Merck & Co. Inc. on Tuesday completed filing its FDA biologics license application for MK-3475 (pembrolizumab), its high-profile programmed cell death 1 (PD-1) inhibitor. The company is seeking approval to treat melanoma patients unsuccessfully treated with Yervoy (ipilimumab, Bristol-Myers Squibb Co.), an indication for which the FDA has granted it both breakthrough designation and priority review status.

The FDA assigned Merck's application an Oct. 28 PDUFA date. If approved, the experimental therapy has the potential to be the first anti-PD-1 antibody in a new class of immune checkpoint modulators, giving it an initial lead on nivolumab, a competing therapy in development by Bristol-Myers Squibb. Merck plans to file a marketing authorization application for MK-3475 in Europe for advanced melanoma by the end of 2014.

"Potent and durable tumor regression" was the headline assessment of anti-PD-1 therapies following data presented at as the 2013 American Society of Clinical Oncology (ASCO) meeting. With this year's ASCO meeting fast-approaching at month's end, the Whitehouse Station, N.J.-based company said it's rolling out 15 company-sponsored abstracts on MK-3475, presenting clinical data from studies in advanced melanoma, advanced non-small-cell lung cancer (NSLCL), as well as advanced head and neck cancer, marking the first time data for MK-3475 will be presented in that cancer type.

About 132,000 people are diagnosed with melanoma each year, and about 756,000 people are reported to be living with the disease. More than 65,000 people lose their lives to the skin cancer annually. But while Merck is targeting melanoma, the most dangerous type of skin cancer, with its first application, that indication is just the tip of the iceberg. The company is developing MK-3475 for use alone and in combination with other drugs for 30 tumor types. By the end of 2014, it expects that 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 III studies.

Analysts are building the rapid expansion of indications into their predictions for MK-3475 sales, with Thomson Reuters Cortellis consensus forecasts suggesting that sales of the therapy could reach $417 million in 2015, then balloon to to $3.1 billion by 2019.

Much work remains to be done. Merck has seven phase III registration trials in the works, including those for advanced melanoma, advanced NSCLC, advanced head and neck cancer and advanced bladder cancer. The company also is pursuing 10 combination studies, including trials for advanced melanoma, advanced NSCLC, advanced renal cell carcinoma, HER2-positive breast cancer and other solid tumors. (See BioWorld Insight, March 3, 2014.)

"Patients with advanced melanoma have few therapeutic options and often fail to respond to all available treatments," said Roger Perlmutter, president of Merck Research Laboratories. "We are hopeful that the FDA, through their priority review of our application, will agree to make MK-3475 available to patients with advanced melanoma who have no other therapeutic options."

TIGHTENING ITS FOCUS

As Merck emphasizes investment in its research-driven business going forward, the company has also looked to realize value built up in its consumer and animal health care businesses. On Tuesday, it off-loaded one, agreeing to sell Merck Consumer Care, one of the world's largest suppliers of over-the-counter products, to Bayer AG for $14.2 billion in cash. Bayer will acquire Merck's existing business, including global trademark and prescription rights for the popular allergy medications Claritin and Afrin.

The acquisition "marks a major milestone on our path towards global leadership in the attractive non-prescription medicines business," said Marijn Dekkers, Bayer's CEO.

Merck also said it has inked a global clinical development collaboration in which Leverkusen, Germany-based Bayer will market and develop its portfolio of soluble guanylate cyclase modulators, including Bayer's Adempas (riociguat), which is approved to treat pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. The two companies will equally share costs and profits from the collaboration, though Merck will pay Bayer $1 billion up front, and additonal sales milestone payments of up to $1.1 billion related to future sales of certain collaboration compounds, including Adempas.