Shares in Abbott Laboratories have slipped on the news that a US government study looking at the firm’s lipid drug Niaspan and statin treatment has been halted early because it did not reduce the risk of cardiovascular events, including heart attacks and stroke.
The National Heart, Lung and Blood Institute of the National Institutes of Health has stopped the 3,414-patient AIM-HIGH trial 18 months early following the advice of an independent data and safety monitoring board. The latter concluded that high dose, extended-release Niaspan (niacin) offered no benefits beyond statin therapy alone in reducing cardiovascular-related complications.
Participants had a history of cardiovascular disease and were taking a statin to keep their LDL cholesterol low. Study participants also had low HDL cholesterol and high triglycerides, which meant that they were at significant risk of experiencing future cardiovascular events.
They were randomly assigned Niaspan in gradually increasing doses up to 2,000 mg per day (1,718 people) or a placebo (1,696 people) and all participants were prescribed Merck & Co’s Zocor (simvastatin), and 515 patients were given a second drug, Merck’s Zetia (ezetimibe), in order to maintain LDL cholesterol levels at the target range between 40-80 mg/dL. The rate of clinical events was the same in both treatment groups, “and there was no evidence that this would change by continuing the trial”, the NIH noted.
‘Small, unexplained’ rise in stroke
The DSMB also noted “a small and unexplained increase” in ischemic stroke rates in the Niaspan group. During the 32-month follow-up period, there were 28 strokes (1.6 %) reported during the trial among participants taking the Abbott drug versus 12 strokes (0.7 %) in the control group. However, the NIH stresses that “previous studies do not suggest that stroke is a potential complication of niacin, and it remains unclear whether this trend in AIM-HIGH arose by chance”.
Jeffrey Probstfield of the University of Washington in Seattle and the study’s co-principal investigator, said “the lack of effect on cardiovascular events is unexpected and a striking contrast to the results of previous trials and observational studies”.
The US Food and Drug Administration also issued a statement saying that at this time, it has made “no new conclusions or recommendations regarding the use of extended-release niacin alone or in combination with simvastatin or other statins”. The agency added that it will conduct a comprehensive review of the AIM-HIGH trial data “to determine their impact on the approved indications for extended-release niacin”.
Niaspan is sold on its own and in combination with simvastatin under the brandname Simcor, and in combination with lovastatin as Advicor. First-quarter sales reached $226 million.
Still an ‘important agent’
Eugene Sun, Abbott’s head of global pharmaceutical clinical development, responded to the news by saying that “lipid disorders and cardiovascular disease are complex and varied. Based on its long history of clinical evidence, Niaspan remains an important agent for patients with mixed dyslipidaemia and primary hyperlipidaemia”.
The company claimed that “there are a number of unanswered questions that remain, based on these interim study results” and some of these issues may become clearer when the study database closes in autumn and a comprehensive analysis can be conducted”. Abbott added that “the ischemic stroke data are also inconsistent with what is known about Niaspan’s action as a vasodilator, its effect on platelet aggregation and the drug’s anti-coagulative properties, all of which are inconsistent with stroke causation”.
It concluded by saying that “no stroke safety signals have been seen in post-marketing safety data over more than 6 million patient years of experience”. Investors appear to be a bit spooked, however, and Abbott shares ended the day down 1.6% to $52.14.
