Pipeline Previews

Merck has announced that the FDA has accepted for review the Biologics License Application (BLA) for MK-3475, Merck’s investigational anti-PD-1 antibody, for the treatment of unresectable or metastatic melanoma in patients who have been previously treated with ipilimumab. The FDA granted Priority Review designation with a PDUFA date of October 28, 2014, and the MK-3475 BLA will be reviewed under the FDA’s Accelerated Approval program. The FDA previously granted MK-3475 Breakthrough Therapy designation for advanced melanoma, the most dangerous type of skin cancer. If approved by the FDA, MK-3475 has the potential to be the first anti-PD-1 antibody in a new class of immune checkpoint modulators. Merck also announced it plans to file a Marketing Authorization Application for MK-3475 in Europe for advanced melanoma by the end of 2014.

The MK-3475 development program is currently ongoing in 30 tumor types as monotherapy and in combination. Merck anticipates that by the end of 2014, the MK-3475 development program will grow to more than 24 clinical trials across 30 different tumor types, enrolling an estimated 6,000 patients at nearly 300 clinical trial sites worldwide, including four new Phase 3 studies. Ongoing and planned late-stage monotherapy and combination studies include seven Phase 3 registrational trials spanning advanced melanoma (adjuvant, ipilimumab-naïve, and ipilimumab-refractory), advanced non-small cell lung cancer (NSCLC) (previously-treated and previously-untreated), advanced head & neck cancer and advanced bladder cancer; and, ten combination studies, including advanced melanoma, advanced NSCLC, advanced renal cell carcinoma, HER2+ breast cancer and other solid tumors.

Merck has also reported that based on encouraging preclinical data, it plans to initiate a Phase 1 dose-ranging study with its investigational anti-GITR agonistic antibody, MK-4166, in patients with advanced malignances. GITR (glucocorticoid-induced TNFR receptor) is an activating immune checkpoint receptor, which is believed to stimulate immune activity against cancer cells. This will be the second investigational immune checkpoint antibody within Merck’s immuno-oncology discovery program to enter clinical development.

GlaxoSmithKline has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending marketing authorization for Mekinistâ„¢ (trametinib) as a single agent in the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation. Trametinib as a single agent has not demonstrated clinical activity in patients who have progressed on a prior BRAF inhibitor therapy. Before taking trametinib, patients must have confirmation of BRAF V600 mutation using a validated test.

The CHMP recommendation for trametinib monotherapy is based on a randomized open label phase III study comparing trametinib to chemotherapy in 322 patients with BRAF mutant melanoma (V600E and V600K) and a non-randomized phase II study in 97 patients with BRAF mutant melanoma split in two cohorts: previously treated or not treated with a BRAF inhibitor.

A CHMP positive opinion is one of the final steps before marketing authorization is granted by the European Commission (EC), but does not always result in marketing authorization. A final decision by the EC is anticipated during the second quarter of 2014.

Novartis has announced results from the Phase III FEATURE and JUNCTURE studies showing secukinumab (AIN457), a selective interleukin-17A (IL-17A) inhibitor, met both co-primary endpoints at Week 12 based on Psoriasis Area and Severity Index (PASI) 75 and Investigator's Global Assessment modified 2011 (IGA mod 2011) 0/1 response rates compared to placebo. Results from these studies also demonstrated skin clearance at Week 12 based on PASI 90 response rates compared to placebo, usability and acceptability of the secukinumab pre-filled syringe (PFS) and autoinjector pen (AI), and an approximately 50% mean decrease in PASI scores from baseline by Week 3 (300mg) and Week 4 (150mg). These results, along with more than 20 posters were presented for the first time at the 72^nd Annual Meeting of the American Academy of Dermatology (AAD) in Denver.

FEATURE results showed the efficacy of secukinumab 300mg and 150mg based on a statistically significant higher proportion of patients who achieved a PASI 75 response at Week 12 compared with placebo patients: 75.9% (300mg) and 69.5% (150mg), versus 0% for placebo (p <.0001). On the co-primary endpoint, the efficacy of secukinumab 300mg and 150mg was shown based on a statistically significant higher proportion of patients who achieved an IGA mod 2011 0/1 response at Week 12 compared with placebo: 69.0% (300mg) and 52.5% (150mg), versus 0% for placebo (p <.0001).