- A cancer medicine made by Washington-based biotech Seattle Genetics Inc. could soon become a standard component in a drug cocktail used to treat frontline advanced Hodgkin lymphoma, replacing a lung-damaging chemotherapy agent used for decades.
- Results from a study of Seattle Genetics' drug Adcetris were first unveiled in June and will be presented in full during a plenary session Sunday afternoon at the annual meeting of the American Society of Hematology.
- Combining Adcetris with three older chemotherapies significantly extended progression-free survival in previously untreated patients, when compared to a regimen of those same three drugs paired with a chemo agent known as bleomycin.
A type of targeted therapy known as an antibody drug conjugate, Adectris (brentuximab vedotin) is currently approved for use in four different indications. Revenues have risen steadily, totaling $79 million in the third quarter of this year.
The drug's success in a study called ECHELON-1 or E1, however, could help Seattle Genetics and its Japanese partner Takeda Pharmaceutical Co. Ltd. broaden the number of patients it is approved to treat and boost sales.
"E1 is the single largest opportunity of anything we have looked at with Adcetris," explained Seattle Genetics CEO Clay Siegall in an interview, comparing the addressable market for Adcetris in frontline Hodgkin lymphoma to the drug's existing, narrower indications.
Seattle Genetics has already submitted an application to the Food and Drug Administration for Adcetris to be used together with the chemotherapies doxorubicin, vinblastine and dacarbazine — a triplet commonly referred to as AVD. A decision is expected in the first half of 2018.
If approved, Adcetris plus AVD could change the standard of care for frontline Hodgkin lymphoma, which for more than 30 years has been a combination of AVD and bleomycin (together called ABVD).
First discovered as a potent therapy against the blood cancer in the late 1970s, ABVD has in one sense been a chemotherapy success story, says Siegall.
While effective, though, bleomycin causes pulmonary toxicity that can impact quality of life and, in rare cases, kill. Replacing bleomycin has therefore been a goal for cancer researchers for some time.
"We expect ABVD to cure about three-quarters of patients — which means, of course, that one quarter will not be cured," said Joseph Connors, lead study author and clinical director of the British Columbia Cancer Agency Centre for Lymphoid Cancer in Vancouver, Canada, in a statement.
ECHELON-1's results look convincing for swapping in Adcetris for bleomycin. "In this study we’ve been able to significantly reduce that rate of treatment failure," Connors explained. "If this new regimen is widely adopted, it will change first-line treatment of advanced [Hodgkin lymphoma]."
Data showed Adectris plus AVD reduced the risk of disease worsening, death or a non-complete response by 23%. On overall survival, benefit trended in favor of the Adcetris arm but was not significant at an interim analysis.
"One might have expected better results combining brentuximab vedotin with chemotherapy and in patients that have been untreated," said Anna Sureda, head of the hematology department and stem cell transplant program at the Institut Català d'Oncologia - Hospital Duran i Reynals, in an interview.
"But we have to acknowledge this decrease in alternative treatment in patients relapsing and we have more than 20% of the patients that don't have any event, death, progression or additional treatment."
Importantly, removing bleomycin lowered lung toxicity, which was reported in 2% of patients taking the Adcetris combo versus 7% receiving ABVD.
That improvement didn't come without drawbacks, however. Patients in the Adcetris group experienced higher rates of peripheral neuropathy and neutropenia, the latter of which can be managed with prophylactic growth factors like Amgen Inc.'s Neupogen (filgrastim). Such concurrent treatment could be added to Adcetris' label in the event of an approval, although that would drive up treatment cost.
Replacing bleomycin, a generic, with Adcetris would, of course, also make the combo pricier.
When Seattle Genetics first unveiled the results of ECHELON-1 in June, shares in the company fell by more than 10% — seemingly on disappointment that the combo didn't deliver a greater punch and increased some safety risks.
Siegall attributed that reaction to pressure from certain hedge funds and stood by the commercial and clinical benefit of the Adcetris combo.
"We now cure more patients and don't have the bleomycin," he said. "That is the crux of E1 and it's why we received a [breakthrough therapy designation], why we were awarded a plenary and have a New England Journal [of Medicine] article [coming out]."
Markets, however, did not appear convinced. Shares in Seattle Genetics declined by about 10% in initial trading Monday morning, before gaining back some of those losses.
Editor's note: This article has been updated to include comments from Dr. Anna Sureda and a reference to the stock market reaction Monday.