Onco-Immunology Companies like Juno, Novartis AG, Kite Pharma Struggle to Mass Produce Custom Cancer Therapies

October 30, 2015
By Mark Terry, BioSpace.com Breaking News Staff

As the newest and hottest type of drug treatment, onco-immunology, starts to enter the market, companies like Novartis, Juno Therapeutics and Kite Pharma are grappling a profitable manufacturing process.

At its broadest, onco-immunology involves taking specific molecules that identify a specific tumor, and programming the patient’s immune system to specifically attack those cells. From a practical point of view, it requires taking cancer cells and white blood cells out of the body, identifying specific cancer cell markers, and programming the white blood cells to identify them. They are then reintroduced into the patient’s body, and the programmed cells will attack the cancer cells.

In particular, companies are working with checkpoint inhibitors, which are molecules that cancer cells produce that shut off the immune system, and immune cell stimulators. Checkpoint inhibitors are molecules produced by tumor cells that stop the immune cells from attacking the cancer cells. A great deal of work has been done on checkpoint inhibitors that block PD-1, and CAR T therapies.

Companies working in this area include CytomX Therapeutics, Bristol-Myers Squibb, Merck, Corvus Pharma, Amgen, Celgene and many, many others

CAR T therapies appear to be particularly effective for leukemia and other blood cancers, with some researchers going so far as to call them cures. Studies have shown these treatments to eliminate all evidence of leukemia and lymphoma in anywhere from 40 percent to 90 percent of patients.

But they come with a steep price, with some expected to hit $450,000 for a treatment.

“CAR T cell treatments are one of the great advances in cancer therapy in the last decade,” said James Ferrara, head of hematological cancer research at Mount Sinai Hospital in New York to Reuters. “In patients that have been unresponsive to the most effective therapies we have, including bone marrow transplants, leukemia seems to completely disappear.”

With a treatment that is enormously successful — even curative — one would think the products’ success would be a given, despite the costs. But history has suggested it’s not always the case. Seattle-based Dendreon was one of the leaders in the area with a treatment called Provenge (sipuleucel-T), an immuno-oncology treatment for asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. Dendreon required white blood cells be removed from the body, be mixed with the vaccine, and infused back into the patient. In November 2014, Dendreon declared bankruptcy. In February of this year, Valeant acquired the company’s assets.

Provenge never really took off. It’s treatment cost $93,000, was very labor intensive, and apparently only showed a four-month improvement in median survival rate. And to be fair to Dendreon, CAR T therapies appear to be more effective in blood cancers than in solid tumors.

In 2013, Novartis acquired Dendreon’s CAR T cell production facility in New Jersey. “We feel confident we can scale up to thousands of patients a year with a true global facility,” Usman Azam, head of Novartis’ cell and gene therapies, told Reuters. That would likely be enough for the first couple years of treatment demand and if necessary, a second plant would be built, according to Azam.

Novartis’s treatment, CTL019, is, according to Azam, “potentially curative.”

Novartis is planning to apply for approvals with the FDA for CTL019 in 2016 in children with acute lymphoblastic leukemia (ALL). And in 2017, if all goes well, apply for use of the treatment in non-Hodgkins lymphoma, specifically diffuse large B-cell lymphoma (DLBCL).

Kite Pharma, Inc. and Juno are also retooling their production facilities. Meanwhile, they are utilizing contract manufacturers to make the experimental cells being used in clinical trials. Kite indicates it should be able to process enough CAR T cells for 5,000 patients annually.

“That should cover the initial launch of KTE-C19 and maybe the first two to three years afterward,” said David Chang, Kite’s chief medical officer to Reuters.

Pricing will still be a factor, with these new therapies likely to make Provenge’s $93,000 price tag look like pocket change, with analysts suspecting pricing could hit $200,000 to $300,000 per treatment.

“If their therapies cost $50,000 to $150,000 to make, clearly they’d need to have a $250,000 to $450,000 price point,” Wedbush Securities analyst David Nierengarten told Reuters.

James Kuo, an analyst with Northland Capital Markets, agrees. He told Reuters that Juno’s treatment would likely be priced at $300,000 for initial treatment for adult ALL, if approved. And that, he indicated, would assume a $45,000 cost per patient for manufacturing.

Juno’s Hans Bishop, the company’s chief executive officer, indicates the price will depend on how well the company’s JCAR015 does in larger clinical trials, noting that in an earlier trial in adults with aggressive ALL, 89 percent had complete remissions.

Other companies are looking at a different approach, using healthy immune cells and programming them for broader cancer markers. Although this would be easier to scale, it runs into problems of immuno-rejection, as well as less sensitivity to an individual’s specific cancer type. One company working in this area is France-based Cellectis. They’re likely a decade from a marketable technology, however. But if Cellectis could pull it off, it could be an enormous success.

“If it plays out, it would be a game-changer of a company,” said Behzad Aghazadeh, a managing partner at venBio to Reuters. “Any reasonable person would say, ‘I’ll take the off the shelf product.’”