Visilizumab

Janssen's recent approval ask for talquetamab follows FDA green lights for two of the company's other myeloma treatments in 2022. On the heels of its FDA submission, Johnson & Johnson is unveiling results used to woo regulators on its bispecific antibody in multiple myeloma patients in dire need of successful treatment.  The new phase 2 data, released Monday at the American Society of Hematology annual meeting, showed that among patients who received a median of five prior lines of treatment, J&J’s talquetamab reached an overall response rate of 74.1% when administered weekly. The response rate dropped slightly to 73.1% when the dose was doubled but administered every two weeks. The company says that a nine-month median duration of response was achieved at both dose levels.  In more than a third of patients treated with the weekly, subcutaneous 0.4-mg/kg dose, talquetamab reached complete remission, while 32.4% of patients treated with 0.8 mg/kg every two weeks hit such a mark. The median progression-free survival in patients treated with the weekly dose was 7.5 months with a median follow-up of just under 15 months. J&J says the PFS in patients treated every two weeks was not yet mature due to a shorter follow-up time.  Cytokine release syndrome, a reaction to an overstimulation of the immune system, was prevalent in treated patients. Nearly 80% of patients treated weekly experienced the syndrome compared to 72.4% in patients treated every two weeks. And, while the vast majority of the cases were not severe, 2.1% of patients treated weekly experienced a grade 3 or 4 reaction. The majority of severe side effects came from cases of depleted white blood cells and low platelet count. Ultimately, nearly 5% of patients treated weekly ended treatment due to adverse events, and 14.7% had their dose reduced.  The new findings are an example of J&J looking to pad the stats on yet another potential instrument in its collection of myeloma treatments. The submission to the FDA late last week follows two approvals handed to the massive pharma from U.S. regulators over the course of the year. In February, the FDA approved J&J and Legend’s entry into the CAR-T race with the two’s B-cell maturation antigen-targeting Carvykti. And, less than two months ago, regulators gave an accelerated nod to J&J’s BCMA-focused bispecific Tecvayli.  Talquetamab takes on new targets beyond BCMA, homing in on both GPRC5D and CD3. Some of the treatments that participating patients failed to respond to include a proteasome inhibitor, an immunomodulatory agent and an anti-CD3 antibody. In a smaller cohort of patients that previously received T-cell direction therapy, talquetamab was found to be more effective in patients who didn’t respond to prior CAR-T therapy compared to patients who received a T-cell-focused bispecific antibody.  “Talquetamab is [a] testament to our ongoing commitment to deliver novel treatment approaches for patients who have exhausted all other options,” said Edmond Chan, M.D., hematology therapeutic lead in Europe, the Middle East and Africa, said in a release.  After receiving orphan-drug designation by both U.S. and European regulators in 2021, talquetamab nabbed breakthrough designation from the FDA in June 2022. A deadline for regulators to decide on the drug will become clear once they accept J&J’s submission application. 

The FDA has approved Provention Bio’s Biologics License Application for intravenous antibody TZIELD (teplizumab-mzwv) to delay stage 3, Type 1 Diabetes, making it the first disease-modifying drug indicated to slow disease progression. The regulatory nod, announced by Provention Thursday, covers adult patients and children aged 8 years old and above with stage 2 T1D. Delaying the onset of stage 3 disease can lessen the patient’s risk of developing diabetic ketoacidosis, an often life-threatening complication, and reduce the stress, fear and anxiety associated with disease progression. Ashleigh Palmer, co-founder and CEO of Provention, said in a statement that slowing T1D progression buys a patient and their families more time to prepare for the additional burden posed by stage 3 disease. Dr. Eleanor Ramos, the company’s chief medical officer, added that at stage 3, patients may need, in just one year, “1,460 finger sticks to check blood glucose levels, around 1,110 insulin injections” and experience more than 120 hypoglycemic episodes on average. TZIELD’s approval affords some patients more time to live without these burdens and complications. TZIELD is an anti-CD3 antibody that delays the onset of stage 3 T1D by deactivating lymphocytes that have become autoreactive against pancreatic beta cells. In the randomized, placebo-controlled, double-blinded TN-10 study, TZIELD cut the risk of progressing to stage 3 T1D by nearly 60%, with a hazard ratio estimate of 0.41 and a p-value of 0.0066. Data from TN-10 supported Thursday’s approval. The Long Journey to Approval TZIELD has had a long road to approval. In July last year, the FDA flagged issues with the drug’s pharmacokinetic pro potential product quality. After addressing these issues, Provention resubmitted its BLA for TZIELD, which the FDA accepted in March and set a target action date of Aug. 17. However, in July, the New Jersey-based biotech received word that the verdict would be delayed another three months following the FDA’s request for additional information, which it would then consider a major amendment to the application. The extension allows the agency ample time to review the new data. Despite the speedbumps, Provention was confident its drug would prevail. In September, the company announced the receipt of a $125 million loan from Hercules Capital. The money would be earmarked for launching activities and infrastructure of TZIELD, Provention told BioSpace at the time. To further support the drug, Provention signed a co-promotion agreement with Sanofi in October. Under the terms of the deal, Provention retains all rights to TZIELD and will remain responsible for all R&D, as well as pharmacovigilance, production quality and safety activities. Meanwhile, Sanofi will have an exclusive right to the first negotiation for an in-license agreement over TZIELD worldwide, which runs until June 2023.