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Why the FDA is making a test case of a cancer drug from China

At a quick glance, the Food and Drug Administration’s decision to ask its advisers for help in vetting yet another cancer immunotherapy may seem odd.

After all, the agency has already cleared seven drugs that work like the one it’s now reviewing. Known as sintilimab and developed by Eli Lilly and partner Innovent Biologics, the immunotherapy blocks a protein called PD-1, the same as Merck & Co.’s Keytruda and Bristol Myers Squibb’s Opdivo. Typically, the FDA reserves its advisory committee meetings for tough decisions on which it wants help from outside experts.

Yet on Thursday, a panel of agency advisers will convene to debate sintilimab and whether the data behind it are sufficient.

Lilly’s application has become a test of the regulator’s views on cancer treatments developed and tested exclusively in China. A handful of companies are using that blueprint in an attempt to speed new therapies to the U.S. market, raising concerns from some of the agency’s top cancer drug evaluators.

The drugs could also usher in greater price competition in a market filled with products costing well over $100,000 a year. Jacob Van Naarden, head of Lilly’s cancer drug business, hinted at this approach on a conference call last week, alluding to the company’s plans for “disruptive pricing.”

On Tuesday, the FDA posted briefing documents for the Thursday meeting that showed its staff to be highly skeptical of Lilly’s and Innovent’s drug. Here is an overview of the issues at stake, as well the potential implications of the FDA’s forthcoming decision.

What is sintilimab?

Sintilimab was discovered by Innovent, a biotech based in Suzhou, China. As a checkpoint inhibitor like Keytruda and Opdivo, sintilimab could have considerable value. These types of drugs have become standard treatment for many tumor types and are viewed as the backbone of future drug combinations. Nearly every large drugmaker invested in oncology has sought to have one, among them Lilly, a latecomer to cancer immunotherapy.

Lilly partnered with Innovent in 2015. Since then, Innovent has won approval of sintilimab in China, where it is sold as Tyvyt for a type of lymphoma. That clearance encouraged Lilly to broaden its alliance with Innovent in 2020 and test sintilimab in several tumor types, including lung cancer, one of the most common cancer types in the U.S. and a target for many drugmakers.

What results are supporting Lilly and Innovent’s application?

The application currently under review is for use of sintilimab alongside standard chemotherapy in patients recently diagnosed with advanced non-small cell lung cancer, the disease’s most common form. A combination of Keytruda and chemo is currently the standard of care for most patients, after a Phase 3 study showed in 2018 that treatment cut the risk of cancer progression or death by nearly half compared to chemo alone. Multiple other drug combinations are available as well.

Lilly and Innovent have recreated a similar result in a roughly 400-patient late-stage study called ORIENT-11. A regimen of sintilimab and chemo bested chemo on measures of survival and disease progression, leading the partners to seek approval in the U.S. But the study was run entirely in China and chemotherapy is no longer the bar to clear in lung cancer, two factors that appear to be influencing the FDA’s thinking. The agency is expected to make a decision by March.

What do Lilly and Innovent aim to offer with their drug?

Lilly is attempting to position sintilimab as a comparable, lower-cost alternative to Keytruda, a product profile that, in theory at least, could drum up some demand. High cancer drug prices can leave patients with substantial out-of-pocket costs, particularly when they must take several in combination. Such “financial toxicity” has become an increasing concern as more and more new products reach market with annual list prices of over $100,000 or even $150,000.

Immunotherapies are a chief culprit and could continue to be for years. Keytruda, for example, generated more than $17 billion in sales in 2021. Biosimilar competitors to Keytruda, Opdivo and other similar drugs, meanwhile, aren’t expected until later this decade.

At an industry meeting three years ago, the FDA’s oncology chief, Richard Pazdur, appeared to suggest competition from China was a way to lower prices. Pazdur even laid out a regulatory strategy for prospective checkpoint blockers from China that involved, for instance, mimicking the trials Merck ran for Keytruda in lung cancer.

Why is the FDA paying such close attention to this application?

Several trends in cancer drug development are converging in this review. With seven similar drugs already approved and more on the way, pharma companies have been criticized for taking a “me-too” approach when research dollars might be better spent on cancer medicines that work in new ways.

Furthermore, the FDA is increasingly scrutinizing cancer immunotherapy approvals it previously granted. A handful that the agency cleared under its “accelerated approval” pathway — meant to speed promising new drugs to market — have since come up short in confirmatory testing. A few drugmakers have withdrawn previously approved indications, while others like Regeneron and Incyte have pulled new applications.

Although Lilly and Innovent are seeking a standard approval for sintilimab, they are doing so amid an apparent shift in the FDA’s thinking.