Capella

Capella—the Online Voice of Progress in RNAi

Alnylam welcomes you to Capella, the destination for updates on our progress in translating the science of RNAi into innovative medicines. For Alnylam, Capella is our online voice for communicating the scientific progress we are making as we work to develop innovative medicines for patients.

We presented new pre-clinical data with ALN-HBV, an investigational RNAi therapeutic targeting the Hepatitis B Virus (HBV) genome for the treatment of HBV infection. The ALN-HBV siRNA targets a highly conserved site across genotypes A-J, mapping to the X open reading frame, which is downstream from the most prevalent integration hotspot targeted by siRNAs from other developers. ALN-HBV is thus expected to achieve potent knockdown of HBV surface antigen (HBsAg) expressed by both covalently closed circular DNA (cccDNA) and integrated HBV DNA. Pre-clinical study results in rodent HBV models showed that subcutaneous administration of ALN-HBV led to potent and durable knockdown of HBsAg. Single doses of ALN-HBV in mice resulted in an up to 3.6 log10 and a mean of 1.6 log10 reduction of HBsAg 15 days after a single dose. Further, multiple doses of ALN-HBV in rats showed highly durable knockdown, with effects lasting up to 4 months following three weekly doses of ALN-HBV at 3 mg/kg. In addition, ALN-HBV was generally well tolerated in all rodent models.


 

(more…)

Alnylam and The Medicines Company reported updated positive results from the ongoing Phase 1 clinical trial with ALN-PCSsc, an investigational RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia.  We had previously reported that subcutaneous administration of ALN-PCSsc resulted in an up to 83 percent lowering of LDL-C, with an up to 64 ± 5 percent mean maximum reduction. In new results, the effects of ALN-PCSsc were also found to be highly durable, with clinically significant and clamped reductions in LDL-C that now confirm the potential for a bi-annual subcutaneous dose regimen. An up to 53 percent maximal and 47 percent least squares mean reduction in LDL-C was achieved at day 180 after a single, low volume injection. In addition, ALN-PCSsc was shown to reduce a number of atherogenic lipids, including lipoprotein (a), and total cholesterol, which are associated with increased risk of cardiovascular disease. Importantly, ALN-PCSsc was generally well tolerated with no clinically significant drug-related adverse events to date.



(more…)

We reported data from our ongoing Phase 2 open-label extension (OLE) studies with patisiran and revusiran, investigational RNAi therapeutics targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR amyloidosis).






(more…)

We presented pre-clinical data with ALN-TTRsc02, an investigational RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR amyloidosis).  In pre-clinical studies, including those in non-human primates (NHPs), ALN-TTRsc02 achieved potent and highly durable knockdown of serum TTR of up to 99% with multi-month durability achieved after just a single dose, supportive of a potentially once quarterly dose regimen. Results from studies comparing TTR knockdown activity of ALN-TTRsc02 to that of revusiran showed that ALN-TTRsc02 has a markedly superior TTR knockdown profile.  Further, in initial rat toxicology studies, ALN-TTRsc02 was found to be generally well tolerated with no significant adverse events at doses as high as 100 mg/kg.



(more…)

We announced advancement of innovations in RNAi therapeutics with presentation of scientific data on two new platform technologies: Bis-RNAiTM and ReversirTM.  The Bis-RNAi platform enables simultaneous knockdown of two distinct disease genes using a single, subcutaneously administered molecular entity consisting of two linked siRNAs conjugated to a GalNAc moiety. The Reversir platform enables tailored control of RNAi pharmacology with rapid reversal of target gene silencing effects using GalNAc-conjugated, single-stranded oligonucleotide constructs that are designed to recognize and bind to the complimentary RISC-bound antisense strand of an siRNA.




(more…)

We reported data from our ongoing Phase 2 open-label extension (OLE) study of patisiran, an investigational RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR amyloidosis) patients with familial amyloidotic polyneuropathy (FAP). Alnylam scientists and collaborators from The Scripps Research Institute and Misfolding Diagnostics, Inc. were able to measure the effects of patisiran on pathogenic, misfolded TTR monomers and oligomers in FAP patients. Results showed a rapid and sustained reduction in serum non-native conformations of TTR (NNTTR) of approximately 90%. Since NNTTR is pathogenic in ATTR amyloidosis and the level of NNTTR reduction correlated with total TTR knockdown, these results provide direct mechanistic evidence supporting the therapeutic hypothesis that TTR knockdown has the potential to result in clinical benefit. Furthermore, complete 12-month data from all 27 patients that enrolled in the patisiran Phase 2 OLE study showed sustained mean maximum reductions in total serum TTR of 91% for over 18 months and a mean 3.1-point decrease in mNIS+7 at 12 months, which compares favorably to an estimated increase in mNIS+7 of 13 to 18 points at 12 months based upon analysis of historical data sets in untreated FAP patients with similar baseline characteristics. Importantly, patisiran administration continues to be generally well tolerated out to 21 months of treatment.




(more…)

We hosted a series of online “RNAi Roundtables” in July, August and September, at which Alnylam scientists and key clinical collaborators reviewed recent progress in many of the company’s development-stage pipeline programs and discussed the related disease areas.

Click on any of the RNAi Roundtables below to listen to the webcasts and view presentations from these events. (more…)

We reported positive initial results from our ongoing Phase 1 clinical trial with ALN-AS1, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias. Study results showed that single subcutaneous doses of ALN-AS1 resulted in an up to 82% lowering of ALA and an up to 93% lowering of PBG in asymptomatic “high excreter” (ASHE) patients, who carry the genetic mutation of acute intermittent porphyria (AIP) and have elevated levels of aminolevulinic acid (ALA) and porphobilinogen (PBG), the toxic heme intermediates that mediate porphyria attacks. Furthermore, analysis of exosomal mRNA preparations from serum and urine revealed that treatment resulted in potent, dose-dependent, and durable silencing of liver ALAS1 mRNA.  Importantly, ALN-AS1 was found to be generally well tolerated with no clinically significant drug-related adverse events to date. These data provide human proof-of-concept for ALN-AS1 as a potential therapy for AIP and other acute hepatic porphyrias.



(more…)

SIGN UP FOR EMAIL UPDATES

Receive news and updates on the work at Alnylam that affects you most.