Cancer drug by Innovent, Eli Lilly faces FDA hurdle due to China-only clinical tests, suggesting bumpy road abroad for Chinese pharmaceutical firms

FDA says Hong Kong-listed Innovent Biologics and partner Eli Lilly should conduct additional clinical trials on Sintilimab to demonstrate applicability for US patients
Tighter reviews and higher trial costs will make it more difficult for smaller Chinese biopharmaceutical companies to enter the US market and expand overseas, industry says

Medicine

Martin Choiin Hong Kong,Peggy Sitoin Hong KongandDaniel Renin Shanghai

Published: 5:57pm, 11 Feb 2022

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United States drug administrators have asked a Chinese pharmaceutical firm to broaden the clinical tests for its joint-venture cancer treatment, a move that could slow down Chinese biopharmaceutical companies’ entry into the US market.

The Oncologic Drugs Advisory Committee (ODAC) of the US Food and Drug Administration (FDA) said overnight on Thursday that Hong Kong-listed Innovent Biologics and its partner, US pharmaceutical giant Eli Lilly, should conduct additional clinical trials on their Sintilimab injection to demonstrate “applicability to US patients and US medical care” before the monoclonal antibody treatment can be approved for use.

“The application is reflective of an increasing number of oncology development programmes based solely, or predominantly, on clinical data from China,” the ODAC briefing document said, adding that the applicants did not consult the FDA “regarding trial design or conduct”. The committee voted 14-to-1 in favour of additional trials.

“US trials typically cost 3-5 times that of China, raising the bar for many,” said Bruce Liu, a China-based partner at strategy consultancy Simon-Kucher and Partners. The result of the meeting was “expected all along”, he added.

Industry players said tightened reviews and the three to five times higher trial costs in the US would make it more difficult for smaller Chinese biopharmaceutical companies to enter the US market and expand overseas.

Sintilimab, developed and commercialised by Innovent and Eli Lilly, is used for the treatment of non-small cell lung cancer and Hodgkin’s lymphoma alongside chemotherapy. It was approved for sale in mainland China after clinical trials in 2018. But that is not enough for it to qualify for use in the US, because the trial “enrolled a patient population which lacks the racial and ethnic diversity of the US population, notably with regards to currently underserved groups”, the ODAC document said.

Single-country submissions are a step backward in “achieving the racial diversity that we need in the United States”, Richard Pazdur, director of the FDA’s Oncology Center of Excellence, told the panel.

This “case will have far-reaching implications”, said Meng Tianying, a senior executive with Shanghai-based consultancy Domo Medical. “Other Chinese drug companies seeking to tap the US market are likely to be required to conduct clinical trials outside the mainland before they can receive FDA approval,” she said.

Helen Chen, a Greater China managing partner at LEK Consulting based in Shanghai, however, said the ODAC decision was good for the development of innovative biopharmaceutical companies coming out of China and Asia. Some Chinese drug makers have been preparing for multi-clinical centres for global expansion, she said.

An LEK analysis of companies with innovative oncology assets in China showed that 15 per cent of companies were already conducting international multicentre trials with a portion of their assets. They were already planning to have a broader patient set, Chen said.

“The immediate challenge is for companies with what I call ‘opportunistic’ filings – those who made the assumption that they can just take their China results to the US, perhaps without even a consultation with the FDA of the US,” she said.

04:23

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Chinese biopharmaceutical companies with overseas ambitions should familiarise themselves with the requirements of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and the FDA in terms of multi-region clinical trials, as well as trial design and endpoint considerations, said Liu of Simon-Kucher.

Liu added that there were different ways for doing trials outside China. Some Chinese players had teamed up with clinical research organisations, or joined forces with multinationals through partnership and licensing deals, or gone all-out to build clinical teams in those markets to ensure quality and speed, like BeiGene.

A 100mg dosage of Sintilimab Injection, produced by Innovent Bio and Eli Lilly. Photo: Innovent

Innovent remained confident about Sintilimab, said Michael Yu Dechao, the company’s co-founder and chairman. “The company will continue pursing our strategy of transforming into a global biopharmaceutical company and bringing high-quality innovative medicines to patients around the world,” he said in a filing to the Hong Kong exchange on Friday.

“While we are disappointed with the outcome of today’s ODAC, as it relates to the investigational product Sintilimab, we appreciated the opportunity to publicly discuss the application and broader issues related to single-country clinical trials,” Eli Lilly said in a statement on Thursday. “We had hoped that Sintilimab could have played a positive role for patients and the US health care system through an aggressive pricing strategy.”

Both companies said they would continue to work with the FDA as it completes its review of the Sintilimab application.