July 30, 2018
GSK’s ViiV Healthcare presented results from the Phase III GEMINI 1 & 2 studies, assessing the safety and efficacy of a two-drug regimen (2DR) of dolutegravir (DTG) and lamivudine (3TC) compared to a three-drug regimen of dolutegravir and two nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), in treatment-naïve, HIV-1 infected adults. The studies are designed to demonstrate the non-inferior efficacy, safety and tolerability of once-daily dolutegravir and lamivudine compared to once-daily dolutegravir and the fixed-dose combination of TDF/FDC. GEMINI 1 (204861) and GEMINI 2 (205543) are duplicate, Phase III, randomized, double-blind, multicenter, parallel group, non-inferiority studies. These studies enrolled naïve adult participants with baseline HIV-1 viral loads up to 500,000 copies per ml. The studies met their primary endpoint for non-inferiority based on plasma HIV-1 RNA <50c/mL, a standard measure of HIV control, at Week 48. Results show broadly consistent results for virus suppression across individuals with higher viral load. Pooled results show that the most common (≥5 percent) adverse events across the studies were headache, diarrhea and nasopharyngitis in both arms (DTG + 3TC arm: 10 percent, 9 percent, and 8 percent, respectively, DTG + TDF/FTC: 10 percent, 11 percent, and 11 percent). Rates of virologic failure were ≤1 percent across all arms of the study. Drug-related adverse events were less frequent in patients on the DTG/3TC regimen (126/716, 18 percent), compared with those on the DTG + TDF/FTC regimen (169/717, 24 percent).
Aldeyra Therapeutics Enrolls First Sjögren-Larsson Syndrome Patient in Phase III Clinical Trial
Aldeyra Therapeutics announced that the first patient has enrolled in a pivotal Phase III clinical trial of topical dermal reproxalap for the treatment of ichthyosis (scaly, thickened, dry skin) associated with Sjögren-Larsson Syndrome (SLS). The randomized, double-blind, multi-center, parallel-group Phase III clinical trial is expected to be performed in two parts: the first part of the trial will assess six months of treatment in select areas of ichthyosis over increasing proportions of body surface area; the second part of the trial is expected to assess six months of treatment in all areas of ichthyosis. Data generated from the first part of the trial will be used to confirm statistical power for the second part of the trial. The primary endpoint for the second part of the trial will be improvement in ichthyosis in drug-treated patients over six months of therapy.
Aura Biosciences: Interim Phase Ib/II data for Choroidal Melanoma Therapy
Aura Biosciences presented interim data from an open-label Phase Ib/II study of its lead program, light-activated AU-011 for the treatment of primary choroidal melanoma. Interim data show that in an expanded set of subjects AU-011 continues to be well-tolerated with no related serious adverse events, no severe adverse events and no dose-limiting toxicities observed, including the cohorts in the multiple ascending dose phase of the study. Adverse events were manageable with standard-of-care treatments and there have been no long-term clinical sequelae. Pre-treatment visual acuity was maintained in all subjects that have been followed for six to 12 months. The Phase Ib/II open-label, multicenter trial has been designed to evaluate the safety and efficacy of single and multiple ascending doses in 30 adult subjects with clinically diagnosed small to medium primary choroidal melanoma. Early efficacy results continue to be promising, with several subjects in the multiple-ascending-dose cohorts showing evidence of reduction in tumor height and 100 percent of the patients meeting the endpoint of stable disease at three months.
Alnylam: New Analyses of APOLLO Phase III Trial Results
Alnylam Pharmaceuticals announced new analyses from the APOLLO Phase III study of patisiran, an investigational RNAi therapeutic for the treatment of hereditary ATTR (hATTR) amyloidosis. The trial enrolled 225 hATTR amyloidosis patients in 19 countries with 39 genotypes who were randomized 2:1, patisiran:placebo, with patisiran administered at 0.3 mg/kg intravenously once every three weeks for 18 months. 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 Neuropathy Impairment Score +7 (mNIS+7) relative to placebo at 18 months. The primary endpoint in APOLLO was the change from baseline in the modified Neuropathy Impairment Score + 7 (mNIS+7) relative to placebo, with patisiran demonstrating significant improvement in neuropathy. Patisiran was generally well tolerated, and the common adverse events (AEs) occurring more frequently with patisiran than placebo were peripheral edema (29.7 versus 22.1 percent) and infusion-related reactions (IRRs; 18.9 versus 9.1 percent). Predicative modeling showed that patients with an mNIS+7 change of less than zero points after 18 months of patisiran treatment were predicted to have substantially greater odds of improving or stabilizing their ambulatory status compared to patients with an mNIS+7 score of greater than or equal to zero (p value less than 0.0001). It was shown that following 18 months of treatment, a greater proportion of patisiran patients compared to placebo showed stable or improved FAP Stage (79 versus 44 percent) and PND score (73 versus 30 percent).