Novartis gets FDA nod for breakthrough leukemia treatment Kymriah; with a cost of $450,000, who’s going to get it?

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The News:

Novartis AG (Basel CHE) has obtained approval from the US Food and Drug Administration (FDA) for its Kymriah (tisagenlecleucel or CTL019) to treat children and young adults with B-cell precursor acute lymphoblastic leukemia (ALL). The approval extends to patients up to 25 years of age with B-cell precursor ALL, which is refractory or in second or later relapse, according to Regulatory Affairs.

Kymriah is the chimeric antigen receptor T cell (CAR-T) therapy and one-time treatment that uses a patient’s own T cells to treat cancer. According to the company, Kymriah is the first therapy based on gene transfer approved by the FDA. In 2012, Novartis collaborated with the University of Pennsylvania to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.

Novartis will use its New Jersey facility to manufacture Kymriah for each individual by using their own cells. The approval was based on data from the pivotal open-label, multicenter and single-arm Phase 2 ELIANA trial. ELIANA is said to be the first pediatric global CAR-T cell therapy registration trial, which evaluated patients in 25 centers in the US, EU, Canada, Australia and Japan.

In April, Novartis obtained FDA “breakthrough” therapy status for CTL019 based on data from its JULIET study, which is the multi-center global registration study for CTL019 in adult patients with relapsed-refractory diffuse large B-cell lymphoma (r/r DLBCL).

Novartis CEO Joe Jimenez said: “Five years ago, we began collaborating with the University of Pennsylvania and invested in further developing and bringing what we believed would be a paradigm-changing immunocellular therapy to cancer patients in dire need. He added, “With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care.”

Steve’s Take:

The very beneficial, exciting news is that the FDA approved a revolutionary new approach to treating cancer, clearing a Novartis therapy that has produced unprecedented results in patients with a rare and deadly cancer. The quandary, though, is the price, viz., $475,000 for a course of treatment.

That sounds astonishing to many patients–but it’s far less than analysts expected and payers are mulling over who will access the treatment and who won’t.

The therapy is leading a pack of novel treatments that promise to change the standard of care for certain aggressive blood cancers, STAT reports.

The treatment’s approval looked a slam dunk for months, but its potential price has been the subject of speculation and debate. Novartis picked the $475,000 price tag in an effort to balance patient access to Kymriah while giving the company a return on its investment, said Bruno Strigini, Novartis’s head of oncology.

The cost is below Wall Street analyst expectations, which reached as high as $750,000 for a dose. And it’s considerably cheaper than the roughly $700,000 price tag that UK regulators said would be fair, considering Kymriah’s potentially life-saving benefits.

Novartis also said it’s working with Medicare on a system in which the government would only pay for CAR-T treatment if patients respond within a month.

In a clinical trial, a single dose of Kymriah left 83% of participants cancer-free after three months, results oncologists have hailed as a major advance for patients with few other options. The most frequent side effect was an inflammatory storm called cytokine release syndrome, a reaction to CAR-T that can prove fatal in some patients but is commonly controlled with immunosuppressant drugs.

“I think this is most exciting thing I’ve seen in my lifetime,” said Dr. Tim Cripe, an oncologist with Nationwide Children’s Hospital, at an FDA meeting on Kymriah in July.

Unlike well-understood pills and commonly injected biotech drugs, CAR-T presents a profound, new model for doctors, regulators, and payers. Each dose is custom-tailored for an individual patient, requiring a complex process in which human cells must be safely transported across the country, reliably re-engineered, and carefully returned.

That creates logistical issues unseen with previous drugs. To get Kymriah, patients will have to travel to one of just 32 sites around the country, STAT points out. From there, doctors harvest patients’ white blood cells and ship them off to a Novartis facility in New Jersey where they can be edited and mailed back.

The entire process takes about 22 days, the company said. And the $450,000 price tag covers only Novartis’s role, not the costs of travel, hospitalization, or any drugs needed to tamp down Kymriah’s side effects.

Steve's Take: It remains uncertain just how profitable a business opportunity #Kymriah presents? Click To Tweet

And it remains uncertain just how profitable a business opportunity Kymriah presents. There are about 3,100 new cases of ALL each year, but roughly 70% can be induced into remission by standard therapy. That could leave just a few hundred patients who might be eligible for Novartis’s therapy, casting doubt on whether the company can get an gigantic return on what will be a substantial manufacturing investment.

But CAR-T’s potential goes far beyond Wednesday’s approval.

Novartis is developing Kymriah for use in lymphoma, and its pipeline includes other CAR-T therapies targeting an array of blood cancers. Kite Pharma Inc. (Santa Monica CA), soon to be acquired by Gilead Sciences Inc. (Foster City CA), is awaiting FDA approval for a lymphoma therapy and is, like Novartis, developing a multitude of cell therapies it hopes can treat tumors liquid and solid. Juno Therapeutics Inc. (Seattle WA), which slipped into a third place after its lead CAR-T ran into safety problems, has a similar focus.

Bottom Line:

In the past, drug development was mostly focused on small molecules where chemical pathways were well known and where a chemical reaction will occur in the same manner whether the first time or another time, notes Regina Au at BioMarketing Insight.

Then the industry moved into biologics or large molecule where the biology is more complicated, and one cannot predict how a cell is going to react each time. Large molecule drug discovery, therefore, is inherently more expensive and scientists also had to figure out a way to get these large molecules to the right target.

For payers to determine whether a particular CAR-T therapy saves them money, economic data must be collected for a predetermined period 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.

In the past I’ve written that 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.

To prevent healthcare costs from mushrooming out of control, we need to alter the national mindset such that everyone unconsciously practices preventive care, takes responsibility for their own health, embraces the notion of treating the right patient with the right drug, with the freedom of advance technology being covered by insurance.

One thing seems clear. The growing number of heretofore untreatable diseases is swelling—-a very good thing, to be sure. But it’s also placing increasing pressure on our national resources. The current situation of burgeoning big-ticket drug development is simply not sustainable. Workable positions that address this dilemma fairly for all citizens are needed now.

Regrettably, I don’t see the needed insights and answers coming from this White House.