Although it has been predicted that this will be a lean year for the approval and launch of blockbuster drugs this picture could all change if any of the anti-programmed death-1 (PD-1) antibodies under development make it to market.

In this space investors will certainly be keeping a close watch on Merck & Co. Inc., which announced in January its rolling FDA submission of a biologics license application for MK-3475, an anti-PD-1 immunotherapy, for patients with advanced melanoma who are refractory to the immunotherapy Yervoy (ipilimumab, BMS), the first immunotherapy to win FDA clearance. That submission is expected to finish in the first half of this year. (See BioWorld Today, Jan. 15, 2014.)

There is no doubt that agents that target the PD-1 pathway have generated much excitement among investors. Merck’s PD-1 therapy is high on its priority list. The company is being closely scrutinized on the strategic and operating actions it is taking to drive short- and long-term growth, and the news on MK-3475 was welcomed by analysts who cover the company.

“As we consider the landscape in immuno-oncology (IO), we believe Merck is carefully carving out a strong position for PD1 monotherapy broadly in melanoma and it will be a staunch competitor in PDL1 + lung cancer patients (approximately 20 percent to 30 percent of lung cancer patients). In addition, efforts to carve out a place as backbone therapy in IO combinations is strategically sound in this fast-moving area, in our view,” noted Leerink Swann analyst Seamus Fernandez in a research report.

MULTIPLE TRIALS

The product is now in 10 trials in more than 10 cancers, including a collaboration with Glaxosmithkline plc, of London, to evaluate MK-3475 in combination with GSK’s oral kinase inhibitor, pazopanib, in advanced renal cell carcinoma. The companies began a phase I/II trial evaluating safety and efficacy of the compound in treatment-naïve patients with the disease.

Merck also announced in February that it had entered into three separate deals that would bring MK-3475 into various phase I/II trials with cancer drugs from Amgen Inc., Incyte Corp. and Pfizer Inc. – transactions intended to help the company keep pace with the likes of Bristol-Myers Squibb Co. (BMS) in the anti-PD-1 space by getting access to unpartnered cancer assets by way of research pacts. (See BioWorld Today, Feb. 6, 2014.)

With Amgen, of Thousand Oaks, Calif., the oncolytic immunotherapy talimogene laherparepvec will be tested with MK-3475 in patients with previously untreated advanced melanoma.

Merck will be testing MK-3475 with Incyte’s immunotherapy agent, INCB24360, an indoleamine 2,3-dioxygenase inhibitor, often referred to as IDO, in patients with previously treated metastatic and recurrent non-small-cell lung cancer, among other advanced or metastatic cancers.

Pfizer, of New York, has two drugs to enter experiments: the small molecule kinase inhibitor Inlyta (axitinib) – approved about a year ago for renal cell carcinoma (RCC) – to be tried with the Merck therapy in patients with RCC, and PF-05082566 (PF-2566), described as an immuno-oncology drug that targets the 4-1BB receptor, which will be explored in multiple cancer types.

GAINING A FOOTHOLD

In August last year Astrazeneca plc revealed that MedImmune, its global biologics research and development arm, was acquiring Amplimmune Inc., a company focused on developing therapeutics in cancer immunology for $225M up front and another $275 million in potential milestone payments.

The acquisition certainly bolsters Medimmune’s oncology pipeline by obtaining multiple early stage assets for its immune-mediated cancer therapy (IMT-C) portfolio, including AMP-514, an anti-programmed cell death 1 (PD-1) monoclonal antibody (MAb). AMP-514 is currently in late-stage preclinical development with the aim of an investigational new drug (IND) filing. (See BioWorld Today, Aug. 27, 2013.)

Although no financial terms were revealed, Novartis AG, further established its “stake in the PD-1 space” and broadened its interest in cancer immunotherapy research through the acquisition of Costim Pharmaceuticals Inc., a Cambridge, Mass.-based, privately held biotechnology company.

The acquisition, the company explained, adds late discovery stage immunotherapy programs directed to several targets, including PD-1.

Basel, Switzerland-based Roche AG has an anti-PD-1 program, too. Last September the company presented data from an updated analysis of a phase I study assessing MPDL3280A monotherapy in patients with advanced or metastatic non-small-cell lung cancer (NSCLC) showed that MPDL3280A was generally well tolerated and yielded often rapid, durable responses. Response rates were particularly high in patients who had greater expression of PD-L1 in their tumors as measured by a Roche tissue diagnostics immunohistochemistry (IHC) assay.

Roche said it has initiated two phase II studies of MPDL3280A in patients with NSCLC, and pivotal studies are planned.

Editor’s note: The second part of this article will appear in next week’s issue.