Novartis posts pivotal data ahead of FDA decision on $9.7B bet

Novartis CEO Vas Narasimhan 2019
Novartis CEO Vas Narasimhan (Novartis)

Novartis has published the phase 3 data it hopes will secure approval of cholesterol drug inclisiran. The trials linked the siRNA therapy to sharp declines in levels of LDL cholesterol, shedding more light on why Novartis decided to pay $9.7 billion to get its hands on the drug.

Last year, The Medicines Company posted data from three phase 3 trials of inclisiran in patients with atherosclerosis or heterozygous familial hypercholesterolemia. In doing so, Medicines Company was able to frame inclisiran as a drug capable of matching the efficacy, and beating the convenience, of anti-PCSK9 antibodies sold by Amgen and Regeneron and Sanofi.

That prospect led Novartis to strike a $9.7 billion deal to acquire Medicines Company, gambling that combining the inclisiran data with its cardiovascular sales force would result in sales far beyond those achieved by floundering anti-PCSK9 antibodies Repatha and Praluent.

Now, researchers have set out the current evidence on inclisiran in two papers published in The New England Journal of Medicine. One of the papers covers two phase 3 trials in atherosclerosis, while the other addresses the heterozygous familial hypercholesterolemia study.

As previously reported, the studies met their primary endpoints, with declines in LDL of around 50% suggesting inclisiran is competitive on the efficacy front. The trials were also free from the safety red flags observers feared may be raised by the use of the siRNA therapy. 

Medicines Company filed for FDA approval on the strength of the pivotal data late last year. Novartis’ willingness to bet $9.7 billion on the company is testament to the belief that inclisiran is well placed to win approval. However, limitations of aspects of the data mean it remains unclear what evidence Novartis will have at its disposal as it tries to turn inclisiran into a big seller.

Notably, the overall numbers of deaths in the treatment and control arms of the atherosclerosis trials were similar, depriving Novartis of the chance to make strong claims about outcomes in its early sales push. The authors of the NEJM paper downplayed the finding, stating that “the total number of nonadjudicated cardiovascular events observed was too small to draw meaningful conclusions about any potential benefits of inclisiran on cardiovascular outcomes.”

That will remain the case for some time. Novartis is running an inclisiran cardiovascular outcomes trial, ORION-4, but the estimated primary completion date for that 15,000-patient study is listed as December 2024.