Vadastuximab talirine

June 26, 2017 By Mark Terry , BioSpace.com Breaking News Staff Seattle Genetics and Takeda Pharmaceutical Company announced positive results from the Phase III ECHELON-1 clinical trial in previously untreated advanced classical Hodgkin lymphoma. The trial evaluated Adcetris (brentuximab vedotin) plus Adriamycin, vinblastine, decarbazine versus standard of care, Adriamycin, bleomycin, vinblastine, dacarbazine (ABVD). One of the issues with ABVD is bleomycin, which has been associated with higher rates of lung toxicity. In the trial, the Adcetris-combination group showed a statistically significant improvement in modified PFS versus the control group. The two-year modified PFS rate for the Adcetris-combo group was 82.1 percent compared to the control arm’s 77.2 percent. Perhaps more importantly, the Adcetris-control group appeared to have a better safety pro the control group, although there was an increased incidence of febrile neutropenia and peripheral neuropathy. John Carroll, writing for Endpoints News , noted , “The Adcetris combo hit a two-year modified PFS rate of 82.1 percent compared to 77.2 percent in the control arm—a 4.9 point, or 6 percent, improvement. That’s statistically significant, but not the wider, double-digit margin that the bulls have been looking for, according to a recent deep dive on this subject from Leerink. Analysts there have noted that without a 10-percent-plus margin in its favor, payers may just stick with the cheaper standard. The difference could amount to hundreds of millions of dollars for Seattle Genetics by 2025.” Investors were closely watching the results of this trial after Seattle Genetics abandoned a $2 billion deal with Immunomedics after shareholders tossed out Immunomedics’ top executives earlier this year. In February, Seattle Genetics agreed to pay $250 million upfront to license a drug for solid tumors from Immunomedics ( IMMU ). Future milestone and royalty payments could have hit $2 billion. But after the proxy challenge to board members of Immunomedics, a restraining order was placed on the deal and the two companies agreed to terminate the license for IMMU-132. The company also recently halted a Phase III trial of SGN-CD33A (vadastuximab talirine) in acute myeloid leukemia after higher rates of death, including fatal infections. Although today’s announcement is good news, it’s probably not a slam-dunk. Seattle Genetics plans to first-line treatment approval for Hodgkin’s lymphoma with the U.S. Food and Drug Administration soon. The company indicates it will likely charge $100,000 to $120,000 for the average Hodgkin patient. Matthew Herper, writing for Forbes , notes that while Seattle Genetics stock grew dramatically last year, it has only grown 17 percent this year, which is about half of the biotech indices. And shares, he writes, “sank last week after studies of an experimental drug, vadastuximab talirine, were stopped due to an elevated death rate with the treatment.” And there is likely to be some nitpicking over the trial design and the company’s use of modified PFS. John Carroll writes, “Rather than stick with tracking the time until disease progression, researchers modified the endpoint to include the use of an additional therapy for patients who had a ‘certain lack of response,’ says the CEO ( Clay Siegall ), who added that that is a simplistic definition. If approved, says Siegall, this would be Adcetris’ 5th OK, with earlier expansions helping to continue to widen the market for their drug.” “We think Adcetris has an excellent chance of being a billion-dollar drug in the U.S.,” Siegall told Carroll. Maybe. Approval seems likely, but whether insurers will opt for it over standard of care is an open question. Seattle Genetics is currently trading for $57.

June 19, 2017 By Alex Keown , BioSpace.com Breaking News Staff BOTHELL, Wash. – Seattle Genetics has halted all clinical trials of its vadastuximab talirine due to higher incidents of death associated with the treatment for acute myeloid leukemia (AML) patients. This is the second time the treatment has been halted due to fatalities. The news caused shares of Seattle Genetics to fall more than 11 percent in premarket trading to $57.25, down from $64.52. This morning, Seattle Genetics said the decision to halt the anticipated Phase III Cascade trial came after consulting with the Independent Monitoring Committee and examining unblinded trial data that showed a higher rate of death, including fatal infection, in the vadastuximab talirine trial arm. As a result, Seattle Genetics said it was suspending all clinical trials associated with vadastuximab talirine, including the ongoing phase I/II clinical trial in frontline high risk myelodysplastic syndrome (MDS). Vadastuximab talirine (SGN-CD33A; 33A) is a novel investigational ADC (antibody drug conjugate) targeted to CD33. An antibody-drug conjugate (ADC), it is designed to be stable in the bloodstream. Clay Siegall , president and chief executive officer of Seattle Genetics, said the data was both unexpected and disappointing. Siegall said the company will closely review the data and consult with the U.S. Food and Drug Administration regarding the potential future of vadastuximab talirine. Seattle Genetics’ decision came only a few months after the U.S. Food and Drug Administration lifted a hold on two Phase I clinical trials for vadastuximab talirine. The FDA slapped a hold on that trial in December after four patients died. In total six patients in that trial were shown to have hepatotoxicity, including several cases of veno-occlusive disease. Two additional Phase I trials also received a partial hold at the time. The clinical hold was lifted in March following an intense examination of trial data and the establishment of new safety protocol amendments. While the company resumed the two Phase I trials, Seattle Genetics opted to terminate a Phase I/II trial of vadastuximab talirine monotherapy in pre- and post-allogeneic transplant AML patients due to “he challenges of developing therapies in this specific setting.” Siegall tried to put a positive spin on the news by touting other drugs in the company’s pipeline. Siegall said the company is looking to a Phase III trial of Adcetris as a frontline Hodgkin lymphoma therapy. He also said the company is “on track” to advance enfortumab vedotin into a pivotal trial in metastatic urothelial cancer in the second half of 2017 under Seattle Genetics’ collaborative deal with Astellas. The halting of the vadastuximab talirine trials will certainly be a blow to the company that is still trying to shake off the crashing of a $2 billion deal with Immunomedics ( IMMU ). The two companies had planned to develop IMMU-132, Immunomedics’ proprietary solid tumor therapy candidate, but that deal was challenged by Immunomedics’ investors who said the deal was not good for the company.