Opdivo first PD-1 treatment to gain European approval

Bristol-Myers Squibb (BMS) has scored a victory over its rival Merck by gaining the first European approval in the field of PD-1 immunotherapy.

The decision also makes BMS' Opdivo (nivolumab) the first PD-1 checkpoint inhibitor to be approved via an accelerated assessment in Europe, signalling the European Commission's attempts to keep up with the US FDA, which has cut approval times via the Breakthrough Therapy Designation route.

The approval is also significant in that Opdivo has been approved as a first-line treatment – one step further than US approvals for it and Merck's rival Keytruda (pembrolizumab), which are only approved for when patients fail existing treatments.

Opdivo has been approved to treat first-line and previously treated advanced melanoma, regardless of BRAF status, a mutation which plays a key role in the disease.

The approval is a coup for BMS in its battle for domination of the PD-1 inhibitor market in melanoma treatment, in which Merck's rival drug Keytruda (pembrolizumab) won US approval last September, ahead of Opdivo in December.

The European market is not as crucial as the US but is, nevertheless, significant in the marketing battle within PD-1 inhibitors and a wider immuno-oncology field, which analysts forecast will be worth at least $20 billion a year by 2022.

However analysts Morningstar recently predicted the market would be a much larger $33 billion by this date, and forecast that BMS would emerge as the leader with Opdivo.

Opdivo's EU approval was based on two pivotal phase III CheckMate trials, 066 and 037.

CheckMate 066 was conducted in patients with previously untreated metastatic melanoma (and without BRAF mutations). The results showed a 1-year survival rate of 73 per cent with nivolumab versus 42 per cent with dacarbazine, with a hazard ratio of 0.42 (P < .0001). The most common treatment-related adverse events with nivolumab were fatigue (20 per cent), severe itching (17 per cent), and nausea (16.5 per cent).

CheckMate 037 was conducted in patients previously treated with and progressed while receiving BMS's existing Yervoy (ipilimumab) and, if BRAF mutation-positive, a BRAF inhibitor. The trial showed a 32 per cent improvement in overall response rate (ORR) compared to investigator's choice chemotherapy, but overall survival data is not yet ready from the study.

Lung cancer and prices

An even more important cancer type for the new drugs is non-small cell lung cancer (NSCLC), and Opdivo gained FDA approval to treat patients with metastatic squamous NSCLC with progression on or after platinum-based chemotherapy, with Keytruda expected to gain a similar approval shortly.

Meanwhile, the question of the price of the drugs – and possible combination treatments such as Yervoy + Opdivo – is a major issue for their uptake in the US and Europe.

BMS will now go full steam ahead into pricing and reimbursement negotiations in Europe and, as such, hasn't declared its intentions on European prices.

Both Opdivo and Keytruda cost around $150,000 for a year's treatment, but European prices are expected to be significantly lower than this. Nevertheless, Europe's oncologists and payers are likely to take a more conservative approach to using the new drugs compared to their US counterparts.

At the beginning of June, the UK regulator the MHRA granted Opdivo approval through its new Early Access to Medicines Scheme (EAMS), for use in advanced melanoma; this followed the approval of Merck's Keytruda via the same route in March. The EAMS route is another new accelerated pathway in Europe aimed at speeding access to new medicines, but whether or not it will have a significant impact on uptake is yet to be seen.