A now-deleted LinkedIn post from a top FDA official has raised the hackles of Aurinia Pharmaceuticals as industry watchers puzzle over the official's decision to target the approvability of surrogate endpoints—and single out Aurinia’s lupus nephritis med Lupkynis—via social media.
Monday, George Tidmarsh, M.D., Ph.D., leader of the FDA’s Center for Drug Evaluation and Research (CDER), claimed on his personal LinkedIn page that Lupkynis, also known as voclosporin, carries “significant toxicity” and “has not been shown to provide a direct clinical benefit for patients.”
Aurinia won its first-ever FDA nod when the regulator cleared the biotech's calcineurin inhibitor Lupkynis in combination with a background immunosuppressant for lupus nephritis patients in early 2021. The drug boasts a full, standard FDA approval, which is curious considering Tidmarsh seemed to be railing against the use of surrogate endpoints to inform accelerated green lights.
The Lupkynis callout came alongside a pledge from Tidmarsh that the “CDER will be evaluating surrogate endpoints used for FDA approval.” While caveating that those surrogate endpoints have benefited patients by bringing treatments to market sooner, he argued that there have been “notable failures in confirmatory trials, such as those for exon skipping therapies in [Duchenne muscular dystrophy (DMD)].”
In the case of lupus nephritis drugs, Tidmarsh suggested that “companies have not run trials to demonstrate a benefit on hard clinical endpoints like progression to end stage renal disease.”
“We will be taking a close look at the use of surrogate endpoints to see where we can further accelerate promising drugs faster while requiring companies to perform the trials necessary to confirm actual clinical benefit,” the post concluded.
Tidmarsh subsequently clarified that the post reflected his own views and did not represent the opinions of the FDA or the Department of Health and Human Services, Stat reported Monday. Both posts have since been deleted.
The use of a personal social media account by an FDA official as a bully pulpit to go after a specific drug is highly unusual, if not unheard of, Stat pointed out.
Aurinia’s 2021 approval hinged on data showing Lupkynis led to higher renal response rates and a quicker decline in urine protein creatinine ratio (UPCR) versus standard-of-care lupus nephritis treatment alone. UPCR is a measure used to monitor protein levels in the kidney, with Aurinia noting at the time of its approval that early intervention and kidney response are linked to better long-term outcomes and the prevention of irreversible kidney damage in lupus patients.
Aurinia’s stock plummeted Monday from a value of $13.31 to $10.88 at the low end following Tidmarsh’s post. The stock was trading flat Tuesday morning at a value of $11.06.
The company quickly sought to parry the LinkedIn claims, noting in a press release that it continues to stand behind Lupkynis’ risk and benefit profile.
Aside from touting the large Aurora 1 trial that earned the drug its approval in 2021, Aurinia clarified that the FDA last year approved its application for long-term use of Lupkynis using results from a separate study that showed the medicine remained effective over three years. In that long-term study, dubbed Aurora 2, Lupkynis’ safety profile was on par with results observed in the previous trial, Aurinia said.
It’s unclear what inspired Tidmarsh’s Lupkynis invective, although Stat speculated it might have something to do with Tidmarsh’s connection to Aurina’s board chair Kevin Tang, whom Tidmarsh worked with previously at La Jolla Pharmaceuticals. Tidmarsh left La Jolla in 2019 in what a Securities and Exchange Commission filing at the time described as a resignation. In a press release issued in tandem with Tidmarsh’s departure, Tang noted that the current CDER chief had exited the company to “pursue other interests,” according to Stat.
Tidmarsh was tapped to head up the CDER this summer following a lengthy career in the biotech world, having helped found a slew of companies like Metronome Therapeutics, Revelation Biosciences and the Amgen-acquired Horizon Therapeutics.
Tidmarsh’s priorities in the new role were not immediately clear, although he had previously voiced a desire for the FDA to “remove harmful, useless drugs from the market”—also on LinkedIn—and has challenged instances of misconduct and fraud in academic science.
Meanwhile, if the CDER is indeed ramping up scrutiny on surrogate endpoints—and taking a close look at exon skippers in DMD specifically as Tidmarsh suggested—companies like Sarepta Therapeutics could be caught in the crossfire, analysts at Evercore ISI wrote in a Monday note to clients.
The odds of Sarepta’s exon-skipping DMD therapies—which include Exondys 51, Vyondys 53 and Amondys 45—being pulled from the market “just went up” in the aftermath of Tidmarsh’s post, the analysts argued. If those therapies were withdrawn in the U.S., Sarepta would suffer a “huge negative impact,” the Evercore team said.