The cost watchdog ICER will bless some high-priced gene and cell therapies, but only with solid proof of benefit: Analyst


On the surface, it may seem that the higher the price of a new drug, the harder it is for its developer to get a thumbs up from the Institute for Clinical and Economic Review (ICER). For companies in the fast-growing area of ​​gene and cell therapy, this would make the ICER review a difficult hurdle, especially if the agency’s opinions gain more weight in the future when deciding on insurance coverage.

However, Mizuho Securities analysts have looked at most of the ICER’s previous judgments on gene and cell therapies and identified a surprising trend: the institute’s reviewers rated more than half of the products tested to date as inexpensive. And the evidence they used to reach these positive conclusions provides important research, development, and pricing lessons for next-generation gene and cell therapy developers, said analyst Difei Yang, Ph.D., lead author of two reports that Mizuho sent customers in an interview last week.

“Of course they pay attention to the time that the patient gains, but also to the quality of life,” said Yang. Companies struggling to provide robust data showing that gene or cell therapy could outperform standard of care for either treatment – direct studies, solid evidence of long-term benefit, etc. – were more likely to receive a positive ICER judgment Economy, thought Mizuho.

Manufacturers of CAR-T cancer cell therapies have so far been much more successful in proving superiority over the standard of care than manufacturers of gene therapies for rare diseases, Mizuho noted. ICER confirmed the cost effectiveness of the first two CAR-Ts on the market, Gilead’s Yescarta for lymphoma and Novartis’ Kymriah for lymphoma and leukemia, both approved in 2017 and retailed for $ 373,000 and $ 475,000, respectively. And the agency has already announced that it will give the thumbs up to the previously unapproved CAR-T-Cilta-Cel with multiple myeloma from Janssen and Legend Biotech – assuming it costs $ 475,000 or less.

Only one in four CAR-Ts that ICER reviewed failed to meet the cost-benefit line: Bristol Myers Squibbs Ide-Cel for multiple myeloma, that was started this spring with the brand name Abecma priced at $ 419,500. A spokesman for BMS complained at the time that ICER relied on “inadequate modeling of overall survival data from ide-cel and a misguided view of re-treatment”.

ICER President Steve Pearson, MD, quoted “Major evidence gaps” in the data available to the agency while reviewing the cost-effectiveness of multiple myeloma treatments.

Pearson said in an interview that ICER reviewers sometimes struggle to determine how to translate data from often brief studies into real results. “We need to see longer-term data that we can relate to what we see in the short-term,” Pearson said. “What we really want to see are patient-relevant results, such as their functionality and their quality of life.”

Companies are often inadequate when it comes to providing data that clearly contrasts patients who receive gene or cell therapies and those who don’t, Pearson said. “You say maybe [non-treated] Patients only have six months to live, but sometimes the comparison just isn’t that clear, ”he said. “[Or] the [standard-of-care] Data can be 10 years old. We know that care will change over 10 years. “

BMS took a step in this direction with another CAR-T in its portfolio, Breyanzi, which was approved for large B-cell lymphoma in February. The trial version was released last week Data showed an improvement in event-free survival in patients receiving CAR-T treatment compared to those treated with Roche’s gold standard Rituxan, high-dose chemotherapy, and stem cell transplantation.

It’s too early to define Breyanzi’s ability to prolong life, but BMS hopes the data will ultimately move the CAR-T earlier in the treatment plan and differentiate the product from lymphoma rivals Yescarta and Kymriah. Breyanzi was introduced at a list price of $ 410,300. ICER has not yet reviewed the product.

Yang von Mizuho says the opportunity to get the green light for earlier treatment could motivate such head-to-head studies, and ultimately, those data would likely bring ICER on board with high-priced cell and gene therapies as well. “The sooner you treat the patient, the better off he is. And the better they are, the lower the net cost to the health system, ”she says.

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On the other hand, gene therapies from ICER have received mixed ratings for cost-effectiveness. Take Spark Therapeutics’ Luxturna, which is approved for a rare hereditary condition that causes blindness in people one year and older. ICER determined that the product that started at $ 850,000, it would be cost-effective if it were given to patients aged three years, but not if given to patients aged 15 or later, since by then they would have lost a significant amount of their vision.

Yang attributed the verdict to the cost of nursing care. “ICER tries to quantify how much a caregiver costs. So if the child is treated earlier, the idea would be that they are more independent and require less care, ”says Yang. “By the time they are treated at 15, much of that cost has already been incurred. And this message is in line with gene therapy in general. “

However, Pearson said ICER’s reviewers placed more emphasis on the overall value of preventing blindness to society. “There really are no health costs to speak of when you’re blind,” he said. “But society saves money to some extent because training costs are lower, patients have full career opportunities and higher earning potential when they see fully.”

ICER initially resisted Novartis’ $ 2.1 million gene therapy for spinal muscular atrophy (SMA), Zolgensma, but also refused to approve Biogen’s SMA drug Spinraza. Spinraza kicked off at up to $ 750,000 each year thereafter for the first year and a half, which eventually led ICER to determine Zolgensma is the lesser of two evils in terms of cost.

BioMarin’s Roctavian, a haemophilia gene therapy, cleared some hurdles on the road to approval, but ICER has already determined how it would be cost-effective. At a wildcard price of $ 2.5 million, ICER estimates that if gene therapy lasted for a dozen years, it would save the healthcare system about $ 5 million per patient compared to chronically dosed factor VIII. “This is an example of where gene therapy can really be doomed [costs]”Said Yang.

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After looking into ICER’s methodology, Yang said she had a bone to choose with the agency. “Right now, their judgments are based on clinical evaluation, but the value of innovation should be considered in some way,” she said. “We learn something in the process, and it has to be permanent. I don’t think that will be recorded. “

Pearson’s answer? “We are sensitive to the idea that treatments with different approaches are useful, but we don’t see innovation as something separate from the benefits to patients and families,” he said. “Innovation is important to patients in that it helps them lead better lives. If it’s not better for the patients, I’m not sure we should pay more for it. “

ICER recently stepped up efforts to maintain an ongoing dialogue with biopharmaceutical developers and insurance companies. The agency has adopted a “formal 12-month checkup” policy for each of its published reports, Pearson said. If new data was released during this time, the reviewers can reconsider their original judgment.

It also introduced ICER Analytics, a cloud-based portal that houses all of its economic models. Life science companies and insurers can subscribe to ICER Analytics. “If [a drugmaker] Has new evidence or if they disagreed with our assumptions the first time, they can fill in their own information and get a different result at a fair price, ”Pearson said. “We’re going to put this together with our original results for payers to see.” More than 50 companies have signed up for trial subscriptions since ICER Analytics launched in November, he said.

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