Novartis’s case for additional approval of canakinumab in cardiovascular disease has been built around an analysis demonstrating a clinically relevant benefit in patients showing a strong biomarker response. This case could be bolstered with additional data cuts in kidney disease and diabetes.
The American College of Cardiology conference in March will feature late-breaking data readouts from the Cantos study in these subgroups; the co-morbid conditions are independent risk factors for subsequent myocardial infarctions and strokes. If canakinumab shows a benefit here, regulators could be more easily persuaded that the injection is an important addition to cardiovascular treatment protocols – not to mention payers, who will need to see an economic value.
When the Cantos trial first read out canakinumab’s results in an all-comer population of post-MI patients with elevated levels of high-sensitivity c-reactive protein (hsCRP) – a 15% reduction in major adverse cardiovascular events among those taking a 150mg dose – were judged less than impressive.
An analysis indicating a stronger response among those achieving hsCRP levels of 2mg/l or less after three months gave Novartis a path to regulatory submission. A major drawback is that payers almost certainly will not want to pay for any patients who do not achieve this response (Novartis homes in on heart biomarker for canakinumab, November 14, 2017).
Should the anti-inflammatory effect of canakinumab, trademarked Ilaris, have a pronounced benefit in diabetic and chronic kidney disease patients, it should give regulators less reason to say no and help payers swallow a hefty price in a wider patient pool – especially given that cardiovascular disease goes hand-in-hand with these two conditions.
The diabetes data will come from a pre-planned substudy that measured the change in the insulin secretion rate among patients already taking glucose-lowering drugs. A previous phase II/III trial in 551 patients showed a numerical, although not statistically significant, benefit for Ilaris treatment plus metformin compared with metformin alone – researchers speculated that the anti-inflammatory mechanism of Ilaris improved beta-cell function.
The full Cantos trial enrolled 10,000 patients, and with this pre-planned substudy in mind it is probable that the number of type 2 diabetics exposed to canakiumab was greater than in the small trial, improving the odds of a statistically significant result if the numerical effect is repeated. If canakinumab can, in fact, improve glucose control in addition to preventing cardiovascular events it will be of great interest to physicians specialising in metabolic disease.
A stake in kidney disease
Chronic kidney disease, meanwhile, is an independent risk factor for myocardial infarction, and patients are more likely to die from cardiovascular disease than from kidney failure. Statins, meanwhile, can cause kidney-related side effects even though they are recommended as a treatment in this patient group.
At a minimum, Novartis will hope that canakinumab will prove to be safe in this population while demonstrating a similar cardiovascular benefit to the broader responder population – whether lowering levels of hsCRP could have an effect on kidney disease progression would be speculative as renal outcomes were not pre-specified.
In its currently approved rare disease indications Ilaris costs $200,000 a year, but Novartis's chief executive, Vas Narasimhan, has hinted at a lower price in cardiovascular indications. His executive team will be keenly aware that the company's competition is off-patent statins and Zetia – thus pursuing the all-comer population was regarded as a non-starter.
This lower price could prove problematic if canakinumab's interleukin-1 blockade shows efficacy in cancer treatment, where early trials under are way and pivotal studies planned.
Pricing is an issue for the future, however, and for now narrowing the focus to the best hsCRP responders gives canakinumab the best chance of success in heart disease. Still, canakinumab can use all the help it can get, and ACC will show how strong Novartis’s case will be.
|Major canakinumab presentations at ACC|
|Cardiovascular efficacy in chronic kidney disease, March 11||407-14|
|Canakinumab and type 2 diabetes, March 12||408-10|
To contact the writer of this story email Jonathan Gardner in Virginia at firstname.lastname@example.org or follow @ByJonGardner on Twitter. Jon will be reporting from the ACC conference taking place March 10-12 in Orlando, Florida.