Novartis wins a key OK for Kymriah, but continuing manufacturing woes hobble rollout — rival Gilead CAR-T breaks into Europe

Novartis CAR-T manufacturing woes are continuing to put a crimp in its ability to provide therapy to all potential patients.

Vas Narasimhan

The pharma giant reported this morning that the EC has stamped its approval on marketing Kymriah in Europe for B-cell acute lymphoblastic leukemia as well as treatment-resistant adults suffering from diffuse large B-cell lymphoma. But Novartis can only make it available to children with ALL now — adults will have to wait.

Novartis’s top execs have worked hard to smooth things over with analysts, but it’s been bedeviled by manufacturing issues throughout the development stage and continues to be affected as it goes toe-to-toe with Gilead’s Kite, approved for large B-cell lymphoma. And Gilead is still coming on strong, noting this morning that they received a European OK to market Yescarta for diffuse and primary mediastinal large B-cell lymphoma.

A month ago Novartis CEO Vas Narasimhan noted during the Q2 call that:

I think it’s early days and we’ve always said this is going to be a five-year journey with Kymriah to really get us to be the globally successful brand we want it to be.

On manufacturing, we have seen some variability in our product specifications. This is something we’re looking at now in DLBCL to make sure that we can continue to ramp-up the demand. We feel confident in the overall longer-term outlook for Kymriah.

Liz Barrett

Liz Barrett, who runs Novartis oncology, had this to say:

I think the most important thing to let you know is that the variability that we’ve seen in the commercial specifications, which isn’t unusual with a new therapy as you launch into a new target patient population, is that we have still been able to deliver final product to the majority of patients.

As we’ve reported, though, the cell manufacturing chief’s office has been outfitted with a revolving door at Novartis in recent years. Karen Walker left that post in early 2017, followed last spring by Spencer Fisk as he jumped ship to join the Novartis execs at Rubius. Those departures came on top of a major revamp for the cell and gene therapy unit in 2016, which raised questions at the time about Novartis’ ability to keep up with Kite — though the pharma giant wound up with the pioneering first OK. And Novartis’ issues with manufacturing cell therapies extend back to the snafus it experienced with late delivery to a small but significant group of patients enrolled in clinical trials.

At one stage in the development process, Novartis had a 6% failure rate on the manufacturing process in a key clinical trial, which they later said was largely resolved and brought down to 3%.

This morning Novartis is following up with plans to invest €78.8 million into their cell and gene therapy manufacturing operations in Switzerland in their latest stab at fixing the problems.

But after recording only $16 million in sales for Q2, the big question looming for Novartis is why patients would want to take a risk with their therapy if another provider comes into the market which can do better on a complex task: extracting T cells from patients, modifying them and then infusing patients with a therapeutic punch?

You can be sure that the top crew at Gilead and Kite — working with a bespoke manufacturing site — are paying close attention.

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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