Seattle Genetics has landed its fifth approval for the drug Adcetris (brentuximab vedotin), for classical stage III or stage IV Hodgkin lymphoma. The indication is for use in combination with chemotherapy for previously untreated disease.
The U.S. Food and Drug Administration granted the approval after it received priority drug and breakthrough therapy designations. About half of the 8500 patients diagnosed annually in the United States are at stage III or IV.
Seattle Genetics reaped $30.7.6 million in sales of Adcetris in 2017 and some analysts predict that the fifth time’s the charm for driving that number to $1 billion and beyond. Despite that potential, the company’s shares were down 1.56 percent at Tuesday’s market close, trading at $54.86.
Takeda and Seattle Genetics partnered to develop the drug, with Takeda keeping commercial rights for all but the United States and Canada. Takeda has begun trial data submission to agencies covering its regions of the globe, starting with the European Medicines Agency in November 2017.
Adcetris is an antibody-based drug conjugate that has already been approved for classical Hodgkin lymphoma after relapse or after stem cell transplant with high progression or relapse risk, and for systemic or primary cutaneous anaplastic large cell lymphoma after failure of at least one regimen. The antibody is conjugated to a cell-disrupting agent and targets a lymphoma cell–specific protein.
Supporting the approval are findings from the phase 3 ECHELON-1 trial comparing Adcetris plus Adriamycin/vinblastine/dacarbazine (AVD) to bleomycin plus AVD (ABVD). The main finding was a 23 percent reduction vs ABVD in modified progression-free survival, defined as an event of disease progression, death or need for additional therapy, The 2-year modified progression-free survival rates were 82.1 percent in the Adcetris combination arm compared to 77.2 percent in the ABVD arm, or a 4.9 percentage point difference.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
The trial results were published in December 2017 in the New England Journal of Medicine, but the journal tacked on a hefty correction in March 2018. Among the many changes in the correction are updated median follow-up and P values.
This therapy offers newly diagnosed patients the first frontline treatment update since 1977, when the ABVD regimen became available. The company said in a statement that swapping in Adcetris for bleomycin effaces some of the potentially fatal bleomycin-related pulmonary toxicities, as well. Adcetris is not without toxicity and carries a boxed warning for an infection risk with a virus that can lead to fatal progressive multifocal encephalopathy.
Seattle Genetics CEO Clay Siegall said at last fall’s Society of Hematology Meeting that survival outcomes in the Adcetris combination arm are promising because they often “[lead] to cures” in Hodgkins lymphoma, although the overall survival outcome was not significant.
Findings from another trial suggest a separate if delayed solution to the bleomycin problem. The RATHL trial evaluated the effect of just dropping bleomycin from the ABVD regimen after a couple of cycles in good responders. The results showed considerably reduced pulmonary side effects in AVD group and similar, good survival between treatment arms.
This option and the modest progression-free survival gains may have left investors feeling less than inspired by this fifth approval, which also disappointed with its narrow labeling, excluding less-advanced disease. The Tuesday afternoon stock dip on the news lasted through Wednesday trading.
Photo:Waldemarus, Getty Images
