Experimental Drug Called Teplizumab Actually Delayed Type 1 Diabetes in Yale Investigator-Led Trial

Teplizumab Actually Delayed Type 1 Diabetes

Investigational drug Successfully delayed progression of type 1 diabetes in young, at risk patients—a breakthrough milestone—representing a new chapter in diabetes drug research?

Over 1 million in the U.S. are affected by type 1 diabetes. The autoimmune disease necessitates continuous attention to blood sugar levels as a matter of life and death. The omnipresent specter of long-term complications such as heart disease, blindness and kidney failure loom for the patient.

Researchers now know type 1 diabetes starts before its ever diagnosed.   The disease initiates is attack quietly, led by T cells, detectable event via antibody markers in the blood.  As the battle commences, the pancreas’ beta cells remain mostly intact, representing a window of opportunity to not only learn more about the entire disease, but also to intervene and save them, reports Jennifer Couzin-Frankel writing for Science.

The Study

Kevan Herold, a researcher at Yale, had been on the research trail to reverse diabetes for years.  Ms. Couzin-Frankel drills into some of this fascinating history in sufficient detail for a decent coverage of the relevant events.

In 2011, Herold successfully pitched an anti-CD3 study to TrialNet, a network of physicians, scientists and healthcare teams at the forefront of type 1 diabetes research involving teplizumab.

The clinical trial started eight years ago and included 76 participants (out of a planned number of 144), young, at risk individuals for type 1 diabetes. Their ages ranged from 8 to their 40s.  About 70% were 18 years old and under. The investigators identified a mix of participants through network of screening centers from North American through Europe and Australia established by TrialNet.

44 participants received teplizumab and 32 were given a placebo.  Both groups received 14 consecutive days of IV infusion. The study challenged to progress due to slow enrollment, arduous screening and likely skepticism as previous type 1 diabetes trials fared badly as did a teplizumab study sponsored by a large pharmaceutical company.

The Results: Did the Drug Delay the Onset of Type 1 Diabetes?

The difference between the placebo group and the teplizumab group “was stark” as Ms. Couzin-Frankel conveyed.   Those in the teplizumab treatment group had a median diabetes diagnosis time of 4 years while the placebo group was 2 years. Of those that received the experimental drug, 43% were diagnosed with diabetes after years, versus 72% receiving the placebo.  Of interest, participants with a certain gene variants who received teplizumab had a greater propensity to avoid the disease.

Science reports that even a 2-delay in the disease is material—2 less years of insulin for a child has several implications not to mention the possibly lower risk for long-term complications: “Two weeks of teplizumab is a small price to pay for extra diabetes-free time” the author quoted one investigator.

Overall the safety features of teplizumab have been manageable.

What’s Next?

It is not clear what the next steps are for prevention studies.  Many challenges must be overcome including screening complications. The Herold study focused on first degree relatives with diabetes.  Most with diabetes don’t have a readily available family history so large scale screening would not be easy.  Will the public even participate?

Corporate ownership has switched hands—presently Provention Bio owns the underlying intellectual property—acquiring it from MacroGeneics.  Provention does have a handful of trials involving teplizumab for those already diagnosed with the condition.

Lead Research/Investigator

Kevan Herold, endocrinologist, Yale University