The confirmatory trial of one of the approved drugs, Pepaxto, was halted when data suggested it was associated with a higher mortality rate.
Zynlonta (loncastuximab tesirine-lpyl) was granted accelerated approval on April 23, 2021, for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma.
Approval was based on the study LOTIS-2 that showed the overall response rate was 48.3% (95% CI: 39.9, 56.7) with a complete response rate of 24.1% (95% CI: 17.4, 31.9) after a median follow-up of 7.3 months. The drug generated net sales of $3.8 million in the two months after the approval, according to ADC Therpeutics, the Swiss company that markets Zynlonta.
Pepaxto (melphalan flufenamide) was approved in February 2021 for use in combination with dexamethasone to treat adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody.Under the accelerated approval, the manufacturer, Oncopeptides AB, is required to conduct the OCEAN trial for follow-up safety and efficacy.
On July 28, the FDA announced that data from that trial was suggesting that treatment with Pepaxto led to an increased risk of death. Ongoing trials of the drug were suspended, and the FDA said it was “encouraging” healthcare professionals “to review patients’ progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments.”
The FDA announcement also said that patients being treated with the drug should discuss with their health care professional the risks and benefits of receiving Pepaxto. The drug regulatordirected healthcare professionals and patients to report anyadverse events associated with Pepaxto through the FDA’s MedWatch Adverse Event Reporting program.
The FDA granted accelerated approval and orphan drug designation to Ukoniq (umbralisib) in February 2021 for marginal zone lymphoma (MZL) and follicular lymphoma (FL). Approval was based on two single-arm cohorts of a multicenter multi-cohort trial, UTX-TGR-205 showing patients with MZL had an overall response rate of 49% with 16% achieving complete responses.Additionally, patients with FL had an overall response rate of 43% with 3% achieving complete responses. Serious adverse reactions occurred in 18% of patients, with the most common being diarrhea-colitis and infection.