資料來源：https://www.bloomberg.com/news/articles/2017-01-30/novartis-signals-growing-ambitions-for-car-t-cancer-treatments

Novartis AG is pushing ahead with one of its most ambitious cancer therapies, a treatment that the Swiss drugmaker has said has blockbuster potential as it extends that technology to a wider pool of tumor-ridden patients.

Europe’s second-biggest drugmaker is planning to test its CAR-T treatments — which involve extracting immune cells and genetically engineering them to hunt and kill cancer cells before returning them to the patient’s body — on lethal cancers of the brain, pancreas, colon, ovary and lung.

The company has also doubled its investment in manufacturing for these treatments.

The efforts put Novartis in a race with Juno Therapeutics Inc, Kite Pharma Inc and Bluebird Bio Inc to master the technology, part of a class of therapies that harness the body’s defense system to attack tumors.

Novartis’ initial target is an acute form of leukemia in children, and it expects to seek approval from the US Food and Drug Administration (FDA) early this year.

Analysts have estimated the therapy, CTL019, will cross US$1 billion in annual sales in five years.

“This could be the most efficacious immune therapy as yet developed, and it’s just early days with this technology,” Novartis Institutes for BioMedical Research president Jay Bradner said in an interview at the company’s headquarters in Basel, Switzerland.

Novartis is trying to catch up to rivals including Merck & Co and Roche Holding AG in cancer immunotherapies.

The company, which last year invested about US$9 billion in research and development, has more than 30 cancer assets under development and is “investing massively” in immuno-oncology, Novartis oncology chief executive Bruno Strigini said.

Still, questions arose about Novartis’ commitment to CAR-T research after the drugmaker said in August last year that the work would no longer be housed in a separate division, a restructuring that included cutting 120 jobs.

The CAR-T sector itself has faced its share of skeptics: Use of the treatments beyond certain blood cancers and the feasibility of large-scale manufacturing of such personalized cancer therapies are yet to be proven. And while the experimental treatments have shown dramatic results, they have also led to severe side effects, and in some cases death.

Novartis is confident about the balance between the safety and efficacy of its therapies, Strigini said. The next step would be to seek approval for the use of its CAR-T therapies in patients with diffuse large B-cell lymphoma, a type of blood cancer that afflicts a larger group of people.

That is likely to happen by the end of this year, he said.

Beyond that, Novartis, working with the University of Pennsylvania, is also exploring using its treatments on so-called solid tumors, said Glenn Dranoff, who leads immuno-oncology efforts at the Novartis Institutes.

CAR-T therapy has been shown to work against cancers in the blood, but has yet to be proven against solid tumors, or cancers that occur in bones, muscle and organs.

There is no doubt that treating solid tumors with CAR-T cells will be more challenging, partly because T cells have to make a bigger effort to get into the tumor from the blood, said Marcela Maus, director of cellular immunotherapy at Massachusetts General Hospital’s cancer center.

And there may be better approaches, she added.

“T-cell therapies are a new platform — the trick now will be extending it to more cancers and having a better understanding of how and which patients can benefit the most,” Maus said.

Competitors are also seeing signs of success.

Kite in December last year said it was seeking FDA approval for its CAR-T therapy in a type of lymphoma.

The same month, Juno said most patients with a form of blood cancer responded to its experimental treatment with manageable side effects, which might help invigorate the company after a different trial was halted due to patient deaths.

Bradner, who joined Novartis a year ago from Harvard Medical School and the Dana-Farber Cancer Institute, said the company does not expect any regulatory surprises for its therapy based on discussions so far.

More than 80 percent of patients went into remission in a mid-stage study published in December evaluating its CAR-T therapy in children and young adults with acute lymphoblastic leukemia, a fast-growing disease, he said.

Some patients are likely to be free of the disease for five years or more following treatment with CAR-T, Bradner added.

“It’s tantalizingly close to ‘cure,’ though it’s hard to know with certainty when that happens or how frequently patients will have a long interval where they can feel and be cancer free,” Maus said.