Seattle Geneticshas submitted a supplemental Biologics License Application (BLA) to the US Food and Drug Administration (FDA) based on data from the phase 3 ALCANZA trial and two phase 2 investigator-sponsored trials of Adcetris (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL). Adcetris is currently not approved for the treatment of CTCL.
“The submission of the supplemental BLA requesting label expansion for Adcetris as a treatment in CTCL patients who require systemic therapy is an important milestone. CTCL is an incurable and disfiguring disease in need of new therapeutic options, particularly those that achieve durable responses,” said Jonathan Drachman, M.D., chief medical officer and executive vice president, Research and Development of Seattle Genetics. “Results from the phase 3 ALCANZA trial demonstrated that CTCL patients treated with Adcetris had superior outcomes across all primary and secondary endpoints compared to patients in the control arm who were treated with either methotrexate or bexarotene standard of care agents. In addition to the ALCANZA results, data from two investigator-sponsored trials also support Adcetris use in this disease setting. We believe these data are clinically meaningful and support a label expansion for Adcetris in CTCL, which would be the fourth indication for this program.”
In November 2016, based on preliminary analysis of ALCANZA, the FDA granted Adcetris Breakthrough Therapy Designation (BTD) for the treatment of patients with CD30-expressing mycosis fungoides and primary cutaneous anaplastic large cell lymphoma who require systemic therapy and have received one prior systemic therapy. These represent the most common subtypes of CTCL. Based on discussions with the FDA following the BTD, additional data from investigator-sponsored phase 2 trials have been incorporated into the supplemental BLA to support the potential for a broader label in CTCL.
The supplemental BLA is primarily based on positive results from a phase 3 trial called ALCANZA that were presented at the 58th American Society of Hematology (ASH) annual meeting in December 2016 and published in the Lancet in June 2017. Results from the ALCANZA trial in 128 CTCL patients requiring systemic therapy included: The trial achieved its primary endpoint with the Adcetris treatment arm demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) versus the control arm as assessed by an independent review facility. ORR4, as assessed by Global Response Score, was 56.3 percent in the Adcetris arm compared to 12.5 percent in the control arm (p-value <0.0001).
Key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment (Skindex-29), were all highly statistically significant in favor of the Adcetris arm. The safety profile associated with Adcetris from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events of any grade include: peripheral neuropathy, nausea, diarrhea, fatigue, vomiting, alopecia, pruritis, pyrexia, decreased appetite and hypertriglyceridemia.