Gene testing is shaping up to be a marketing battleground for new blood thinners like AstraZeneca's Brilinta, underscoring the power and limitations of genetics as a tool to predict medical outcomes.
The arrival of generic copies of Sanofi-Aventis and Bristol-Myers Squibb's top-seller Plavix makes the issue a hot topic scientifically and commercially, new studies at the European Society of Cardiology congress on Sunday showed.
One study found AstraZeneca's Brilinta, unlike Plavix, requires no genetic testing to check if it will work, while another showed Eli Lilly and Daiichi Sankyo's Effient also worked irrespective of gene variations.
On the face of it, the results of the two company-sponsored trials give the firms valuable ammunition in a looming marketing war with cheap copies of Plavix, or clopidogrel.
Physicians don't like complications, so if there was an alternative to clopidogrel that worked the same way that did not have these variations then most people would jump on it, said Alfred Bove of Philadelphia's Temple University School of Medicine.
But the evidence is far from clear-cut. A third study, sponsored by Sanofi and Bristol, contradicted the idea that people with a certain genetic make-up don't benefit from Plavix.
The stakes are high because Plavix is the world's second biggest drug, with sales last year of more than $9.5 billion. The drug is already off patent in parts of Europe and will lose U.S. patent protection in 2012.
BRILINTA AWAITS APPROVAL
AstraZeneca believes Brilinta is better than either Plavix or Effient, which has been linked to higher bleeding risk, and is hoping the new gene data will add another string to its bow.
Brilinta is expected to win a green light to go on sale in the United States as early as next month, after being endorsed by a U.S. advisory panel last month.
An analysis of more than 10,000 patients in the PLATO study found Brilinta cut the risk of heart attacks, strokes and cardiovascular deaths more than Plavix, whether or not they had a genetic variability that has been previously shown to affect a patient's response to clopidogrel.
The Effient study showed similar lack of impact from gene variations, based on a smaller analysis of data from the TRITON study. Both studies were published in The Lancet journal.
The link between Plavix response rates and genetics hit the headlines in March, when the U.S. Food and Drug Administration warned that some patients have a poor response to the drug because they do not break it down well.
European regulators have not yet followed suit and Gilles Montalescot of Hospital Pitie-Salpetriere in Paris said more studies were needed before conclusions could be drawn about the value of widespread genetic profiling.
That uncertainty was underlined by the third study, in the New England Journal of Medicine, showing no difference between poor metabolisers of Plavix and others among 6,000 participants from two other trials, CURE and ACTIVE.
The lead researcher of that study, Guillaume Pare, said it added a further layer of complexity, by showing that reported genetic variants had no effect in certain patient populations.
The whole field is in flux, said David Holmes of the U.S. Mayo Clinic in Rochester, commenting on the three studies.
Everybody would like to think that personalized medicine is going to be perfect. We just don't have chapter and verse to make sure that's the case.
Robert Califf of Duke University School of Medicine said it appeared genetic variability was probably important for sicker patients, including those having a stent to prop open clogged arteries, but was less significant for lower-risk patients like those in the CURE and ACTIVE studies.
For AstraZeneca, the dynamic situation means the company will have to carefully balance superiority claims against the price it plans to charge for Brilinta, medical experts said.
It's probably better to have more of your drug on the market at half the price you thought it was going to be than take 10 years to get it adopted, said Bove.