|24th August 2016
Bristol-Myers Squibb's (BMS, $BMY) immunotherapy wonder drug Opdivo (nivolumab) was poised for lasting success. The immuno-oncology treatment won an accelerated FDA approval for metastatic melanoma in December 2014, and has since proved to be a thriving sensation. Until things took a turn for the worse.
Opdivo works via PD-1 immune checkpoint inhibition, which involves reactivating T-cells (a subtype of white blood cell) and decreasing tumor growth. In this manner, it can crucially target several cancers, a property that was successfully exploited by BMS and resulted in securing FDA nods for treating non-small cell lung cancer (NSCLC) and renal cell carcinoma (kidney cancer). Impressively, Opdivo consistently outperformed Merck & Co.'s ($MRK) Keytruda (pembrolizumab), racking up $1.58 billion in sales during the first half of 2016 compared to $563 million earned by its main rival. Observers of its soaring trajectory projected Opdivo to be second in order of top selling pharmaceutical products in Europe in 2022, with €2.4 billion in sales.
Their success story wasn’t to remain untarnished forever. Some chinks in the Opdivo armor were evident back in June 2016, but were largely overlooked. Back then, the UK’s cost-effectiveness watchdog NICE deemed Opdivo too pricey for renal cell carcinoma when taking into account the availability of Pfizer's Inlyta at a markedly lower price. Then, in August 2016, BMS announced disappointing results from a Phase III clinical trial – Opdivo had failed to significantly improve progression-free survival (PFS) when used as a first-line treatment for NSCLC. Their share price plunged by 17%, while competitor Merck & Co.'s surged by more than 10%. Rubbing salt into BMS’s wounds, Merck's Keytruda snagged a new FDA approval in head-and-neck cancer.
As tremors of uncertainty reverberated in the global markets, analysts dramatically slashed Opdivo’s profit forecasts and doctors and drug executives unfavorably recalibrated their expectations for Opdivo.
As far as the first line setting is concerned, it sets in motion the exploration of opportunities by therapies such as AstraZeneca and MedImmune’s durvalumab, Pfizer and Merck's avelumab and Roche’s Tecentriq that were regarded second string up to this point. Inauspiciously for BMS, it opens the door for Keytruda to both entrench itself in the first-line setting and infiltrate the second-line, the latter undisputedly dominated by Opdivo until now.
Moreover, in a recent survey conducted by FirstWord Pharma, physicians not only tepidly supported Opdivo after its recent failure, but also stated that they were willing to test Keytruda in a wider patient population. Significantly, it seems that one of the hurdles that held Keytruda back – the requirement for a tedious diagnostic test for “high expressers” of the PD-L1 biomarker – has been overcome with time-challenged physicians expressing greater willingness to carry out the companion test.
Despite daunting challenges faced by BMS, the future for Opdivo may not be as bleak as it seems. Despite being shot full of holes at present, there are many reasons to believe that it will not only recover, but could also reinstate its position of leadership in immuno-oncology. Opdivo’s lifecycle management has so far been nothing short of spectacular, with indication expansions coming thick and fast in the space of just two years. Opdivo is now also approved by the FDA for the treatment of patients with classical Hodgkin’s lymphoma (cHL) and, pending EMA validation, has the potential to become the first PD-1 inhibitor approved for the hematological malignancy in the EU. It is also being tested in several ongoing clinical trials, both by itself and in combination to Yervoy, another BMS oncology product.
Lastly, BMS’s clinical trial approach for NSCLC should be applauded for aspiring to meet clinical endpoints significantly more ambitious than any other competitor. Their decision – both on ethical and business grounds – to run the recently failed NSCLC trials with the patients’ inclusion threshold at merely 5% PD-L1 tumor level meant that a broader population could benefit from it. Merck were content to set Keytruda’s corresponding threshold at 50%. Had BMS been successful, it would have been a triumph for personalised medicine.
Opdivo is by no means dead in the water. Once it comes out of this tumultuous period, it should continue its stratospheric ascent in the immuno-oncology space.
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