Novartis will terminate the late-stage ALTITUDE study investigating Rasilez (aliskiren) in patients with type 2 diabetes and renal impairment on the recommendation of an independent data monitoring committee. The company indicated that the committee concluded that "patients were unlikely to benefit" from the addition of Rasilez to standard anti-hypertensives and also identified higher adverse events in this group.
"The finding comes very unexpected," commented Vontobel analyst Andrew Weiss, who had forecast peak annual sales for Rasilez of as much as $2.9 billion, assuming that the drug would have additional benefits for key organs if taken over a long period of time. Weiss said he now plans to reduce his sales estimate for the product. Meanwhile, there were suggestions that Novartis could accelerate plans to reduce its US workforce, with Deutsche Bank predicting that the drugmaker may cut up to 1000 sales jobs as a direct result of the study failure.
The trial, which included 8,606 patients with type 2 diabetes and renal impairment, was designed to evaluate the potential benefits of Rasilez to reduce the risk of cardiovascular and renal events. In the study, Rasilez was given in addition to optimal cardiovascular treatment including an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Novartis said the trial was the first to investigate Rasilez for more than one year in this specific patient group.
However, the drugmaker noted that in patients given Rasilez in combination with standard of care, "there was an increased incidence after 18-24 months of non-fatal stroke, renal complications, hyperkalemia and hypotension." Novartis indicated that it is in talks with health authorities regarding the implications of the findings, and in the meantime will stop promotion of products containing Rasilez for use in combination with an ACE-inhibitor or ARB. Spokesman Eric Althoff said the company is also looking at the data of other similar trials, which are currently ongoing.
Novartis suggested that sales of Rasilez, which is marketed as Tekturna in the US, "are likely to be negatively impacted by the study results going forward." According to the company, revenue for Rasilez-based products for the first nine months of 2011 reached $449 million, although "product profitability" in the year was negative.
The product was approved in 2007 in the EU and US for the treatment of hypertension either as a monotherapy or in combination with other therapies. The drugmaker has been looking to expand use of the agent, and has launched several trials to examine if the compound could protect organs such as kidneys and the heart if taken over a longer period of time.