Pipeline Previews

risk; pediatric patients in the prevention of CMV disease in kidney or heart transplant patients at high risk.

Roche’s Valcyte is also available as an oral solution (50 mg/mL).

Hovione has announced that it has filed an Investigational New Drug (IND) Application with the FDA for minocycline gel, a novel formulation to administer topically using a new patented crystalline base form of minocycline, one of the most widely prescribed oral antibiotics for acne. Pending FDA’s acceptance of the IND submission, Hovione plans to initiate human clinical Phase 1/2 studies in early 2015.

Bristol-Myers Squibb Company has announced that the FDA approved Opdivo (nivolumab) injection, for intravenous use. Opdivo is a human programmed death receptor-1 (PD- 1) blocking antibody indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Opdivo demonstrated efficacy in a Phase 3, pivotal clinical trial with advanced melanoma in patients who had been previously treated and progressed with Yervoy and, if BRAF mutation positive, a BRAF inhibitor. The efficacy of Opdivo was evaluated based on a single-arm, non-comparative planned interim analysis of the first 120 patients who received Opdivo with a minimum of 6 months follow-up in the Phase 3 CheckMate -037 trial.

Opdivo achieved a 32% (95% CI: 23, 41) response rate (38/120) with a dosing strength and frequency of 3 mg/kg intravenously over 60 minutes every 2 weeks. 3% of patients (4/120) achieved a complete response, and 28% (34/120) achieved a partial response. Of 38 patients with responses, 33 patients (87%) had ongoing responses with durability of response ranging from 2.6+ to 10+ months, which included 13 patients with ongoing responses of 6 months or longer. Responses to Opdivo were demonstrated in both patients with and without BRAF mutation.

The safety profile of Opdivo has been demonstrated in the pivotal, Phase 3 CheckMate-037 trial. Serious adverse reactions occurred in 41% of patients receiving Opdivo. Grade 3 and 4 adverse reactions occurred in 42% of patients receiving Opdivo. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving Opdivo were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. The most common adverse reaction (≥20%) reported with Opdivo was rash (21%).

CheckMate -037 was a randomized, Phase 3 trial evaluating Opdivo 3 mg/kg (n=268), administered every two weeks, or chemotherapy (n=102) (investigator's choice of either single-agent dacarbazine 1000 mg/m2 every 3 weeks or the combination of carboplatin AUC 6 every 3 weeks plus paclitaxel 175 mg/m2 every 3 weeks) in patients with advanced melanoma who had been previously treated and progressed with Yervoy and, if BRAF mutation positive, a BRAF inhibitor. No premedication is required with Opdivo.

The primary objective of this analysis of the CheckMate -037 trial was Objective Response Rate (ORR). CheckMate -037 included 90 participating trial sites in 14 countries, and included both institutional and community practice centers. The clinical study is ongoing to determine whether there is an overall survival benefit.

In the Opdivo treated patients (n=120), 76% of patients had M1C disease, 18% of patients had a history of brain metastases, and 56% of patients had elevated LDH levels. The median age of patients was 58. 22% of patients were BRAF V600 mutation positive.