Just as the first generation of checkpoint inhibitors have dominated this year's annual meeting of the American Society of Clinical Oncology (ASCO) – for the third year in succession – analysts are bullish that these products will play a prominent role in shaping the commercial landscape through to the end of the decade.
Consensus forecasts indicate that Bristol-Myers Squibb's PD-1 inhibitor Opdivo (launched last year) will generate global sales of $6.2 billion by 2020, while Merck & Co.'s Keytruda is expected to achieve revenues of $3.6 billion in the same year. According to consensus, two other PD-1/PD-L1 inhibitors will have achieved blockbuster status by the end of the decade, with Roche's MPDL3280A and AstraZeneca's MEDI4736 expected to achieve sales of $2 billion and $1.5 billion, respectively.
How accurate these forecasts prove to be remains to be seen, with new data presented this weekend at ASCO poised to subtlety shift the commercial dynamic of the PD-1/PD-L1 inhibitor class. To the disappointment of investors (who sent the company's share price down 6.5 percent) Bristol-Myers Squibb's much anticipated Checkmate-057 study – assessing Opdivo for non-squamous non-small cell lung cancer (NSCLC) – showed a survival benefit only in those patients expressing the PD-L1 biomarker. No benefit was demonstrated in the 40 percent to 45 percent of patients lacking this biomarker.
The Checkmate-057 study results not only raise questions about the commercial opportunity for Opdivo in lung cancer but Bristol-Myers Squibb's stance towards PD-L1 testing in this indication. "Investor consensus has clearly been skewed towards believing in Bristol-Myers Squibb's point of view (which has minimised the importance of PD-L1 testing) as evidenced by consensus estimates for Opdivo substantially exceeding those of its competitors," wrote Bernstein analyst Tim Anderson in a note to investors published on Friday.
Not only is the playing field for the PD-1/PD-L1 inhibitors "likely to be more level than this," adds Anderson, but PD-L1 testing could emerge as a "potential point of differentiation and a possible source of market or pricing/reimbursement advantage." Notably, in addition to positioning PD-L1 testing at the centre of development and commercial strategies from the outset, both Merck & Co. and Roche are now advancing I/O biomarker testing beyond PD-L1 status.
Within the next five years, Roche will concede long running possession of the biggest selling oncology brand (Rituxan, Avastin and Herceptin were the three largest franchises in 2014 with combined sales of $21 billion), with Celgene's multiple myeloma therapy Revlimid expected to emerge as the industry's first $10 billion-a-year cancer product by 2020.
The Swiss company will, however, remain both market leader and powerhouse in the oncology segment. While combined Rituxan, Avastin and Herceptin sales are forecast to decline steadily to around $16 billion by 2020, Perjeta, Gazyva, Kadcyla and MPDL3280A will contribute combined sales of around $10 billion.
Perjeta, which is rapidly becoming established as the gold standard first-line treatment for HER2-positive breast cancer in combination with Herceptin, is expected to generate sales of over $4.5 billion by 2020. Kadcyla, despite lack of progression into first-line usage, is still expected to achieve blockbuster sales on the strength of second-line usage in HER2-positive patients.
Approved by the FDA earlier this year, Pfizer's breast cancer treatment Ibrance is expected to generate revenue of around $4.7 billion by 2020, with consensus forecasts supported by recent claims that the drug is poised to become the fastest new oncology launch of all time. Pfizer presented additional positive data for Ibrance this weekend at ASCO.
Another recent launch expected to achieve significant revenue expansion over the next five years is Imbruvica; now co-marketed by AbbVie and Johnson & Johnson following the former's acquisition of Pharmacyclics earlier this year. Analysts have so far bought into the bullish expectations of AbbVie in particular, with revenue expectations having risen steadily in recent months to stand at around $8 billion by 2020.
The exposure of leading cancer brands to generic or biosimilar competition will be relatively limited through to 2020, with Novartis' Gleevec and Johnson & Johnson's Velcade the notable exceptions. A combination of Gleevec's profile as one of the most effective cancer therapies ever launched and its status as a small-molecule product will see sales rapidly eroded when multiple generic versions reach the market; revenues are expected to plummet from $4.7 billion in 2014 to around $570 million by 2020.
Exposure of certain brands – notably Roche's Herceptin and Rituxan franchises – to biosimilar competition will be watched with much interest. Some analysts have argued that motivation to use biosimilars (and save costs in the process) will be enhanced by the emergence of new, expensive therapies, such as the PD-1/PD-L1 inhibitors, and compelling evidence to suggest these are most effective when used in even more costly combinations.
Roche is more bullish on the sustainability of Rituxan and Herceptin revenues, citing delayed market entry for biosimilars, steep uptake for a recently launched subcutaneous version of Herceptin and gradual adoption of biosimilar products by cautious oncologists.
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