Kite submits IND for CAR-T multiple myeloma treatment; Novartis keeping wary eye on rival’s latest move in high-stakes race.

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The News:

Kite Pharma Inc. (Santa Monica CA) said it has submitted to the FDA an Investigational New Drug (IND) application to launch a Phase 1, first-in-human trial of a chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA) in patients with relapsed/refractory multiple myeloma.

KITE-585 is designed to work through the engineering of a patient’s T cells to express a CAR that targets BCMA, a protein expressed on the cell surface of multiple myelomas, then redirecting those T cells to kill cancer cells, according to Genetic Engineering & Biotechnology News. KITE-585 contains a receptor derived from a fully human monoclonal antibody and a CD28 co-stimulatory domain intended for optimized T-cell expansion and function.

Kite disclosed its intent to advance KITE-585 into the clinic in April, when it presented preclinical data on the CAR-T therapy at the American Association of Cancer Research (AACR) Annual Meeting in Washington DC.

In one study–Abstract #4979, “Development of KITE-585: A fully human anti-BCMA CAR T-cell therapy for the treatment of multiple myeloma”—KITE-585 showed what the company termed potent activity against multiple myeloma (MM) cell lines, both in vitro and in vivo. CAR-T cells were active in the presence of soluble BCMA and also eradicated established multiple myeloma tumors in mice.

In a poster presentation at AACR—Abstract #2135, “Selectivity and specificity of engineered T cells expressing KITE-585, a chimeric antigen receptor targeting B-cell maturation antigen (BCMA)”–KITE-585 showed specificity for BCMA-expressing target cells due to the selectivity of its novel single-chain variable fragment (scFv) for BCMA, following an assessment using Retrogenix™ cell microarray technology.

KITE-585 is Kite’s third CAR-T cancer immunotherapy candidate to advance into the clinic and beyond. The company in March completed its Biologics License Application seeking FDA approval for its lead CAR-T product axicabtagene ciloleucel (formerly KTE-C19) in relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) who are ineligible for autologous stem cell transplant (ASCT).

“KITE-585 has the potential to become Kite’s next significant advance in cell therapy for patients with cancer,” David Chang, MD, PhD, Kite’s EVP of R&D and CMO, said in a statement.

Kite and Novartis AG (Basel CHE) have emerged as leading developers of CAR-T cancer immunotherapies, with both seeking the first FDA approval of a CAR-T treatment. Last month, Novartis won an FDA advisory committee’s unanimous recommendation of approval for Novartis’s leukemia-fighting treatment CTL019 (tisagenlecleucel), a CAR-T therapy developed through a collaboration between the pharma giant and researchers from the University of Pennsylvania launched in 2012.

CTL019 is indicated for the treatment of relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL).

Steve’s Take:

Ladies and gentlemen: Start your CART-T marketing and sales engines. Oh, you’re already years out of the blocks. How’d that happen without hardly anybody noticing?

The news about Kite’s IND filing was just another sign it’s not waiting for some Big Pharma to put multiple billions on the table either for its portfolio of current CAR-T treatments or the whole corporate enchilada.

Far more importantly for investors, the FDA has ev­i­dently learned all it wants at this point from its out­side on­col­ogy ex­perts on CAR-T, reports John Carroll for Endpoints. Kite Pharma’s closely-watched CAR-T drug axi-cel is get­ting a pass on a meeting of the oncologic drugs advisory committee, which may sig­nal a quick thumbs-up from reg­u­la­tors. Kite execs think so, say­ing that they will be fully launch-ready by Sep­tem­ber in case an early green light comes through.

In a 2Q call with an­a­lysts Tues­day morn­ing, Kite R&D chief David Chang told an­a­lysts the FDA had no­ti­fied the biotech that reg­u­la­tors will not be or­ga­niz­ing a panel re­view with out­side ex­perts for axi-cel. No­var­tis was first up in July, gain­ing unan­i­mous back­ing for CTL019 from an FDA panel in the prelude to an early-Oc­to­ber PDUFA date.

No­var­tis had been seen as the clear front-run­ner in the race to get into the mar­ket first, but with the FDA fin­ish line hazy at best, and obscure at the very least, both they and Kite may now both launch al­most si­mul­ta­ne­ously. Tt could actually happen.

