There’s been more good news for Teplizumab, the promising drug that may delay the onset of Type 1 diabetes and even potentially prevent it from developing.
In 2019 we reported on the biggest trial that Teplizumab had completed to date:
Teplizumab was given in a single 14-day course to a group of 44 participants that had been identified as at high risk for development of T1D. A placebo group of 32 high risk participants was also monitored. Patients were followed for seven years, during which 72% of the control group was diagnosed with T1D, compared to only 43% of the teplizumab recipients. Moreover, among those that did develop full blown T1D, the drug appeared to delay onset by an entire two years. The trial was a resounding success.
Now, the same group of participants have been studied for an additional year. The results, according to Dr. Francisco Leon, were “ideal.” That extra year showed an extra year of benefit, as the course of medicine continued to delay and/or prevent T1D eight years later.
Dr. Leon is the Chief Scientific Officer and co-founder of Provention Bio, the company that has developed Teplizumab, which has “declared as our sole focus the prevention of immune diseases.” He spoke to ASweetLife about his hopes for his business’ star product.
Teplizumab was originally developed over twenty years ago as an immunosuppressant to prevent rejection of transplanted organs or cells. Its potential to treat Type 1 diabetes soon became clear when researchers realized that it was particularly effective at quieting the CD8+ T cells that cause Type 1 diabetes by destroying one’s own beta cells.
“It switches the function of these T cells from being ultra-reactive—destructive of beta cells—to being so-called ‘exhausted’ cells. They no longer destroy the beta calls.”
When given to patients at an especially high risk of developing T1D, a 14-day course of treatment with Teplizumab causes a change in these T cells that can last for eight years or more. And the immune system doesn’t seem to be weakened in any other way.
Patients were identified as high risk through autoantibody screening—participants were only enrolled if they tested positive for two or more of the autoantibodies known to precipitate beta cell destruction. In fact, the term “high risk” is now considered bit of misleading nomenclature. Dr. Leon told me that “what’s called at risk is in reality early stage T1D.”
“Type 1 diabetes is a continuum. Once you have two or more autoantibodies, you have the disease. Because everybody that has two or more will eventually become insulin dependent. One-hundred percent.”
This classification was set forth in a joint scientific statement by the leading American diabetes organizations. In stage 1 of T1D, a patient has two or more autoantibodies but is otherwise presymptomatic. In stage 2, beta cell destruction has led to dysregulated glucose levels, but the patient has yet to develop noticeable symptoms. Stage 3 represents fully-fledged diabetes, announced by the symptoms of critical insulin deficiency already familiar to anyone that’s been diagnosed with the disorder: extreme thirst, weight loss, and so on.
Only a very tiny minority of new patients are diagnosed with T1D while they’re in stage 1 or stage 2. And as many as half are diagnosed only after experiencing diabetic ketoacidosis, an extreme and dangerous consequence of untreated stage 3. Autoantibody testing of family members isn’t considered obligatory, and even when it does confirm early-stage T1D, doctors cannot prescribe any therapies to stem the progress of the disease. They can only recommend increased vigilance.
Teplizumab may change all of this. If one family member has Type 1 diabetes, “the risk is 15 times greater in first degree relatives. So, if one family member gets diagnosed, everybody should get tested.” And if another family member is found to have early stage T1D, Teplizumab could make a huge difference in the disease progression.
For those interested in autoantibody screening, Dr. Leon strongly recommended T1Detect, a new screening program organized by JDRF and sponsored by Provention Bio. It’s a simple at-home kit that costs $55, with options for lower prices for those that cannot easily afford it.
Patients who learn they have only one autoantibody have about a 50% chance of going “back to normal,” and never developing Type 1 diabetes at all. For such patients, “the risk-benefit analysis is less obvious, because you might go back to zero antibodies by yourself. Even we don’t believe you should be getting an immune modulator.” Provention Bio has no plans to study the use of Tepluzimab in patients with only one autoantibody.
In May, a committee of experts will vote on whether or not to recommend the drug for FDA approval. If all goes well, Provention will receive that FDA approval in June or early July, and could begin providing the treatment to patients before autumn.
Insurance companies have already told Provention that they are eager to cover both antibody screening and Teplizumab itself. This is easy to believe. While we’ve seen that some diabetes therapies, like continuous glucose monitoring, have not been immediately embraced by payers, in this case the financial benefit of the drug seems obvious—a two- or three-year delay in the progression of T1D means two or three years without having to pay for insulin, syringes, test stripes, pumps, etc. It’s a win for both patient and insurer alike.
Approval for a single course of Tepluzimab in patients with stage 1 or stage 2 T1D could just be the beginning: “We are going to study further dosing. Can you dose again after two years, or three years? Can you get another two or three years of benefit? Could you pass puberty by dosing three or four times over the course of ten years? Once you pass puberty, the risk of conversion is much lower… this is yet to be tested. It’s a hypothesis. But once we have Teplizumab on the market we’ll these pursue these studies to see if we can prolong the delay, potentially indefinitely.”
Additionally, Dr. Leon hopes that Teplizumab, which “rescues previously dysfunctional beta cells,” can also prove useful to patients that have already been diagnosed with Type 1 diabetes. Another exciting possibility is the use of Teplizumab with beta cell transplantation.
Even if further study shows that Teplizumab cannot prevent T1D onset and can only delay it, the potential benefits are enormous. The opportunity to enjoy several extra years of healthy metabolism, and to carefully monitor disease progression, could save a remarkable amount of both stress and money. And, as Dr. Leon says, “The sooner you catch the disease, the greater the benefit.” Those extra years of health will also result in meaningfully lower risks of diabetic complications years down the line.
“This is the paradigm shift. Why wait until all the beta cells have already been destroyed? We can screen for autoantibodies with a simple blood test and intercept the disease early. We believe this paradigm can change the course of Type 1 diabetes.”