Trial Results

Alnylam Reports Results from the APOLLO Phase III Study

April 30, 2018

Alnylam Pharmaceuticals announced new results from the APOLLO Phase III study of patisiran, an investigational RNAi therapeutic for the treatment of hereditary ATTR (hATTR) amyloidosis. The APOLLO Phase III trial was a randomized, double-blind, placebo-controlled, global study designed to evaluate the efficacy and safety of patisiran in hATTR amyloidosis patients with polyneuropathy. The primary endpoint of the study was the change from baseline in modified Neurologic Impairment Score +7 (mNIS+7) relative to placebo at 18 months. The trial enrolled 225 hATTR amyloidosis patients from 19 countries with 39 genotypes who were randomized 2:1, patisiran:placebo, with patisiran administered at 0.3 mg/kg once every three weeks for 18 months. There were 13 deaths in the APOLLO study; none were considered related to study drug and the frequency of deaths was lower in the patisiran group (4.7 percent) as compared with placebo (7.8 percent). While treatment benefit is observed across all stages of disease, these results support the rationale for early treatment with patisiran to potentially halt or improve neuropathy progression or impairment, respectively.

Paratek Pharmaceuticals Presents Data for Skin Infections Trial
Paratek Pharmaceuticals announced that an analysis of microbiology data from OASIS-2, its second Phase III study of omadacycline in acute skin infections, found that once-daily monotherapy with oral omadacycline is effective in treating frequently isolated pathogens associated with skin infections. The OASIS-2 study was a randomized, double-blind, multi-center study that enrolled 735 adult subjects with moderate to severe ABSSSI at 33 centers in the U.S. Patients received either once-daily, oral omadacycline or twice-daily, oral linezolid for 7 to 14 days. To analyze clinical success per infection type in OASIS-2, the modified intent-to-treat (mITT) population included randomized subjects without a sole Gram-negative pathogen(s) at baseline (n=720). Infection type broke down as follows: 59 percent wound infection; 24 percent cellulitis/erysipelas and 18 percent major abscess. In the pivotal Phase III OASIS-2 study, omadacycline met the FDA-specified primary endpoint of statistical non-inferiority (NI) in the modified intent-to-treat (mITT) population (10 percent NI margin, 95 percent confidence interval) compared to linezolid at the early clinical response (ECR), 48 to 72 hours after the first dose of study drug.

Tarveda Therapeutics Doses First Patient in Phase I/IIa Study
Tarveda Therapeutics announced that it has dosed the first patient in a Phase I/IIa study evaluating PEN-866 in patients with advanced solid tumors. PEN-866 is a miniature drug conjugate that selectively binds to the intracellular target Heat Shock Protein 90 (HSP90) and is linked to SN-38, a known and potent anti-cancer payload. The multi-center, dose escalation and expansion study will assess safety and efficacy across a range of tumor types including those previously shown to be sensitive to topoisomerase 1 inhibitors. This includes but is not limited to small cell lung, pancreatic, triple negative breast, colon and ovarian cancers and sarcomas. The Phase IIa portion of the trial has now been initiated and enrollment has begun in patients with small cell lung cancer as well as GI-midgut and pancreatic neuroendocrine tumors that express SSTR2. PEN-866 is a miniature conjugate that comprises a small molecule, HSP90-targeting ligand linked to SN-38, the active metabolite of irinotecan. Checkmate Pharmaceuticals Announces Start of Phase Ib Trial
Checkmate Pharmaceuticals announced that it had initiated treatment with CMP-001 combined with atezolizumab (TECENTRIQ) in a Phase Ib clinical trial of patients with advanced non-small cell lung cancer (NSCLC) and disease progression on prior anti-PD-1/PD-L1 therapy. CMP-001 is designed to activate innate immunity to convert “uninflamed” tumors, which generally do not respond to anti-PD-1/L1 therapy, into “inflamed” tumors, which are responsive to PD-1 inhibition. The trial is designed as a multi-center, open label, two-part Phase 1b study of CMP-001 administered in combination with atezolizumab with and without low-level radiation therapy. Part one of the study will evaluate CMP-001 (5 mg dose) administered subcutaneously (SC) weekly for two weeks and then intratumorally (IT) weekly for three weeks, followed by either SC or IT injection every three weeks. In the second part of the trial, the combination of CMP-001 and atezolizumab therapy will be preceded by low-level radiation therapy to the target lesion.