Provention Wins FDA Approval for First Drug to Delay Type 1 Diabetes Progression

Red seal and imprint "FDA APPROVED" on white surface. FDA - Food and Drug Administration is a federal agency of the United States Department of Health and Human Services.Red seal and imprint "FDA APPROVED" on white surface. FDA - Food and Drug Administration is a federal agency of the United States Department of Health and Human Services.

Type 1 diabetes patients whose disease has reached its most advanced stage require a lifetime of insulin therapy to keep at bay potentially life-threatening complications. A Provention Bio drug has received FDA approval as the first treatment that delays the onset this stage of the disease.

Approval of the Provention drug, teplizumab, covers adults as well as children age 8 and older whose type 1 diabetes (T1D) is classified as stage 2. Red Bank, New Jersey-based Provention will market its new product under the brand name “Tzield.”

Type 1 diabetes is an autoimmune disease in which the immune system attacks the insulin-producing beta cells of the pancreas. The decline in beta cell function is classified according to three stages. By the third stage, when most patients are diagnosed, a significant portion of beta cells have already been lost. These patients typically require regular insulin injections for life in order to manage blood glucose levels.

Tzield is an antibody designed to bind to CD3, a receptor on T cells that activates them and directs the immune response. Binding to this receptor is intended to deactivate T cells, preventing them from attacking beta cells. This approach is also intended to increase the proportion of regulatory T cells, a different type of immune cell that tamps down the immune response. While Tzield doesn’t stop type 1 diabetes, the drug is meant to delay the disease’s progression.

The FDA decision announced late Thursday is based on the results of a placebo-controlled study that evaluated 76 patients whose type 1 diabetes was classified as stage 2. Trial participants were randomly assigned to receive Tzield or a placebo, administered as an intravenous infusion once a day for 14 days. The main goal of the study was to measure the time it took for a patient to develop stage 3 disease.

Over a median follow-up period of 51 months, 45% of the 44 patients who received the Provention drug were later diagnosed with stage 3 diabetes compared to 72% of the 32 participants who received a placebo. The median onset of stage 3 diabetes was 25 months for the Tzield group compared to 50 months for the placebo group. The results were enough to show a statistically significant delay in the development of stage 3 type 1 diabetes. Data from the study were published last year in the New England Journal of Medicine.

“The resulting median delay of more than two years in the onset of stage 3 disease is a priceless therapeutic outcome for patients with stage 2 T1D,” Provention CEO Ashleigh Palmer said, speaking during a conference call on Friday.

Of course, Tzield does have a price. Provention set a wholesale cost of $13,850 per vial. That means the 14-day dosing schedule will cost $193,900. Dosing is according to patient weight and some patients may require additional vials. Provention will commercialize Tzield under a partnership agreement reached with Sanofi last month. According to the agreement, Provention keeps rights to Tzield but will contract Sanofi diabetes field specialists and other staff. Provention will reimburse Sanofi up to $33 million in fiscal 2023.

Sanofi committed $55 million to the alliance, which breaks down to a nonrefundable $20 million payment for the right of first negotiation for global rights to Tzield in type 1 diabetes. This negotiation right expires in June 2023, though it may be extended under conditions that were not specified. In addition, Sanofi agreed to purchase $35 million worth of Provention stock at a 40% premium by Feb. 16.

The most common side effect reported in clinical testing was a reduction in the levels certain types of white blood cells, rash, and headache. The drug’s label does flag the potential risk of cytokine release syndrome, an excessive immune response that was reported in 5% of patients who were given Tzield. This side effect can be mitigated by pre-medicating the patient and monitoring for signs and symptoms.

Last year, an FDA advisory committee voted 10-7 on the question of whether the Provention drug’s benefits outweigh its risks. Palmer said that as a condition of the Tzield’s approval, Provention has committed to setting up a registry to monitor long-term safety. The company will also conduct a pediatric study in type 1 diabetes patients younger than 8 whose disease has reached stage 2.

Additional studies are underway that could potentially support the expansion of the drug’s use to more type 1 diabetes patients. A Phase 3 study in newly diagnosed patients is fully enrolled; preliminary data are expected in the second half of next year, according to an investor presentation. Additional potential expansion opportunities include treating children between the ages of 2 and 8, repeat dosing of the therapy, and a subcutaneously injectable version of the drug. Provention is also exploring the drug in autoimmune conditions that include early rheumatoid arthritis, celiac disease, Crohn’s disease, and autoimmune hepatitis.

Provention licensed Tzield from Macrogenics. With FDA approval of the drug, Provention will pay the Rockville, Maryland-based biotech a $60 million milestone payment.

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