Alnylam launches study to support its rare disease candidate ALN-AS1

RNAi leader Alnylam ($ALNY), the American Porphyria Consortium and The European Porphyria Network are launching the Explore observational study of patients with the rare disease, with the hope of advancing Alnylam's candidate for porphyria, with a goal of filing for approval in late 2014 or early 2015.

The candidate, ALN-AS1, targets the gene encoding aminolevulinic acid synthase 1 (ALAS 1) using the RNA interference treatment paradigm. It aims specifically at hepatic porphyrias, a subset of the condition in which the inherited deficiency of a certain enzyme (uroporphyrinogen decarboxylase) occurs within the liver.

Alnylam focuses on diseases of the liver because that is where drug delivery of the RNAi molecules has proven most feasible. Like the company's other candidates, ALN-AS1 uses the Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform, enabling subcutaneous delivery.

"With the initiation of Explore, we aim to learn more about the clinical course, management, and overall disease burden through patient and physician assessments, in addition to a number of laboratory analyses, for patients with hepatic porphyrias. We believe that these results could give us critical insights in the disease course and management of porphyria, improving our ability to better design trials for our ALN-AS1 investigational therapy," said senior director of clinical development Dr. Amy Simon in a statement.

The study aims to learn more about patients with hepatic porphyria, including its clinical management, signs and symptoms, toxic intermediates and expression levels of certain molecules. Symptoms of the disease range from severe abdominal pain to paralysis and respiratory failure.

Alnylam says there are about 5,000 patients in the U.S. and Europe with severe cases of the hepatic porphyria known as acute intermittent porphyria (AIP). There are no drugs available to prevent attacks of the disease from occurring, according to the release.

Alnylam hopes to be the company to change that with ALN-AS1. Last year, researchers using a mouse model found that Alnylam's ALN-AS1 RNAi therapeutic completely blocked the abnormal production of toxic agents of the heme biosynthesis pathway that produces symptoms associated with AIP and the disease's pathology. A single dose of ALN-AS1 had a protective effect that lasted at least two weeks in mice.

- read the release
- learn more about porphyria