The two furthest developed PCSK9 inhibitors have had very similar clinical development timelines. Sanofi and Regeneron’s alirocumab and Amgen’s evolocumab both began Phase III studies in January 2012 and both received their first regulatory approval in the same month – alirocumab from the FDA and evolocumab from the EMA. Evolocumab also recently received FDA approval in August. The development path of the PCSK9s has been similar to the recent development of novel oral anticoagulants. The latter gained approval in numerous smaller indications and ultimately expanded their market potential with approval for stroke prevention in atrial fibrillation. The real potential in the PCSK9 class will be in preventing cardiovascular outcomes. The two approved drugs as well as a third unapproved drug, Pfizer’s bococizumab, are all currently undergoing cardiovascular outcomes trials (CVOT).
Pfizer began development of bococizumab early, joining Sanofi and Regeneron by entering Phase I in November 2009. Pfizer quickly fell behind the other companies and did not begin Phase II until a month after Amgen and six months after Sanofi and Regeneron. Things only got worse in Phase III as bococizumab development lagged nearly two years after its competitors, so it would seem that Pfizer is quite a bit further behind and at a significant disadvantage. But as mentioned that the real potential is in CV outcomes, Pfizer is positioned to make up quite a bit of the lost ground if we look into the details of each CVOT (Table 1). Amgen is on target to be the first company to complete its CVOT as they have finished enrolling over 27,500 patients and are scheduled to complete the FOURIER trial by October 2017. Sanofi and Regeneron continue recruiting the 18,000 patients for the ODYSSEY OUTCOMES trial and are still reporting expected completion in December 2017. Pfizer is conducting two separate CVOTs (SPIRE 1 and 2) totaling 26,000 patients and the last is anticipated to complete in April 2018, just four months after Sanofi/Regeneron and six months after Amgen. Pfizer may be more than happy to let the other companies wage the initial ugly battles with each other and payers as these drugs slowly find their place in the marketplace.
While Pfizer will not win the race and is certainly disappointed to have lost its early mover advantage, the company’s later entry can allow it to remain unscathed and learn lessons from the others before the market truly expands if and when substantial reduction of CV outcomes becomes a reality for these drugs.