A diabetes breakthrough in search of patients

by Lisa Jarvis

In a first, the U.S. Food and Drug Administration has approved a therapy that slows the onset of Type 1 diabetes. Teplizumab, developed by Provention Bio, typically delays the need for insulin shots, blood-sugar monitoring, and diet control by about two years. For some, the effect lasted years longer.

The treatment could be a way to delay the life-changing regime of managing diabetes, which is often diagnosed in children or adolescence. Unfortunately, there are many hurdles to overcome before the drug can make a real difference. The most immediate and daunting problem: getting the treatment to the right people at the right time.

A drug that can slow the onset of the disease is a gift to people destined to develop Type 1 diabetes, which affects roughly 1 million to 1.5 million Americans. “You don’t do anything if you have diabetes without thinking about the diabetes,” says Kevan Herold, a professor at Yale School of Medicine who was involved with the clinical studies of teplizumab. “You don’t eat, you don’t exercise, you don’t sleep, you don’t go to school [without thinking about it] — it’s there all the time.”

Type 1 diabetes occurs when the immune system wages war on beta cells, the clusters of insulin-making factories in the pancreas. Eventually, so many of those factories have been depleted that people become reliant on insulin injections to regulate their blood sugar. (By contrast, people with Type 2 diabetes can often still make insulin but can’t process it.)

Provention’s drug intervenes in that early battle. The antibody, administered as a daily infusion over the course of two weeks, dampens the activity of the immune cells that are causing the damage.

Maximizing that effect will be a huge challenge. For one, insurers will need to get on board. They may balk at a one-time regimen that costs nearly $200,000 yet still isn’t a cure.

The other issue is finding patients. To participate in the study that led to the drug’s approval, volunteers had to meet a number of criteria: a family member with Type 1 diabetes, at least two markers of the disease, called autoantibodies, and signs of blood sugar dysregulation.

Those criteria describe a small subset of a much larger population of people with Type 1 diabetes. The vast majority, some 85%-90%, don’t have a familial link to the disease. Nor is it a routine part of pediatric care to screen for it. And for good reason: the tests can be expensive and unpleasant (as anyone who has been pregnant may remember).

There are two ways to figure out who might benefit from the drug, according to JDRF, a diabetes-focused advocacy group that helped fund the development of tepliziumab through its venture philanthropy arm. The first would be to look for genetic markers linked to the disease in the heel-prick test every baby gets at the hospital. Not everyone who has those markers will go on to develop diabetes, but the screen could flag children who should be more closely monitored during their early life, says JDRF chief executive officer Aaron J. Kowalski.

The second approach is to look for the autoantibodies detectable in blood before symptoms show up. Researchers have found that a person with two or more of these markers along with abnormal blood sugar has a 75% chance of needing to rely on insulin within the next five years — and a nearly 100% chance of it in their lifetime.

But those tests need to become much more user-friendly and affordable, an effort JDRF is funding. It’s a scientific challenge more diagnostics companies should tackle.

If the right patients can be more readily identified — and that’s still a big if — the other question is whether the benefits of the drug can be strengthened. Teplizumab is currently approved as a one-time regimen. But doctors want to know if Type 1 diabetes could be further delayed if, for example, the treatment was administered repeatedly — and if so, how often? And could it help people newly diagnosed, who might still have some functioning beta cells to preserve?

Instead of a two-year delay, “wouldn’t it be nice if it was 8-10 years? Or 10-20 years? Or obliterated altogether?” says Bruce Perkins, director of the Sinai Centre for Diabetes, at Toronto’s Mount Sinai Hospital. “This is just the starting point, but it gives us so much hope.”

That hope took decades to materialize. The treatment traded hands among biotech and pharma companies as it trudged through clinical studies. It took several champions, and investment from JDRF’s venture philanthropy group, to finally heave the drug over the finish line.

It’s rare to land on treatments that can so clearly delay the course of a disease — not to mention ones that whisper of putting off the disease for long enough they start to look like prevention. Getting this therapy to the people who need it shouldn’t also be a years-long slog.

Lisa Jarvis is a Bloomberg Opinion columnist covering biotech, health care and the pharmaceutical industry. Previously, she was executive editor of Chemical & Engineering News.