FDA Official's LinkedIn Post Sparks Controversy Over Surrogate Endpoints and Lupus Drug

In a surprising turn of events, the pharmaceutical industry has been thrust into a debate over the use of surrogate endpoints in drug approvals, following a now-deleted LinkedIn post by Dr. George Tidmarsh, director of the FDA's Center for Drug Evaluation and Research (CDER). The post, which singled out Aurinia Pharmaceuticals' lupus nephritis drug Lupkynis, has raised questions about the FDA's stance on surrogate endpoints and the potential implications for drug development and approval processes.

Tidmarsh's Post and Its Implications

Dr. Tidmarsh's LinkedIn post claimed that the CDER would be reevaluating the use of surrogate endpoints for drug approvals. He specifically mentioned Lupkynis (voclosporin), stating that it has "significant toxicity" and "has not been shown to provide a direct clinical benefit for patients." Tidmarsh also asserted that for diseases like lupus nephritis, companies have not conducted trials to demonstrate benefits on "hard clinical endpoints" such as progression to end-stage renal disease.

The post has since been deleted, and Tidmarsh clarified that his statements were personal views and did not reflect those of the FDA or the Department of Health and Human Services. However, the incident has sparked industry-wide discussions on the validity and future of surrogate endpoints in drug development.

Aurinia Pharmaceuticals' Response and Drug Profile

Aurinia Pharmaceuticals, the company behind Lupkynis, saw its stock price drop by 15.8% following Tidmarsh's comments. The company quickly responded, reaffirming its confidence in Lupkynis' risk-benefit profile. Aurinia highlighted that Lupkynis received full FDA approval in 2021 based on data showing higher renal response rates and quicker decline in urine protein creatinine ratio (UPCR) compared to standard-of-care treatment alone.

The company also pointed out that the FDA approved an application for long-term use of Lupkynis in 2024, based on results from the AURORA 2 extension study. This study demonstrated the drug's continued efficacy over three years, with a safety profile consistent with previous trials.

Wider Industry Implications and Reactions

The controversy surrounding Tidmarsh's post has raised concerns about the potential impact on other drugs approved using surrogate endpoints. Analysts at Evercore ISI suggested that companies like Sarepta Therapeutics, which has several exon-skipping therapies for Duchenne muscular dystrophy (DMD) approved based on surrogate endpoints, could face increased scrutiny.

The incident has also highlighted the unusual nature of a high-ranking FDA official using personal social media to comment on specific drugs and approval processes. This has led to discussions about the appropriate channels for regulatory communications and the potential conflicts of interest within the industry.

As the pharmaceutical sector grapples with these developments, many are watching closely to see how the FDA will address the use of surrogate endpoints in future drug approvals and whether this incident will lead to broader policy changes in the industry.