Bristol-Myers Squibb Company, a global pharmaceutical company, announced that the European Medicines Agency (EMA) has validated two of the company’s type II variation applications, which seek to extend the current indication for its immuno-oncology agent, Opdivo. Validation of the applications confirms that the submissions are complete and starts the EMA's centralised review process.

In lung cancer, the proposed new indication addresses the non-squamous non-small cell lung cancer (NSCLC) population -- Opdivo as monotherapy for the treatment of locally advanced or metastatic non-squamous NSCLC after prior chemotherapy in adults. In melanoma, the proposed new indication aims to extend the use of Opdivo monotherapy to its use in combination -- Opdivo in combination with Yervoy for the treatment of advanced (unresectable or metastatic) melanoma in adults.

“The starting of the EMA’s centralised review process marks a significant milestone in our commitment to make Opdivo available for a broader range of appropriate patients with advanced melanoma and lung cancer in Europe,” said Michael Giordano, M.D., senior vice president, head of oncology development, Bristol-Myers Squibb. “Today’s announcement also is a step forward in realising our vision to change survival expectations, transform the standard of cancer care, and the way patients live with cancer across multiple tumour types. We look forward to working with the EMA during its review process.”

The type II variation submitted to the EMA in non-squamous NSCLC is supported by data from the landmark, global phase 3 study, CheckMate -057, which evaluated the survival of patients with advanced non-squamous NSCLC who had progressed during or after one prior platinum doublet-based chemotherapy regimen. The type II variation application in advanced melanoma is based on data from two studies: CheckMate -067, a pivotal phase 3 study that evaluated the Opdivo+Yervoy regimen or Opdivo monotherapy vs. Yervoy monotherapy in adults with previously-untreated advanced melanoma, and the phase 2 CheckMate -069, the first randomized trial evaluating the Opdivo+Yervoy regimen in patients with previously-untreated advanced melanoma, as well as supportive data from the phase 1b CA209004 study in advanced melanoma.

Bristol-Myers Squibb submitted two separate Marketing Authorisation Applications (MAA), one in advanced melanoma under the tradename Opdivo and one for squamous NSCLC under the tradename Nivolumab BMS in order to accelerate availability of nivolumab for health care professionals in both indications. The EMA has accepted Bristol-Myers Squibb’s application to “reconcile” the MAAs into a single marketing authorisation under the tradename Opdivo. The goal is to have the MAAs reconciled toward the end 2015.

Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumour from immune attack. Opdivo and Yervoy are both monoclonal antibodies and immune checkpoint inhibitors that target separate, distinct checkpoint pathways. Inhibition of these immune checkpoint pathways results in enhanced T-cell function greater than the effects of either antibody alone.

Opdivo became the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world on July 4, 2014 when Ono Pharmaceutical Co. announced that it received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma. In the US, the Food and Drug Administration (FDA) granted its first approval for Opdivo for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy and, if BRAF V600 mutation positive, a BRAF inhibitor. On March 4, 2015, Opdivo received its second FDA approval for the treatment of patients with advanced squamous NSCLC with progression on or after platinum-based chemotherapy. The European Commission (EC) announced approval of Opdivo on June 19, 2015, for the treatment of advanced (unresectable or metastatic) melanoma in adults, regardless of BRAF status, and on June 20, 2015, the EC announced it approved Nivolumab BMS for the treatment of locally advanced or metastatic squamous NSCLC after prior chemotherapy.

On March 25, 2011, the FDA approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. In July 2011, approval of Yervoy was granted in Europe by the European Commission for the treatment of advanced melanoma patients after prior treatment; the Marketing Authorization was extended in May 2013 to the untreated advanced melanoma population. Yervoy is now approved in more than 40 countries.

Bristol-Myers Squibb has a broad, global development programme with over 8,000 patients enrolled in more than 50 trials evaluating nivolumab across multiple tumour types – as monotherapy or in combination with other therapies.