To Be More Than Quick Splash, Gilead’s CAR-T Purchase Faces Hurdles

Xconomy San Francisco — 

[Updated 8/28/17, 6:45p.m. ET. See below.] Gilead Sciences CEO John Milligan promised today that the company’s $11.9 billion acquisition of Kite Pharma and its cutting-edge CAR-T cell therapy would not be a “one and done” proposition. “This is a long-term play with multiple product opportunities,” Milligan said, calling it the foundation of Gilead’s “fairly nascent” cancer business.

Unless drug regulators make a shocking turn in coming months, Gilead (NASDAQ: GILD) should have an historic approval to mark its acquisition. By Nov. 29, the FDA will decide whether to approve Kite’s (NASDAQ: KITE) first CAR-T cell therapy product, axicabtagene ciloleucel, or axi-cel, as a treatment for the most desperate cases of non-Hodgkin lymphoma. Because of the high rate of remission and manageable side effects in Kite’s clinical studies, an FDA rejection would be a major surprise.

Beyond that, however, Kite’s prospects—and those of the CAR-T field more generally—become much more speculative. Kite, which will operate as a division of Gilead, must navigate a minefield of technical and biological problems while outpacing well-heeled competitors. The deal prompted plenty of skepticism among public investors. In a Mizuho Securities survey of 112 investors, 59 percent of respondents said Gilead overpaid for Kite. [The results of the Mizuho survey have been updated.]

The price tag, at $180 a share, is a 29 percent premium to Kite’s closing share price Friday. While Gilead wants to expand axi-cel to NHL patients with less advanced disease and other blood-borne cancers, the company says the business from the first indication—relapsed or refractory NHL—in large part should make the deal “revenue neutral” within three years, Milligan said. “The vast majority of our valuation” for the deal comes from axi-cel, he said.

The premium is somewhat deceptive. Kite stock was already up 210 percent in 2017, which makes Gilead’s willingness to pay more “bracing,” wrote Leerink analyst Geoffrey Porges in a research note Monday, “and suggests that Gilead is expecting [annual] revenue of $2 to 3 billion from Kite’s CAR-T platform in the future.”

Gilead officials today did not make sales projections for axi-cel; in the Mizuho survey, respondents estimated peak axi-cel revenue, on average, at $1.6 billion a year.

One prominent owner of Kite stock gave his thumbs-up. “We are happy shareholders today and are grateful for all that Kite has accomplished for patients who will benefit from CAR-T,” wrote Brad Loncar in a note. Loncar runs an investment fund dedicated to cancer immunotherapy. The fund index (NASDAQ: CNCR) climbed more than 6 percent Monday with the Kite deal news. Kite shares closed Monday 28 percent higher, at $178.05. Gilead shares climbed 90 cents to $74.69.

Analyst forecasts of future revenues can be notoriously off. And there are all kinds of open-ended questions about CAR-T, which has no approved products yet. Patient deaths due to extreme brain swelling last year scuttled a CAR-T to treat a form of adult leukemia, which was the lead product from Juno Therapeutics (NASDAQ: ticker:JUNO]]) at the time. A death from the same condition occurred in Kite’s key NHL trial but has not derailed axi-cel’s progress.

Juno cofounder and investor Bob Nelsen of Arch Venture Partners cheered the Gilead-Kite news today on Twitter. Juno wants to push its own CAR-T therapy for NHL into late-stage studies.

High prices and complex manufacturing could dampen demand for axi-cel, if approved. “The true inflection points in the Kite story are yet to come,” wrote Evercore ISI analyst Umer Raffat in a research note.

On a conference call today, Milligan and other executives pointed repeatedly to an upcoming Kite study, called Zuma-7, which will compare axi-cel to bone marrow transplant in patients with less severe cases of NHL. That comparison, for Kite and others developing CAR-T products, is a key consideration for the field. CAR-T’s side effects are generally manageable and tolerable when the patient has no other treatment options. But to replace bone marrow transplant—the standard of care and sometimes a cure—in earlier instances of disease, Gilead’s Milligan acknowledged, axi-cel would have to prove itself safe enough in larger studies.

Only then could companies possibly justify sky-high prices for their products. If they merely serve more as a “bridge” to get patients ready for transplants, CAR-T companies would have to lower their sightlines. For autologous CAR-T like Kite’s—meaning the therapy involves a complicated process that extracts a patient’s own T cells, engineers them outside the body, and ships them back to the patient for infusion—analysts have floated possible prices in the hundreds of thousands of dollars, the same range as the most expensive rare disease treatments.

“This innovation will support healthy reimbursement,” said chief operating officer Kevin Young.

In late 2015, a British academic group mocked up theoretical U.K. pricing models for CAR-T treatments. CAR-T used as a bridge to prepare patients for a bone-marrow transplant was considered less valuable than CAR-T standing alone as a potential cure. With many caveats, the group estimated rough costs of each north of a half-million dollars per patient.

Another blood cancer hurdle for Kite is the disease multiple myeloma, the third deadliest blood cancer in the U.S. Kite has a product, but unlike competitors including myeloma therapy leader Celgene (NASDAQ: CELG) via its alliance with Bluebird Bio (NASDAQ: BLUE), it has yet to report any clinical data.

Beyond blood cancers are much more prevalent solid tumors, such as those in breast, lung, and colon cancer. There are no data yet to suggest CAR-T therapies can treat solid tumors, which have sophisticated defenses against T-cell attackers, but Gilead executives expressed confidence that Kite’s platform would eventually pay off there, too. (For solid tumors, Kite is working on cell therapies that are, in effect, close CAR-T cousins. They are engineered to attack targets inside tumor cells instead of on the tumor surface.)

While CAR-T therapies have notched remarkable gains in a few short years of lavish funding, those gains have been in very limited groups of patients. Ultimately, as with other new types of cancer treatments that stimulate the immune system, the future of the field is likely combinations of drugs that attack tumors from different angles.

Explorations into CAR-T combinations have barely begun. Kite should give Gilead some insight there: Kite has one study underway, partnering axi-cel with a Genentech antibody drug. Unlike Merck, Bristol-Myers Squibb, Genentech’s parent Roche, and other cancer drug heavyweights, Gilead has very little in its own portfolio to combine with. But Gilead has plenty more to spend; the money it is paying for Kite is not even one-third of the $37 billion, as of June 30, it has on hand. While Gilead might not spend any more on CAR-T companies, wrote Leerink’s Porges, the deal “does not preclude [the company] from making further investments in other cancer treatment platforms.”

Image of human lymphoma tumor cells via the National Cancer Institute.