'We kept at it': Jeffrey Bluestone plots late-stage comeback after teplizumab shown to delay type 1 diabetes
Late-stage data presented at the American Diabetes Association annual meeting in 2010 pushed Eli Lilly to put a crimp on teplizumab as the pharma giant found it unable to reset the clock on newly diagnosed type 1 diabetes. At the same conference but in different hands nine years later, the drug is making a critical comeback by scoring success in another niche: delaying the onset of the disease.
In a Phase II trial with 76 high-risk individuals — relatives of patients with type 1 diabetes who have diabetes-related autoantibodies in their bodies — teplizumab almost doubled the median time of diagnosis compared to placebo (48.4 months versus 24.4 months). The hazard ratio for diagnosis was 0.41 (p=0.006).
Investigators added that teplizumab’s effects seem strongest in the first year, when progression to type 1 diabetes was also the greatest in the overall trial population. In that year, only 3 of 44 teplizumab participants was diagnosed, compared to 14 of 32 in the placebo arm. All told, the diagnosis rates at the end of the trial were 43% (19/44) and 72% (23/32), respectively.
With less than three years of median follow-on after a 14-day regimen, the results don’t say much about the potential for prevention or even cure but do support the idea that immune modulation could buy time for patients who appear doomed for a life dependent on insulin.
Teplizumab, which targets CD3, is designed to diminish CD8+ T lymphocytes’ attacks on beta cells in the pancreas, eventually depleting these insulin generators.
“(T)hese data provide strong albeit indirect evidence about the pathogenesis of beta-cell destruction and the potential to modify the course of type 1 diabetes with newer biologic agents,” Clifford Rosen and Julie Ingelfinger of the Maine Medical Center Research Institute wrote in an accompanying editorial in the New England Journal of Medicine.
It’s also a victory for Jeffrey Bluestone of UCSF and Kevan Herold of Yale, who have maintained their confidence in teplizumab since they began working on its application in diabetes in the ealry 1990s. Bluestone convinced Provention Bio to pick up the drug before jumping on its board to help steer the clinical study. Provention Bio $PRVB surged more than 400% to $22 at one point, ending the day up 217%.
“(N)ow the real hard work begins,” Bluestone told Science with regards to the next steps.
Recruiting patients, especially children, might prove a challenge in new placebo-controlled studies. Notably, the size of this current trial was cut by almost half due to slower-than-expected rates of enrollment. Moving forward, large-scale screening efforts will also be required to extend the drug’s reach to at-risk individuals with no family history of diabetes.
“The key next step of course is seeing whether this drug can cross the finish line through upcoming Phase III trials and get approved by the FDA. There’s still lots to do – but hopefully this speeds things up a bit,” Bluestone added in a statement.
Image: Jeffrey Bluestone — UCSF via Parker