Over the course of 2018, Narasimhan set out a more explicit focus on complex therapies, overseeing buyouts of gene therapy specialist AveXis and the radiopharmaceutical company Endocyte.

Those deals, which combined cost Novartis nearly $11 billion, were coupled by exits or planned divestments in consumer healthcare, generic drugs, anti-infectives and eye care.

“Historically, we’ve been in a world of small molecules and large molecules,” the executive said Monday. “My goal over the course of this past year has been to expand the game board.”

Each area of cell therapy, gene therapy and radiopharmaceuticals presents unique commercial problems to solve, however. So far in CAR-T cell therapy, at least, those challenges have proved a reality check to how quickly Novartis can realize its ambitions.

“We clearly had a bump in the road in terms of learning how to scale up the manufacturing,” admitted Narasimhan, in reference to Kymriah (tisagenlecleucel).

While Novartis has been able to successfully deliver the CAR-T therapy to patients, out-of-specification manufacturing data have meant the pharma hasn’t always been able to charge for the pricey treatment.

Impacted by those difficulties and challenges with reimbursement, commercial returns to date for Kymriah have been modest compared to expectations. Sales through the third quarter totaled $48 million, leaving a long runaway ahead of a therapy discussed in the past as capable of $1 billion-plus in annual revenue.

Partly in response — but also with eyes to securing future supply — Novartis has expanded operations in Stein, Switzerland, made a bid to acquire CellforCure and inked partnerships with CBRI in Japan and Cellular BioMedicine in China.

“We have been consistently investing to build up this manufacturing footprint,” Narasimhan said. “We can use this manufacturing footprint for CAR-Ts in cancer, but we can also use it for other lentiviral-based cell reprogramming or other reprogramming approaches that arise in the future.”

What those may be is not yet clear. Novartis’ pipeline lists 8 clinical CAR-T cell therapy programs, all in oncology. Narasimhan mentioned allogeneic CAR-Ts as one area of preclinical research.

In gene therapy, Novartis awaits the FDA’s verdict on Zolgensma (onasemnogene abeparvovec), a one-time treatment for spinal muscular atrophy that raises similar questions around cost and manufacturing.