How Vas Narasimhan views a pair of readouts in Novartis’ growth strategy 

CEO of Novartis breaks down major data readouts for Scemblix and remibrutinib this week

Raising the bar for efficacy, differentiating on safety and tolerability, and concentrating small molecule development on indications with minimal IRA exposure are all pieces of Novartis CEO Vasant Narasimhan’s strategy to break into the top pharmas by U.S. sales. 

Two data readouts this week — one for Scemblix asciminib presented at the American Society of Clinical Oncology (ASCO) conference and one for remibrutinib presented at the European Academy of Allergy & Clinical Immunology (EAACI) Congress — may tee up two launches to advance that goal through a strategy focused on prioritizing blockbuster-bound programs. 

On a special episode of The BioCentury Show, Narasimhan describes where he envisions Scemblix asciminib, an allosteric BCR-ABL binder, fitting into the treatment paradigm for newly diagnosed chronic myelogenous leukemia (CML) patients.

Though the goal of a frontline therapy is in sight, he says, the idea of bringing patients off therapy all together is at least five to 10 years away. Still, the future vision encompasses treatment-free periods and will likely involve endpoint innovation.

In frontline CML, Novartis’ first-generation BCR-ABL inhibitor Gleevec imatinib — a drug approved three years before Narasimhan joined the pharma in 2005 — remains a treatment of choice, but it fails to adequately control the disease in many patients. Second-generation tyrosine kinase inhibitors trade off adverse events for higher efficacy, according to Narasimhan. Scemblix is approved for third-line Philadelphia chromosome-positive CML.

The ASCO data position Scemblix as a new option that bests Gleevec on efficacy while offering safety advantages over both classes.

“Now I think most clinicians would say the second-gen TKIs are much more onerous from an adverse event profile, so that’s where the safety comes in. You have a much more high efficacy versus Gleevec, and a safer medicine versus second-gen TKIs,” Narasimhan said.

As safer, more effective therapies reach earlier lines of treatment across cancers, the treatment goals are beginning to shift from lengthening on-treatment survival times to long-term off-treatment remissions, or even functional cures. Narasimhan believes that could be a possibility in the future. 

There’s evidence from the study that Scemblix increases the rate of deep molecular responses — the proportion of patients who meet an even lower threshold for detectable cancer cells. 

“We think that deep molecular response is what will lead to functional cure,” said Narasimhan. However, he said physicians are primarily focused on duration of response and maintaining major molecular response through 96 weeks. 

This week, Novartis also presented Phase III data for Btk inhibitor remibrutinib in chronic spontaneous urticaria at the EAACI Congress.

The inflammatory disease program would fill a hole in the company’s product portfolio, which hasn’t seen the launch of a major new inflammatory disease drug in nearly a decade, since the 2015 approval of Cosentyx secukinumab to treat psoriasis. It also offers pipeline-in-a-product potential, though Narasimhan believes the initial urticaria indication could become a major value driver itself. 

“There’s certainly the possibility that urticaria is significantly underdiagnosed,” he said. “How many patients are not treated simply because they don’t want to go on a biologic, or are undertreated? There could be a much larger market opportunity than what we currently estimate in this 1.5 million to 2 million patients.”

Narasimhan sees both Scemblix and remibrutinib as part of the company’s strategy to become one of the top pharmas by U.S. sales, a goal he believes the company is on track to meet.