“We are ex­tremely en­cour­aged by the re­cent ad­vi­sory com­mit­tee meet­ing” for No­var­tis, Chang said, which he views from the faith-based position as a positive har­bin­ger for Kite. “The FDA has in­formed us that they will not sched­ule an ad­vi­sory com­mit­tee meet­ing” for axi-cel.

This fol­lows an FDA in­spec­tion of its man­u­fac­tur­ing fa­cil­ity and its treat­ment cen­ters in the lead-up to an ac­cel­er­ated re­view and final de­ci­sion.

Kite faces a No­vem­ber 29 dead­line for its mar­ket­ing de­ci­sion from the FDA, but the com­pany says it’s ready to start mak­ing the per­son­al­ized ther­apy and start ship­ping al­most im­me­di­ately.

These pi­o­neer­ing CAR-T drugs offer a golden generation to the ap­proach in treat­ing blood can­cers. T cells are ex­tracted from pa­tients and armed with chimeric anti­gen re­cep­tors, turn­ing them into can­cer fight­ers that are pumped into a po­tent mix that is then in­fused into the pa­tient.

Kite’s Axi-cel is widely viewed as a block­buster in the mak­ing, and Kite has been build­ing man­u­fac­tur­ing op­er­a­tions and a com­mer­cial group with plans to hit the ground run­ning, scoring a vein-to-vein turn­around time on this ther­apy of 17 days. In the mean­time, its R&D group just sig­naled that they have filed for an IND to start Phase I work on KITE-585, its next-gen ap­proach that tar­gets BCMA.

“With the an­tic­i­pated events on the hori­zon for the re­main­der of 2017,” said CEO Arie Bellde­grun, “the po­ten­tial for CAR-T to be­come one of the most pow­er­ful anti-can­cer agents for cer­tain pa­tients may fi­nally be re­al­ized.”

Bottom Line:

All the excitement over CAR-T is duly earned and well deserved. Now that the clinical data are pouring in, I might add something from a personal experience. A neighborhood MD friend was diagnosed out of the blue with multiple myeloma and underwent the experimental Kite CAR-T treatment. He’s now feeling much and is back at the work he loves, viz., caring for people. Out of the woods entirely? Not yet. But hopeful? Hell yes.

Problem is that the cost, which was picked up by both Medicare and his hospital employer, ran to around $650,000. And that’s the “bargain” price. Treatments in this category of one-dose “cures” start here and go up to $1M+.

That begs the question of who will get the treatments, and the answer is? The payers will decide.

Drug costs are spiraling upwards and so too are frustration levels. Payers with stretched budgets are still struggling to make the case for “big ticket” drugs. Meanwhile, Pharma is eager to prove that higher-cost drugs are justified and will ultimately save money. But are payers listening? And just how convinced are payers by Real World Data (RWD)? Is the evidence being provided matching their needs–or is it missing the point?

The actual answer to who gets access to these extremely costly “wonder drugs” relies on the payer. That’s because an insurance company will not pay for a new therapy unless it is proven that CAR-T therapy, for example, works and is a cure, by their standards not just the FDA’s, it is safe, and it saves the insurance company money.

But in order to ascertain this, economic data must be collected for a predetermined period of time not just to demonstrate these factors, but also that the med saves the company money compared to “standard of care” treatment. This can be generic versions of the drug or biosimilar of a biologic drug.

If the insurance company will not cover the ultra-expensive, single-dose therapy, then the patient or family will have to pay for it. Most patients and families cannot afford these potential cures and they instead will be forced to rely upon the standard treatment(s) and cross their fingers.

Steve's Take: To fulfill the promise of CAR-T therapy, they must be covered by #health insurance Click To Tweet

These new therapies should be covered by insurance. When donor CAR-T cells from another person are demonstrated to work as well as the patient’s own CAR-T cells, the cost of therapy will almost certainly decrease appreciably.

What has the market said about these two companies’ shares?

Novartis is up 14% this year, while Kite has rocketed 269%. Analysts who cover Novartis have a median 12-month price target of $90.50–up 9% from its closing price Aug. 10. The median price target for Kite is $88–27% below its closing price.

Steve Walker has no position in any stocks mentioned. MedContent Inc. has no position in any stocks mentioned. MondayMorning.com has a disclosure policy.