Seattle Genetics Says Adcetris Sets New Standard In Frontline Lymphoma
Executive Summary
The market for a new FDA-approved indication in frontline classical Hodgkin lymphoma could be worth $650m to $750m, some analysts say.
Seattle Genetics Inc. sees its antibody drug conjugate Adcetris (brentuximab vedotin) as setting a new standard of care in the frontline treatment of classical Hodgkin lymphoma following US FDA approval for use with chemotherapy in previously untreated Stage III and Stage IV disease on March 20.
Adcetris, which is partnered ex-US with Takeda Pharmaceutical Co. Ltd., combines an antibody with the cytotoxic payload of the microtubule-disrupting agent monomethyl auristatin E (MMAE) targeted at CD30 on lymphoma cells. The drug's new indication means more than 4,000 patients are eligible for treatment with the ADC, since roughly 8,500 new cases of Hodgkin lymphoma are diagnosed in the US each year, about half of which are Stage III/IV.
Adcetris was FDA approved prior to March 20 for relapsed Hodgkin lymphoma, Hodgkin lymphoma after stem cell transplant in patients at high risk of relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after failure of other treatment, and primary cutaneous ALCL after failure of other treatment. (Also see "Pivotal ALCANZA Trial Secures Adcetris' Position in Cutaneous Lymphoma" - Scrip, 7 Dec, 2016.)
Adcetris had global sales of $600m in 2017. The company has been under pressure to flesh out the franchise following the failure and termination of its leukemia drug candidate vadastuximab talirine (SGN-CD33A) in mid-2017. (Also see "A CASCADE Of Trouble For Seattle Genetics' AML Drug SGN-CD33A" - Scrip, 19 Jun, 2017.)
The frontline Hodgkin lymphoma approval marks the drug's fifth approved indication in the US. Seattle Genetics is planning another two label expansions based on ongoing Phase III studies. One study called ECHELON-2 tests Adcetris with the chemotherapy combination of cyclophosphamide, doxorubicin and prednisone in frontline peripheral T-cell lymphoma, also called mature T-cell lymphoma, with results due in the fourth quarter. The other study – CheckMate 812 – tests Adcetris with Bristol-Myers Squibb Co.'s PD-1 inhibitor Opdivo (nivolumab) for relapsed Hodgkin lymphoma and has a primary completion date of November 2020.
"We are really excited to get [to] seven out of seven," CEO Clay Siegall commented to Scrip.
Bid To Become Standard Of Care
Adcetris had a breakthrough therapy designation and priority review status for the latest filing and approval came ahead of the May 1 user fee date.
Currently, the standard of care for Stage III/IV Hodgkin lymphoma is the four-drug 'ABVD' combination of Pfizer Inc.'s Adriamycin (doxorubicin), bleomycin, vinblastine and dacarbazine. But bleomycin is highly toxic, carrying a risk of death due to severe pulmonary distress, and doctors have long wanted to get rid of it, Siegall explained.
But the standard of care in frontline classical Hodgkin lymphoma is now set to change after 40 years with no progress, Siegall maintained. (Also see "Seattle Genetics Looking To Improve, Replace Standards Of Care" - Scrip, 30 Jan, 2018.)
Approval was supported by the ECHELON-1 study comparing Adcetris with Adriamycin, vinblastine and dacarbazine against chemotherapy alone in 1,334 previously untreated patients with Stage III or IV classical Hodgkin lymphoma (cHL). The primary endpoint was modified progression-free survival, that is the time to progression or death. In the Adcetris/AVD arm, 18% progressed versus 22% for ABVD, a 23% improvement (p=0.035).
Side effects in the study included peripheral neuropathy and neutropenia, which occurred in 91% of patients in the Adcetris arm, and febrile neutropenia (19%).
"Preventative treatment with G-CSF, a growth factor for the bone marrow to produce white blood cells, is recommended with Adcetris plus chemotherapy for the first-line treatment of Stage III or IV cHL," FDA noted in a statement about the approval.
Other side effects include nausea, fatigue, constipation and diarrhea.
Adcetris labeling carries a boxed warning for risk of John Cunningham virus infection, which can cause progressive multifocal leukoencephalopathy, a life-threatening brain infection.
Market Value
William Blair analyst Andy Hsieh said in a March 20 note that the approval provides Adcetris with an additional addressable market of roughly $650m-$700m in the US.
"There has been some skepticism among the investment community regarding the adoption of the Adcetris-containing regimen in the Hodgkin lymphoma setting, due to the perceived 'marginal' efficacy benefit. We do not agree with this assessment as Adcetris provides both an efficacy and safety improvement over the standard of care," Hsieh said.
"Moreover, given that the majority of Hodgkin lymphoma patients are in their 20s and 30s, achieving the more stringent modified progression-free endpoint will most likely lead to long-term remissions, thereby providing significant quality-of-life and societal benefits. On the safety side, the elimination of bleomycin removes the potential for young patients to suffer from permanent lung damage, a side effect that is unpredictable and difficult to manage," he added.
The market for CD30+ T-cell lymphomas being tested in ECHELON-2 is worth another $300m to $500m in the US, Hsieh estimated.