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Seattle Genetics/Takeda’s Adcetris, likely to get label expansion

Seattle Genetics (NASDAQ:SGEN) and Takeda Pharmaceutical’s (TYO:4502) Adcetris (brentuximab vedotin) will likely get a Hodgkin’s lymphoma (HL) label expansion from the FDA based on results of the AETHERA study, experts said.

The Phase III trial’s (NCT01100502) positive results on the primary endpoint of progressionfree survival (PFS) in patients who are at high risk of relapse following autologous stem cell transplant (autoSCT) make approval likely, they said. The current practice is not to treat high-risk patients and to wait for them to relapse before receiving allogeneic SCT (alloSCT), some experts said, noting that alloSCT is a difficult procedure to undergo. As such, an expert added, forestalling relapse is valuable for those patients.

Topline results of the study were presented at the American Society of Hematology’s (ASH’s) 2014 annual meeting in December, and this news service reported 11 September 2014 that AETHERA had potential to expand the Adcetris label in the US and EU.

Seattle Genetics did not respond to requests for comment.

Strong uptake prospects in postautologous transplant, high-risk patients

Label expansion likely

The AETHERA data will likely drive an expansion of Adcetris’ label in HL to include use in the consolidative setting post-autoSCT and result in widespread use of the drug, said Dr David Peace, professor, medicine, University of Illinois College of Medicine, Chicago; Dr Nam Dang, deputy chief, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville; and Dr Elizabeth Budde, assistant professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California. Median PFS by independent review was 43 months for the Adcetris group and 24 months for the placebo group, according to an 18 February Seattle Genetics press release.

The data looks compelling and is likely to lead to FDA approval, said Dr David Aboulafia, section head, Department of Hematology/Oncology, Virginia Mason Clinic, Seattle, Washington. On the other hand, he said, it raises the question of how to sequence the drug because a lot of the patients get Adcetris before transplant, but for high-risk patients who have not received it pre-transplant, it will likely become a post-transplant maintenance standard of care. This news service reported 11 September 2014 that even if AETHERA was positive for PFS and OS, the results may not apply to patients getting Adcetris in first- or second-line therapy, and while the drug is not routinely used in those settings, that could change going forward. The study excluded patients previously treated with Adcetris, according to

The FDA has accepted Seattle Genetics’ sBLA based on the AETHERA data, the company said in a 20 April press release. Currently, the drug has accelerated approval for HL patients after failure of autoSCT or patients who are not autoSCT candidates and have failed at least two prior multi-agent chemotherapy regimens, as well as for systemic anaplastic large-cell lymphoma (ALCL) after failure of at least one multi-agent chemotherapy regimen.

AETHERA enrolled high-risk patients with a highrisk disease, noted Dr Nishitha Reddy, associate professor, medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee. With HL curable in 80-85% of patients, those being taken to transplant represent a small percentage, while those meeting the criteria for high-risk are an even small percentage, maybe 7-8%.

The study included patients considered at highrisk of residual HL post-autoSCT, including 196 refractory to frontline therapy, 107 who had relapsed less than 12 months after frontline therapy and 26 who had relapsed at least 12 months after frontline therapy with extranodal disease, according to published results (Moskowitz, et al. Lancet. 2015 May 9;385(9980):1853-62). The current practice is not to do anything for those patients, and to simply wait until they relapse before giving them allogeneic stem cell transplant (alloSCT), noted Reddy and Budde. Yet, alloSCT after autoSCT is not a trivial procedure and is very hard on patients, they added. Frontline HL treatments include radiation and chemotherapy-combination regimens like doxorubicin/bleomycin/vinblastine/dacarbazine (ABVD) and bleomycin/etoposide/doxorubicin/ cyclophosphamide/vincristine/procarbazine (BEACOPP), according to the American Society of Clinical Oncology.

Targeted population small, usually does not receive treatment

It would be very helpful to be able to delay alloSCT by a couple of years, Reddy said. Watching and waiting after autoSCT without maintenance can be nerve-wracking for patients, so Adcetris maintenance therapy will definitely benefit them, Budde said.

Given Adcetris’ extensive use in HL and ALCL and her center’s ample experience with the administration and side-effect profile of the drug, Budde said she saw herself giving it widely in the post-autoSCT high-risk setting. Approval in that setting will also likely change practice in the sense that community oncologists will be more comfortable giving the drug, Dang said, explaining that academic oncologists such as he tend to be more liberal in their usage of drugs like Adcetris.

In AETHERA, the most frequent adverse events included peripheral sensory neuropathy and neutropenia, according to the results.

Yet, usage in the community setting may not be so likely because most oncologists who deal with post-transplant relapses are more or less in the academic setting, Reddy said, adding that she did not foresee a huge increase in Adcetris’ usage following FDA approval of the label expansion.

AETHERA’s lack of OS difference between the arms, could be due to patients in the placebo arm crossing over to receive Adcetris, Dang noted. This news service reported 11 September 2014 that OS improvement may be needed for doctors to use Adcetris in post-transplant maintenance or for the drug to change practice, though HL is a difficult disease in which to show OS benefit. However, commenting on the most recent data, Budde said the goal of post-transplant maintenance is to keep patients in remission, making PFS a more important endpoint.

A pre-specified analysis showed no statistically significant difference in OS between the two arms, according to a 29 September 2014 Seattle Genetics and Takeda press release, but a further analysis for OS is expected in 2016. For the pooled study population at 24 months, the Kaplan-Meier estimate for OS was 88%, according to the ASH abstract (abstract no. 673).

Seattle Genetics’ market cap is USD 5.8bn.

August 3, 2015

Alaric DeArment


New York

Alaric DeArment covers cancer drugs and vaccines for BioPharm Insight. Previously, he was associate editor at Drug Store News, covering retail and specialty pharmacy, pharmaceuticals, biologics and regulatory affairs. A native of Seattle, he graduated with honors with a bachelor degree in journalism from Ball State University and also lived in China from 2001-2004.


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