FDA approval of the second CDK4/6 inhibitor, Novartis’ (NYSE:NVS) Kisqali, has set up a battle against the current incumbent, Pfizer’s (NYSE:PFE) Ibrance. With both agents showing similar efficacy in phase III, the winner could be determined by other factors like side effect burden, where Ibrance currently looks to have the edge.
Price could also be an important factor in these increasingly cost-conscious times and Novartis has indicated that it is willing to compete here, unveiling what it calls a flexible pricing scheme. Nonetheless, EvaluatePharma consensus still puts Kisqali behind Ibrance in 2022 – and it faces another scrap with Eli Lilly’s (NYSE:LLY) abemaciclib, due to become the third approved CDK4/6 inhibitor (see table below).
There should soon be more data on how abemaciclib stacks up in terms of efficacy, with the phase III Monarch 2 study due to report in the first half of 2017. If positive, a filing should follow later this year.
Lilly had planned to file the product last year, and it had been expected to be one of the biggest approvals of 2016. However, results from the single-arm Monarch 1 trial weren’t as convincing as had been hoped, forcing Lilly to wait for the Monarch 2 read out (Event – Lilly’s abemaciclib fights for silver medal, August 9, 2016).
Since then, forecasts for abemaciclib have been on the decline while those for Kisqali have surged – the two products are now almost neck-and-neck in 2022 according to EvaluatePharma consensus forecasts.
And Kisqali now has approval in combination with an aromatase inhibitor for the first-line treatment of post-menopausal women with hormone-receptor-positive, HER2-negative advanced or metastatic breast cancer.
Ibrance has received accelerated approval in the same population, as well as approval in second-line breast cancer following endocrine therapy, in combination with fulvestrant.
The overall safety profile of the two drugs is similar, Leerink analysts noted, but pointed out that certain monitoring requirements could put Kisqali at a disadvantage. Novartis’ product has warnings on its label for QT prolongation and liver toxicity, both of which require frequent monitoring. Notably, Ibrance’s label does not include these warnings or monitoring requirements.
The “burdensome” monitoring with Kisqali, on top of Ibrance’s first-mover advantage, should mean the latter remains the dominant force in the CDK4/6 inhibitor space, the analysts believe. They estimate that Ibrance will capture around 67% and Kisqali around 20% of the market at their peak.
But pricing is a wildcard and Novartis has set its stall out here, with a spokesperson telling EP Vantage that Kisqali “will be the CDK 4/6 inhibitor with the lowest wholesale acquisition cost price.” The company has set the WAC for a 28-day supply at $10,950 for the 600mg tablets, $8,760 for 400mg and $4,380 for 200mg.
Kisqali will come in at around an 18-20% discount to Ibrance after accounting for dose, according to the Leerink analysts. Novartis will hope this helps it capture market share from Pfizer’s product in spite of the safety disadvantage.
While Novartis and Pfizer fight it out, Lilly risks falling further behind. Even if Monarch 2 is positive, the data will only support a filing in second-line disease, and Lilly will have to wait until later in the year for full results from the first-line Monarch 3 trial.
One way in which Lilly might set its candidate apart is safety: abemaciclib, which is more selective for CDK4 over CDK6, could have a better toxicity profile that would allow continuous dosing. Ibrance requires a one-week “drug holiday” after three weeks of treatment due to its risk of neutropenia, and Kisqali appears to have similar rates of neutropenia to Ibrance.
However, it is not all positive for abemaciclib, which has been linked with gastrointestinal side effects.
Lilly’s drug still has it all to do: as well as needing to demonstrate efficacy in phase III, it will probably also have to show a safety advantage if the company wants to compete in the CDK4/6 inhibitor market. Investors will be eagerly watching the upcoming data to see if a benefit emerges.