FDA's CDER Director Sparks Controversy Over Surrogate Endpoints in Drug Approvals

The pharmaceutical industry is abuzz following controversial comments made by Dr. George Tidmarsh, director of the FDA's Center for Drug Evaluation and Research (CDER), regarding the use of surrogate endpoints in drug approvals. In a now-deleted LinkedIn post, Tidmarsh singled out Aurinia Pharmaceuticals' lupus nephritis drug Lupkynis as an example of the potential shortcomings in relying on such endpoints.

Surrogate Endpoints Under Scrutiny

Tidmarsh's comments have ignited a debate on the FDA's approach to drug approvals, particularly in cases where surrogate endpoints are used to demonstrate efficacy. "We have approved drugs with significant toxicity like vocolosporin [Lupkynis' active ingredient] that has not been shown to provide a direct clinical benefit for patients," Tidmarsh wrote. He further claimed that "for some diseases such as lupus nephritis, companies have not run trials to demonstrate a benefit on hard clinical endpoints."

The CDER director's statements suggest a potential reevaluation of the FDA's use of surrogate endpoints in the drug approval process. This shift could have far-reaching implications for pharmaceutical companies developing treatments for complex diseases where traditional clinical endpoints may be challenging to measure in the short term.

Aurinia Pharmaceuticals in the Spotlight

Aurinia Pharmaceuticals, the company behind Lupkynis, found itself at the center of this controversy. The FDA approved Lupkynis in 2021 for the treatment of lupus nephritis based on pivotal data showing a significant decline in urine protein creatinine ratio, a surrogate endpoint measuring protein levels in the kidney. The approval was also supported by data indicating that patients treated with Lupkynis plus standard of care were more than twice as likely to see renal response.

Following Tidmarsh's comments, Aurinia's stock took a significant hit, closing down 15.8% on Monday. The company has continued to evaluate Lupkynis, with the AURORA 2 extension study leading to an FDA label update in April 2024, confirming higher sustained complete renal response rates versus placebo over three years.

Industry Implications and Personal Connections

Tidmarsh's critique of surrogate endpoints and his specific mention of Lupkynis have raised eyebrows in the industry, particularly given his past connections to key figures at Aurinia. Kevin Tang, chairman of Aurinia's board of directors, is well-known in the biotech world for his company Concentra Biosciences, which acquires struggling biotechs. Tang Capital Management is currently Aurinia's largest shareholder.

Notably, Tidmarsh and Tang have a shared history at La Jolla Pharmaceuticals, where Tang served as chairman and major shareholder, and Tidmarsh as CEO until his departure in November 2019. This connection has led some industry observers to question the motivations behind Tidmarsh's public statements.

As the pharmaceutical industry grapples with the implications of these comments, many are watching closely to see how the FDA will address the use of surrogate endpoints in future drug approvals and what this could mean for ongoing drug development programs.