AT knockdown. ALN-AT3 was found to be well tolerated with no significant adverse events reported. With these data and in light of a dose escalation stopping rule at a 40% level of AT knockdown, the company has transitioned to Part B of the study – an open-label, multi-dose, dose-escalation study enrolling up to 18 people with moderate to severe hemophilia A or B.

The primary objective of this part of the study is to evaluate the safety and tolerability of multiple doses, specifically three weekly doses, of subcutaneously administered ALN-AT3 in hemophilia subjects. Secondary objectives include assessment of clinical activity as determined by knockdown of circulating AT levels and increase in thrombin generation at pharmacologic doses of ALN-AT3. In this part of the study, dose escalation will be allowed to proceed beyond the 40% AT knockdown level. The company plans to present initial clinical results, including results in hemophilia subjects from Part B of the study, by the end of the year.

Orphan Drug Designation by the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than five in 10,000 persons in the European Union (EU), and where no satisfactory treatment is available. In addition to a 10-year period of marketing exclusivity in the EU after product approval, Orphan Drug Designation provides incentives for companies seeking protocol assistance from the EMA during the product development phase, and direct access to centralized marketing authorization.

Click here to read this Alnylam Pharmaceuticals press release in its entirety. 

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