First come, first served: Novartis finalizes CAR-T application, claims priority review

Novartis has made good on its promise to submit a biologics license application (BLA) for its lead CAR-T candidate in the first quarter of the fiscal year. With two days to spare, no less.

According to a statement released on Wednesday, the FDA has accepted the submission and granted Novartis a priority review. That should see a decision returned within six months, instead of the standard 10-month estimate.

The equivalent approval application will be filed with the European Medicines Agency (EMA) later this year, the statement read.

Novartis has been at the front of the pack with its CAR-T program, acquired through a 2012 partnership with the University of Pennsylvania. Its lead CAR-T, CTL019 (tisagenlecleucel-T), traces back to the seminal work of Carl June at the University’s Perelman School of Medicine.

CTL019 is vying for approval to treat children and young adults with relapsed and refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). ALL accounts for around 25 percent of all cancers diagnosed in patients under the age of 15. For the r/r cohort, survival rates dip down to around 16-30 percent with very few treatment options available.

In many cases, it’s the patient’s last shot.

That Hail Mary setting is part of what makes CAR-T therapies so impactful. In a 50-person Phase 2 trial, some 82 percent of patients infused with CTL019 engineered cells achieved either “complete remission” or “complete remission with incomplete blood count recovery” three months after the infusion.

“CTL019 represents progress toward helping children and young adults with r/r B-cell ALL, a patient population with an urgent need for new treatment options,” a Novartis spokeswoman stated via email.

CAR-T therapies center around an autologous transplant.

Blood is first drawn from the patient and then sent to a specialized facility. There, the T-cells in the blood are isolated, activated, and engineered ex vivo to express either a chimeric antigen receptor (CAR) or a T-cell receptor (TCR), depending on the cancer target. To amplify the effect, the T-cell population is multiplied, creating an army of tumor assassins to dose back into the patient.

If the therapy is successful, the CAR-Ts will seek out and destroy cancer cells throughout the body, distinguishing them from healthy cells by the antigens they express.

It’s a complex procedure that has proven fatal on multiple occasions. A similar program run by Juno Therapeutics was put on hold by the FDA late last year after a series of patient deaths were reported.

Juno’s setback left Novartis and Kite Pharma out in the lead. Based in Santa Monica, California, Kite has non-Hodgkin’s lymphoma in its cross-hairs. It too is eyeing a first quarter submission for its BLA, a company spokeswoman confirmed via email on March 29.

“We remain on track for completing our submission by the end of the month.”

There’s enough of a market for multiple players to get involved. But only one company will get to set the initial list price. Is that a curse, or a blessing?

With the sheer number of highly-involved components that go into a CAR-T immunotherapy, it has been hard to imagine the procedure becoming affordable and accessible for all eligible patients. As always, drug pricing is front-of-mind.

MedCity had the opportunity to ask Kite about its pricing plan in January at the J.P. Morgan Healthcare Conference. Chief Commerical Officer Shawn Tomasello took the question and (predictably) declined to give a definitive range. With education, however, she was confident the therapy would be covered.

What we do know is in regards to the stakeholders, whether it’s a patient, physician or a payer; the more they know about axi-cel, CAR-T, the potential transformation of the clinical results, the higher value they assign to the therapy. So right now we’re very focused on educating all the stakeholders. We’ve met with all of the commercial payors at least once, many of them twice. We’ve had two meetings now with CMS. And all indications are that axi-cel will be covered. They’re very excited. They understand the impact on member per month. Noone, noone in that environment has asked about pricing.

What is clear is that the healthcare world has never seen anything quite like this therapy before. Beyond pricing, there are many logistical quirks to iron out. Asked about the company’s commercialization efforts, a Novartis spokeswoman was vague.

“While it is too early to talk about our commercial model, receiving Priority Review designation underscores CTL019’s potential as a novel treatment innovation… And, with our manufacturing facility in Morris Plains we have a strong foundation for implementing the CTL019 manufacturing process and supporting clinical supply and approval timelines.”

The company’s pivotal phase 2 trial encompassed 25 centers in the U.S., E.U., Canada, Australia and Japan, which clearly bodes well.

Let’s hope Novartis can now spend some time brainstorming a solid brand name: CTL019/tisagenlecleucel-T doesn’t quite roll off the tongue.