ALN-VSP / Alnylam, Ascletis - LARVOL DELTA

Dual-targeted approaches in cancer therapy: integrating siRNA and chemotherapy for improved outcomes. (PubMed, 3 Biotech) - "Early clinical candidates, such as EZN-3042 and ALN-VSP, achieved target engagement and biological activity, while limitations included variable tumour uptake, dose-limiting toxicities, and complex pharmacokinetic behaviour. Translation to clinical practice will depend on optimised delivery platforms, reproducible pharmacokinetic/pharmacodynamic synchronisation, and rigorous evaluation of safety and off-target effects. Overall, current evidence highlights substantial potential for siRNA-drug co-delivery while emphasizing key challenges to overcome in achieving durable clinically meaningful outcomes."

Journal • Review • Oncology • BCL2 • BIRC5 • EGFR • HER-2 • MET • MUC1

Advances in Antibody-Based Therapeutics for Cerebral Ischemia. (PubMed, Pharmaceutics) - "Recently, Clone MTS510 antibody targeting toll-like receptor-4 (TLR4) protein, ASC06-IgG1 antibody targeting acid sensing ion channel-1a (ASIC1a) protein, Anti-GluN1 antibodies targeting N-methyl-D-aspartate (NMDA) receptor associated calcium influx, GSK249320 antibody targeting myelin-associated glycoprotein (MAG), anti-High Mobility Group Box-1 antibody targeting high mobility group box-1 (HMGB1) are currently under clinical trials for cerebral ischemia treatment. In this article, we review the current antibody-based pharmaceuticals for neurological diseases, the use of antibody drugs in stroke, strategies to improve the efficacy of antibody therapeutics in cerebral ischemia, and the recent advancement of antibody drugs in clinical practice. Overall, we highlight the need of enhancing blood-brain barrier (BBB) penetration for the improvement of antibody-based therapeutics in the brain, which could greatly enhance the antibody medications for cerebral ischemia in..."

Journal • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • HMGB1 • TLR4

Alnylam presents phase I data for ALN-VSP, an RNAi therapeutic for the treatment of liver cancers, at American Society of Clinical Oncology (ASCO) meeting (Alnylam) - P1, N=41; 50% (12 of 24) of pts evaluable for response attained SD or better with ALN-VSP doses ≥0.7 mg/kg, compared to only 8% (1 of 13) at doses ≤0.4 mg/kg; 64% (7 of 11) of pts achieved SD at the recommended P2 dose of 1.0 mg/kg & 45% (5 of 11) continue to receive drug on study; In addition, DCE-MRI results were suggestive of an anti-VEGF effect

P1 data presentation • Hepatocellular Cancer • None • Oncology

Open-label extension study of the RNAi therapeutic ALN-VSP02 in cancer patients responding to therapy (ASCO 2012) - Presentation time: Monday June 4, 8:00 AM to 12:00 PM; P1, N=37; Study ID: ALN-VSP02-002; At the time of enrollment, 6 had SD & one (endometrial cancer with multiple liver metastases) had an unconfirmed PR; 3 pts remain on study, including the endometrial cancer pt with an ongoing PR who has had >80% tumor regression after 19 months of treatment at 0.7 mg/kg & two pts with RCC & PNET with continued SD after nearly 1 yr of treatment at 1.0 mg/kg

P1 data • Oncology • Pancreatic Cancer • Renal Cell Carcinoma

Alnylam Pharmaceuticals reports fourth quarter and full year 2011 financial results (Alnylam) - Alnylam intends to partner ALN-VSP prior to initiating a P2 study

Anticipated partnership • Oncology

Alnylam completes enrollment in ALN-VSP phase I clinical trial (Businesswire) -

P1, N=40; Alnylam completed enrollment in its ALN-VSP P1 trial; Study’s objectives were to evaluate safety, tolerability, PK, & PD in pts with adv solid tumors with liver involvement;

Oncology