Bristol-Myers and Pfizer ring in 2013 with Eliquis approval

Despite a delay, US regulatory backing had long seemed a fait accompli for Bristol-Myers Squibb and Pfizer’s Eliquis, but the FDA delivering its verdict three months ahead of the latest deadline was the icing on the cake. Eliquis is now approved in the key stroke prevention indication with the best label of all of the new generation of blood-clot prevention drugs.

With Japan’s positive decision also coming near the year’s end, the two big pharma groups could bid farewell to 2012 with the knowledge that a big growth driver – Bristol-Myers’ biggest – will soon be on sale in the three largest drug markets. The US launch will now be closely tracked; even with warfarin proving resilient to the challenge of Pradaxa and Xarelto, expectations for Eliquis remain sky-high.

Big decision

The Eliquis decision announced post-market on December 28 was important enough to move the needle on Bristol-Myers’ market capitalisation. Shares in the New York group closed 2% higher at $32.59 on December 31, the first day of trading after the announcement.

This should come as little surprise as the factor Xa inhibitor is forecast to add $3.7bn to Bristol-Myers sales by 2018, nearly all of it to prevent stroke in patients with atrial fibrillation. FDA approval was essential to supporting Bristol-Myers’ valuation, and the table had been set by European Union backing (EU backing for Eliquis in stroke prevention bodes well for US decision, November 21, 2012). Pfizer is forecast to receive $1.8bn in alliance revenue in 2018.

The original complete response letter due to “data management and verification” from the phase III Aristotle trial was a big setback (Eliquis FDA setback turns up the heat on Pfizer and Bristol-Myers Squibb, June 25, 2012). However, prominently featured in the label are data from Aristotle, which showed the factor Xa to be significantly better than warfarin at preventing strokes and systemic embolism while resulting in significantly fewer major bleeding incidents.

Neither of the previously approved single-dose warfarin replacement pills recently approved, Pradaxa or Xarelto, was able to make a claim of superiority on both safety and efficacy. Xarelto can make a claim of non-inferiority on both, while Pradaxa showed superiority in stroke prevention.

Thus despite being late to the market, Eliquis’s forecast $3.7bn in 2018 sales is expected to eclipse Bayer and Johnson & Johnson’s Xarelto at $3.5bn and Boehringer Ingelheim’s Pradaxa at $1.7bn, according to EvaluatePharma data.

Three, possibly four-way race

Still, as the third product to market the challenge should not be underestimated. Wisely, Bristol-Myers and Pfizer announced pricing of $8.35 a day, matching Pradaxa and at a slight premium to Xarelto, which should put Eliquis on a solid competitive footing when sales reps hit the street.

Despite warfarin’s shortcomings, which include a need for individualised treatment and frequent monitoring along with numerous drug interactions, the long-established drug has stood well against the challenge of Pradaxa and Xarelto (Warfarin proves resilient against oral blood thinners, August 21, 2012). Bullish sales forecasts for Xarelto have fallen since its FDA approval in stroke prevention in November 2011, although the consensus forecast has become more optimistic in recent months.

Given physicians’ familiarity with warfarin, their reluctance to switch well-performing patients off the 59-year-old drug, and its generic pricing, the new drugs are likely to go primarily to newly diagnosed patients and established patients who are no longer achieving their anticoagulation goals. Thus being a late starter might be even more of a disadvantage than usual; analysts from Leerink Swann forecast a “relatively slow initial launch that picks up over time”.

The other emerging threat is readout of data from Daiichi Sankyo’s Lixiana, due out in spring 2013. Any signs that the Japanese company’s factor Xa inhibitor could also outperform warfarin on safety and efficacy would change the competitive landscape; findings of non-inferiority, as with Xarelto, would allow Eliquis to “dominate the class”, writes analyst Mark Schoenebaum of ISI Group.

Bristol-Myers was the victim of the biggest patent expiry of 2012, Plavix, and its valuation today is more dependent on its R&D performance than that of many other big pharma groups as the industry passes over the patent cliff. Approval of its biggest growth driver might not have been unexpected, but it must nevertheless come as quite a relief to investors who have put their faith in Bristol-Myers’ pipeline.

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @JonEPVantage on Twitter