US slams the door on low cost immune therapies from China

Low cost immune therapies for oncology may be the next victim of the US-China geopolitical rivalry with the FDA backtracking on its previous welcoming stance towards China’s large pipeline of immune checkpoint inhibitors.

The agency last week rejected one of the first immunotherapy applications from a Chinese company, Innovent, for its PD-1 inhibitor sintilimab for the frontline treatment of metastatic non-small cell lung cancer. The drug is priced at only $6000 a year in China whereas PD-1 inhibitors currently approved in the US cost $100,000 or more a year.

The drug, which is one of an estimated 25 new oncology therapies in development in China, was co-sponsored by Eli Lilly and supported by evidence from the ORIENT-11 phase 3 trial that compared it against pemetrexed/platinum in NSCLC.

However in a strongly-worded briefing document the FDA Oncology Panel cited numerous reasons for rejection, saying it was concerned about “an increasing number of oncology development programs based solely or predominantly on clinical data from China.”

The FDA said it wanted to see data from multiregional trials for oncology therapies rather than single country trials that did not “reflect the diversity of the American population”.

It added that the company had not consulted with the FDA regarding trial design and conduct, and it now wanted to see overall survival as the outcome for new oncology therapies rather than progression free survival.

“Acceptance of PFS for a me-too trial design and drug, in a trial population that does not reflect a U.S. demographic, represents a departure from the FDA regulatory precedent in this space,” it said.

Change of tune

The harsh wording of the FDA rejection of sintilimab was in stark contrast to positive comments made earlier by Dr Richard Pazdur of the FDA’s Oncology Center of Excellence.

In 2019 he told the American Association for Cancer Research (AACR) meeting that he would like to see China ‘s biotech companies bringing their low cost PD-1/PD-L1 inhibitors to disrupt the $100 billion US market for oncology immunotherapies dominated by high cost products.

They “could potentially be a great thing for everyone because we haven’t seen the major western pharmaceutical companies moving on price,” he said, according to an article in BioCentury.

But Dr Pazdur appears to have changed his tune in recent article in Lancet Oncology published in February 2022. Entitled “Importing oncology trials from China: a bridge over troubled waters?” he echoed many of the criticisms of ‘foreign trials’ expressed in the FDA briefing document and called for multi-regional clinical trials (MRCTs) rather than single country trials supplemented by bridging studies.

“Many current applications that rely on clinical data from China are similar to previously conducted MRCTs that led to US approval and, hence, do not fulfil an unmet need,” he wrote.

“Most of these drugs are checkpoint inhibitor antibodies; China’s Centre for Drug Evaluation cites more than 100 investigational new drug applications for this class. The degree of regulatory flexibility in establishing the acceptability of data from a single country and its generalisability to a new population should be balanced against the drug’s innovation,” said Dr Pazdur.

The advent of low cost immunotherapies has forced US pharma companies to slash the prices of their products to gain listings in China. At the same time, the US government has identified China’s biotech sector as a key strategic competitor to American industry and is implementing restrictions on trade and scientific collaboration.

On 8 February one of China’s biggest biotech companies, Wuxi Biologics, was among 33 Chinese high-tech organisations added to a black list by the US Commerce Department.

The company, a major producer of monoclonal antibody products, was added to the US governments ‘unverified’ list that restricts access to US exports on security grounds.

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