FDA grants Breakthrough Therapy Designation to teplizumab for prevention/delay of type 1– August 6, 2019

First FDA breakthrough designation for type 1 delay/prevention; No formal timeline given but update in “coming months”; Landmark results at ADA 2019

Provention Bio just announced that FDA has granted Breakthrough Therapy Designation (BTD) to teplizumab (PRV-031) for the prevention or delay of clinical type 1 diabetes in at-risk individuals.

BTD is intended to expedite the development and review process of drugs that (i) treat a serious condition; and (ii) demonstrate significant improvement in a clinically-relevant endpoint compared to the therapies that are currently available. With BTD, Provention will be privy to (i) more intensive and interactive guidance from FDA regarding an efficient drug development program; (ii) access to a scientific liaison to help expedite review time; and (iii) potential eligibility for Priority Review. This is a major win for Provention (along with the entire type 1 community) and should help streamline the regulatory process for teplizumab. It also reinforces how on a roll the T1D Fund is – they invested in Provention last year.

The designation comes on the heels of landmark phase 2 data presented at ADA 2019 which showed that a single 14-day course of intravenous teplizumab produced marked reductions in clinical diabetes onset (43% vs. 72% on placebo; HR = 0.41; p=0.0006) and significant increases in time to diagnosis (48 months vs. 24 months). With these impressive results, teplizumab became the first drug ever to meet a clinical endpoint in delaying type 1 onset.

According to Provention Bio, the company intends to discuss next steps with FDA and provide an update in “the coming months.” We are thrilled that FDA appears to also see the immense impact this treatment could have moving forward.

  • As a reminder, Provention Bio acquired development rights to PRV-031 from MacroGenics in May 2018. The company is also assessing the candidate in a phase 3 pivotal trial (PROTECT, n=~300) assessing teplizumab’s ability to slow the loss of beta cells and preserve beta cell function in children and adolescent 8-17 years old who have been diagnosed with type 1 in the previous 6 weeks. This trial began in April 2019 and is expected to complete in May 2022.
  • Currently, TrialNet is investigating two other immune therapies to delay or prevent type 1 diabetes through its Pathway to Prevention screening program. First, the organization is testing whether hydroxychloroquine can prevent Stage 1 diabetes, where two or more type 1 autoantibodies are present, from progressing to Stage 2, and ultimately clinical diabetes, in a currently-enrolling study. Second, abatacept is being investigated in the same manner; previous research on newly-diagnosed (Stage 3) individuals showed that abatacept improved insulin production and delayed insulin loss.
  • Otelixizumab, another anti-CD3 monoclonal antibody, is also being studied by GSK; however its pipeline status remains unclear. No updates on the compound were given in the company’s 2Q19 financial earnings call, although a new December 2018 publication in the British Journal of Clinical Pharmacology showed that maximum target engagement was found at 18 and 27 mg cumulative doses and stated that the findings will be “useful in guiding dose selection in clinical trials.” The candidate was originally studied in a phase 2 trial in new-onset type 1 diabetes, which was apparently completed in September 2018, but no results have been given by the company since. Some hope that teplizumab’s recent momentum will spur GSK to reinvest in otelixizumab and potentially pivot the candidate toward earlier prevention rather than clinical diabetes treatment but we doubt this will happen given the impression we had from JP Morgan in offhand conversation with the CEO. Many would not view further investment by GSK as a good investment of GSK resources. We would disagree with this but it’s hard to change the minds of those that mainly want to invest further in cancer and we certainly understand how large the needs are there and how it is an easier therapeutic area for some organizations to work in currently. For more, see our full type 1 cure/prevention/treatment landscape here.


--by Rhea Teng, Martin Kurian, and Kelly Close