Bristol-Myers Squibb Company and Ono Pharmaceutical Co., Ltd. have signed a strategic collaboration agreement to jointly develop and commercialize Opdivo (nivolumab) and Yervoy (ipilimumab) as single agents and combination regimens to help address the unmet medical needs of patients with different types of cancer in Japan, South Korea and Taiwan.
Cancer cells have acquired intelligent strategies to hide from the immune system such as exploiting regulatory pathways like the PD-1 immune checkpoint pathway. PD-1 (programmed death-1) receptor is expressed on activated T cells, and upon binding to one of its ligands it negatively regulates immune responses, decreasing both T cell proliferation and IFN-γ secretion.
Opdivo is an investigational human PD-1 immune checkpoint inhibitor that blocks PD-1, therefore enabling the immune system to recognize, attack and destroy cancer cells. This drug was recently approved in Japan for the treatment of patients with unresectable melanoma and is currently being studied in over 35 clinical trials worldwide as either a monotherapy or in combination with other existing therapies for different cancers, such as non-small cell lung cancer, melanoma, renal cell carcinoma, head and neck cancer, glioblastoma and non-Hodgkin lymphoma. Notably, the FDA granted this experimental drug the Breakthrough Therapy Designation for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab therapy.
Another receptor being investigated as a potential immunotherapy target is CTLA-4 (cytotoxic T- lymphocyte-associated antigen-4), a protein present on the surface of T cells that belongs to the same family as PD-1, and negatively regulates T-cell activation upon binding to its ligands CD80/CD86.
Yervoy, a recombinant human monoclonal antibody, binds to CTLA-4 and blocks the interaction with its ligands, enhancing T-cell activation and proliferation.
In 2011, the FDA approved Yervoy for patients with unresectable or metastatic melanoma. Since then, it has already been approved in more than 40 countries and major development programs for Yervoy spanning multiple tumor types, including Phase 3 trials in prostate and lung cancers, are underway.
The collaboration between Bristol-Myers Squibb and Ono Pharmaceutical ultimately aims to drive forward the development of monotherapies and combination regimens, with Opdivo as the foundational therapy in Japan, South Korea and Taiwan. Additionally, the companies intend to propel global clinical trials that including patients from all three countries.
“Bristol-Myers Squibb’s collaboration with Ono supports our goal to maximize the full potential of our immuno-oncology portfolio for patients worldwide,” said Lamberto Andreotti, chief executive officer, Bristol-Myers Squibb. “This collaboration combines our leadership in immuno-oncology with both companies’ experience and capabilities in Asia, and strengthens our long-standing relationship with Ono.”
The two pharmaceutical companies will jointly develop and commercialize all collaboration products in Japan, South Korea and Taiwan. Prior to this agreement, Ono Pharmaceutical held exclusive rights to develop and commercialize Opdivo in Japan, South Korea and Taiwan while Bristol-Myers Squibb held the same rights in the rest of the world, along with sole rights to develop and commercialize Yervoy worldwide.
“Our collaboration with Bristol-Myers Squibb strengthens our ability to further enhance the potential of Opdivo, for which Ono recently received manufacturing and marketing approval in Japan as the first PD-1 inhibitor approved anywhere in the world,” said Gyo Sagara, President, Representative Director and CEO, Ono Pharmaceutical. “By pursuing the study of investigational combination regimens of immunotherapies with Bristol-Myers Squibb, we hope to bring a range of new therapeutic options to cancer patients.”