Alnylam Pharma (ALNY) Reports Phase 1 Trial Results Show Proof of Concept for ALN-TTR01

May 10, 2012 7:23 AM EDT
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) announced today final results from its completed Phase I clinical trial with ALN-TTR01, an RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR). The data were presented at the XIII International Symposium on Amyloidosis held May 6-10, 2012 in Groningen, The Netherlands.

Data from this study show that administration of ALN-TTR01 resulted in statistically significant reductions in serum TTR protein levels, including both wild-type and mutant TTR protein, in ATTR patients. Knockdown of TTR, the disease-causing protein, was found to be dose dependent, rapid, and durable after just a single dose. The full time course for TTR knockdown reveals the potential for once monthly or possibly once every other monthly dose regimens in further studies. ALN-TTR was found to be generally safe and well tolerated in this study.

This Phase I study was designed as a randomized, placebo-controlled, single-dose escalation study in patients with ATTR. Patients were enrolled in seven sequential cohorts of increasing doses ranging from 0.01 to 1.0 mg/kg. There were four patients per cohort, with patients randomized to receive drug or placebo in a 3:1 ratio. Following the completion of dose escalation, additional patients were enrolled at 1.0 mg/kg. Data were presented from 32 patients, including eight who received placebo and 24 who received drug.

ALN-TTR01 clinical activity was assessed based on measurements of serum TTR protein levels. ALN-TTR01 demonstrated a dose-dependent reduction in serum TTR levels with a statistically significant mean reduction of 38% at approximately day 7 to 10 in the 1.0 mg/kg group (geometric mean relative to placebo, p=0.01). The rapid onset and durable effect of ALN-TTR01 after a single dose was exemplified by one patient dosed at 1.0 mg/kg who showed 63% TTR lowering at 48 hours, peak TTR knockdown of 81% at day 10, approximately 50% lowering at 30 days post dose, and full recovery only at 60 days. In addition, analysis of serum samples by a liquid chromatography-mass spectrometry method revealed that both mutant and wild-type TTR were knocked down to the same extent in V30M patients; both wild-type and mutant TTR have been shown to cause amyloid plaques in ATTR patients.

ALN-TTR01 was found to be generally safe and well tolerated in ATTR patients. Mild-to-moderate acute infusion reactions were observed in 5 of 24 (20.8%) patients receiving ALN-TTR01 and were readily managed by slowing of the infusion rate where necessary. There were no significant increases in liver function test parameters. All patients on study drug completed the study; there were no discontinuations except for one patient in the placebo group who underwent elective hospitalization for a liver transplant, and was scored as a serious adverse event unrelated to study drug.

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