Bristol-Myers Squibb Company (BMS) and Ono Pharmaceutical Co, an R&D-oriented pharmaceutical company, have signed a strategic collaboration agreement to jointly develop and commercialise multiple immunotherapies as single agents and combination regimens to help address the unmet medical needs of patients with cancer in Japan, South Korea and Taiwan.
As part of the agreement, Bristol-Myers Squibb and Ono will jointly develop and commercialise Opdivo (nivolumab) and Yervoy (ipilimumab) across a broad range of tumour types.
Opdivo is a PD-1 immune checkpoint inhibitor approved in Japan for the treatment of patients with unresectable melanoma, making it the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world, and is being developed in multiple tumour types in more than 35 clinical trials. Yervoy, a CTLA-4 immune checkpoint inhibitor, is approved in Taiwan for the treatment of patients with advanced melanoma who have received prior therapy, and is in late-stage development as a potential treatment option for melanoma, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) in Japan. The agreement includes three additional early-stage clinical immuno-oncology assets from Bristol-Myers Squibb: lirilumab, an antibody that blocks the KIR receptor on natural killer cells, urelumab, an agonist of the CD137 co-stimulatory receptor, and BMS-986016, a LAG3 immune checkpoint inhibitor.
Bristol-Myers Squibb and Ono will jointly pursue development of monotherapy and combination regimens, with Opdivo as the foundational therapy in Japan, South Korea and Taiwan, and leverage global clinical trials by including patients from the three countries.
“Bristol-Myers Squibb’s collaboration with Ono supports our goal to maximise 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.”
“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 chief executive officer, Ono. “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.”
Under the terms of the agreement, Bristol-Myers Squibb and Ono will jointly develop and commercialise all collaboration products in Japan, South Korea and Taiwan. Development costs and commercial profits will be shared equally when Opdivo is used in combination with any Bristol-Myers Squibb compound (Yervoy, lirilumab, urelumab, BMS-986016). For a Bristol-Myers Squibb compound used as monotherapy, or two Bristol-Myers Squibb compounds used in a combination regimen, Bristol-Myers Squibb will fund the substantial majority of development costs and receive the substantial majority of commercial profits. When Opdivo is used as a single agent, Ono will fund the substantial majority of development costs and receive the substantial majority of commercial profits.
Prior to this announcement, Ono held exclusive rights to develop and commercialise Opdivo in Japan, South Korea and Taiwan while Bristol-Myers Squibb held such rights in the rest of the world, along with sole rights to develop and commercialize Yervoy, lirilumab, urelumab, and BMS-986016 worldwide. The trade name Opdivo has been proposed in the US and other countries, but remains subject to health authority approval.
Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumour from immune attack. Opdivo is an investigational human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programme death-1) expressed on activated T-cells. The companies are investigating whether by blocking this pathway, Opdivo would enable the immune system to resume its ability to recognise, attack and destroy cancer cells.
Opdivo was approved in Japan on July 4, 2014 for the treatment of patients with unresectable melanoma and is being studied in multiple tumour types in more than 35 trials as monotherapy or in combination with other therapies in which more than 7,000 patients have been enrolled worldwide. Among these are several potentially registrational trials in NSCLC, melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma and non-Hodgkin lymphoma. In 2013, the FDA granted Fast Track designation for Opdivo in NSCLC, melanoma and RCC. In May 2014, the FDA granted Opdivo Breakthrough Therapy Designation for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab.
Yervoy, which is a recombinant, human monoclonal antibody, blocks the cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of Yervoy’s effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumour immune responses. On March 25, 2011, the FDA approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is now approved in more than 40 countries, including Taiwan. There is a broad, ongoing development programme in place for Yervoy spanning multiple tumour types. This includes Phase 3 trials in prostate and lung cancers.