Shares in Roche have taken a bashing after the Swiss major has pulled the plug on dalcetrapib, a drug which raises 'good' cholesterol, after suffering a late-stage study failure.
On the basis of results from the second interim analysis of the dalcetrapib dal-OUTCOMES Phase III trial, the independent data and safety monitoring board has recommended stopping the study due to a lack of clinically meaningful efficacy. The more-than-15,000-patient trial evaluated the drug, a cholesterylester transfer protein (CETP) inhibitor, when added to existing standard of care in patients with stable coronary heart disease following an acute coronary syndrome.
No safety signals were reported but Roche has decided to terminate the study and the entire six-trial dal-HEART programme, two of which have been completed. Over 35,000 patients were involved in the studies.
Roche chief medical officer Hal Barron noted that "lowering cardiovascular risk beyond that which is achieved with intensive statin treatment is a very challenging goal". He added that "while we have always stated that dalcetrapib is a high-risk project, we are disappointed by the fact that this drug didn't provide benefit to the patients in our study".
Dr Barron went on to say that "we continue to be fully committed to the development of innovative medicines for people with cardiovascular disease". He noted that "our pipeline remains robust with 23 positive late-stage clinical trials reporting over the past 16 months and a significant increase in new molecular entities in late-stage development".
The CETP inhibitors has suffered setbacks in the past as at the end of 2006, Pfizer terminated torcetrapib in Phase III due to safety concerns. There are still some well-advanced drugs left in this class, however, namely Merck & Co's anacetrapib (Phase III) and Eli Lilly’s evacetrapib (just completed Phase II).
CETP questioned but analysts back Merck's anacetrapib
Nevertheless, the failure of dalcetrapib has led a number of observers to call into question the CETP class, which is seen by some as the next step forward from statins in terms of treating heart disease. Tim Anderson, an analyst at Sanford Bernstein issued a research note saying that "experts in the field of cholesterol management have remained uncertain about the general approach of raising HDL-cholesterol through CETP inhibition. Investors have also remained cautious".
Mr Anderson still believes "there is a 'bull case' to be made" with anacetrapib because "it seems to lack the safety problems of torcetrapib, and unlike dalcetrapib that only raised HDL (good) cholesterol, Merck's drug both raises HDL and lowers LDL (bad) cholesterol". He concluded by saying that "it is possible that the LDL lowering alone could carry anacetrapib across the finish line".
As for Roche, the loss of dalcetrapib, touted as a blockbuster, is a blow, though analysts already had fairly low expectations. Investors were disappointed, however, and the Basel-based firm's shares fell nearly 3.5% to close at 159.40 francs.