Novartis announced today the early termination of the ALTITUDE trial, which was testing the effect of the direct renin inhibitor aliskiren (Rasilez, Tekturna) in type 2 diabetics at high risk for cardiovascular and renal events. The action was based on the recommendation of the independent Data Monitoring Committee (DMC), after it found an increased risk for non-fatal stroke, renal complications, hyperkalemia, and hypotension in patients taking aliskiren after 18-24 months. Patients in ALTITUDE were randomized to receive aliskiren or placebo in addition to an ACE inhibitor or an angiotensin receptor blocker (ARB).
The company is also recommending that physicians not prescribe drugs containing aliskiren with either an ACE inhibitor or an ARB. Patients who are already taking a combination pill should be switched to an alternative anti-hypertensive regimen, according to the company.
The action represents a major setback for a drug that had once been thought to have blockbuster potential. Novartis said it was immediately ceasing all promotion of products containing aliskiren and was talking with health authorities about the implications of the findings.
Aliskiren was first approved in 2007 for the treatment of hypertension. Novartis said that total sales for Rasilez and Tekturna were $449 million for the first 9 months of 2011.
John Osborne, a cardiologist in Dallas, TX, sent the following comment to CardioBrief:
The Novartis hypertension franchise is now DOA, obviously. Furthermore, this class of DRIs has died with the death of this drug. There may be the very rare patient on an aliskerin-based product for hypertension that are not on an ACEI or ARB, but that population is going to be very, very small. Furthermore, given this data, why would one use this molecule anyway? In a larger sense, this is also the final nail in the coffin of any kind of a dual RAAS inhibiting/blocking strategy. This also kills off the idea of Plasma Renin Activity as a useful biomarker in hypertensive patients.
These study results are quite remarkable and unexpected and will be one of the top CV stories of 2011, much as AIM-HIGH rocked the lipid community.
Here is an email message from Novartis received by a cardiologist:
From: NovartisSpeakerPortal <NovartisSpeakerPortal@ahmdirect.com>
Date: December 20, 2011 9:15:42 AM CST
Subject: Urgent message about Aliskiren Speaker Programs
Novartis Pharmaceuticals Corporation
One Health Plaza
East Hanover, NJ 07936-1080
December 20, 2011
Novartis is writing to inform you that as a precautionary measure, in the best interest of patients, we have temporarily ceased promotion of Tekturna and all aliskiren-based products for use in combination with an ACE or ARB. This includes ceasing promotion of Valturna.
We have subsequently suspended all branded and unbranded promotional educational programs supporting Tekturna, Tekturna HCT, Tekamlo, Amturnide and Valturna.
Healthcare professionals should not combine an Aliskiren containing product with an ACE or an ARB. Therefore healthcare professionals should switch patients who are on Tekturna or any aliskiren-based products, in combination with an ACE or an ARB, to an alternative anti-hypertension regimen. This includes switching all patients on Valturna to an alternative therapy. This change should take place as soon as medically feasible, consistent with patient safety and the prescribing physician’s clinical judgment.
These actions are being taken following an interim review of data from the ALTITUDE clinical trial. This was the first study to investigate Tekturna for more than one year in a specific population of patients with type 2 diabetes and renal impairment. In the study, Tekturna was given in addition to optimal cardiovascular treatment including an ACE inhibitor or ARB.
Novartis was informed that the independent Data Monitoring Committee (DMC) overseeing ALTITUDE had recommended stopping the trial because Tekturna was unlikely to show any benefit, and potential safety concerns had been identified in these high-risk patients. Specifically, Tekturna was associated with an increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension .
In view of the unexpected study findings, a decision was taken to terminate the ALTITUDE study. Patient safety is the highest priority for Novartis and we are in dialogue with health authorities worldwide. We are now assessing the results of the ALTITUDE study and the potential implications for aliskiren-based products.
For additional information or to ask questions, healthcare professionals can call Novartis Medical Information and Communications toll free at 877-263-6725.
Head, Cardiovascular/Metabolism & Inflammation Medical Unit
Novartis Pharmaceuticals Corporation