- The Food and Drug Administration has decided not to approve what could have been a first-of-its-kind medicine meant to delay the onset of Type 1 diabetes, an autoimmune disease which affects more than 1 million people in the United States.
- Provention Bio, the New Jersey-based company developing the medicine, said it received a rejection letter on July 2. In the letter, the FDA took issue with a so-called bridging study that looked at how Provention's medicine gets absorbed and takes effect in the body when made with drug product from two different sources.
- Provention said it expects to collect data that could address the FDA's concerns before the end of September, from a sub-study of the large, late-stage clinical trial currently testing its medicine, known as teplizumab. In the meantime, the company's shares are trading at just over $6 apiece, down 30% from last week and 65% since the start of this year.
While managed with insulin shots, Type 1 diabetes can still shorten expected life spans by more than a decade. A drug that prevents the disease, even for a time, could therefore be revolutionary for the millions of people living with it.
Provention hopes it has such a drug in teplizumab, an engineered antibody that's supposed to regulate the immune system by targeting a cluster of proteins known as CD3.
In 2019, a small study of people believed to be at risk for Type 1 diabetes found that those who were given Provention's drug went longer before developing the disease. The median time to diagnosis was just over four years for teplizumab-treated participants, versus two years in the placebo group.
The annualized rates of diagnosis were also lower in the teplizumab arm compared to the placebo arm, at 15% and 36%, respectively.
That data, which were published in The New England Journal of Medicine, provided the support Provention needed to submit its drug for approval. The company completed an application late last year, and by January the FDA had agreed to give it a speedy review, with a decision expected no later than July 2.
Since then, the drug's odds of approval have appeared to swing up and down. In early April, for example, Provention disclosed that the FDA found "deficiencies" in its application — issues the company thought must be tied to its bridging study.
Historically, the drug product for teplizumab was manufactured by Eli Lilly, and it was this product that Provention used in its pivotal study. Provention, though, wants a Seattle-based contract manufacturer called AGC Biologics to make the product should teplizumab come to market. So the company conducted a bridging study to show the AGC product works just as well.
According to the Provention, the week before FDA officials flagged those application "deficiencies," they had expressed concerns about the two drug products tested in the bridging study, ultimately concluding they didn't seem comparable based on the available evidence.
Yet, by late May, approval seemed a bit more likely. The FDA had just convened an outside group of experts to assess whether the benefits of teplizumab outweigh its risks, and the group determined they did, voting 10-7 in favor of the drug. (As an immune system suppressant, teplizumab did lead to lower levels of a certain kind of white blood cell in a majority of participants treated with it.)
But while the FDA typically follows its advisors' recommendations, that's not always the case, as exemplified by Friday's rejection.
Indeed, the bridging study looks to be a focal point of the FDA's decision. According to Provention, the agency said the study failed to show the two drug products are comparable, and that the company must either establish comparability or provide data that justify why it's not necessary.
Provention expects to have more supportive data later in the third quarter.
The company said a couple other issues were raised in the rejection letter, but believes most of them can be dealt with soon, or have already been addressed through recent amendments to the approval application. The FDA apparently also found deficiencies during a recent general inspection at a fill-and-finish manufacturing facility used by Provention that will need to be resolved before teplizumab can be approved.
Provention said the deficiencies were not specific to teplizumab, and that the FDA has not flagged any problems related to the drug's efficacy and safety data packages.