June 22, 2017
By Alex Keown, BioSpace.com Breaking News Staff
BOTHELL, Wash. – Two days after Seattle Genetics halted all trials of its acute myeloid leukemia (AML) treatment vadastuximab talirine due to trial deaths, the U.S. Food and Drug Administration (FDA) has weighed in by slapping a hold on the company’s Investigational New Drug Application.
Seattle Genetics reported the FDA’s move in a filing with the U.S. Securities and Exchange Commission. In the filing, the company said no clinical trials may resume under the IND until the FDA lifts the clinical hold.
On June 19, the company said it came to the decision to halt the trials following a review of unblinded data and a consultation with the Independent Monitoring Committee. Data from the vadastuximab talirine trial arm showed a higher rate of death, including fatal infection. Following that consultation, Seattle Genetics said it suspended the Phase III AML trial, as well as 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.
If Seattle Genetics hopes to move forward with vadastuximab talirine, the company will have to present a lot of supporting data demonstrating its safety. However, there are obviously hurdles to overcome. This week’s FDA clinical hold is the second one the regulatory agency has placed on vadastuximab talirine. In December the FDA placed a hold on two Phase I clinical trials following four fatalities. 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.”
The clinical hold will certainly hamper Seattle Genetics’ short-term revenue plans, particularly after the crash of a $2 billion deal with Immunomedics. The two companies had planned to develop IMMU-132, Immunomedics (IMMU)’ proprietary solid tumor therapy candidate, but that deal was challenged by Immunomedics’ investors who said the deal was not good for the company.
Following the company’s decision to place the trials on hold (and before the FDA’s action) Seattle Genetics Chief Executive Officer Clay Siegall attempted to look at some of the positives facing the company, including a Phase III trial of Adcetris as a frontline Hodgkin lymphoma therapy. But Adcetris may not be enough to satisfy some investors. Writing in Endpoints John Carroll said Siegall will likely be under some pressure to “diversify beyond Adcetris.”
On Tuesday, Siegall did say 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.
Shares of Seattle Genetics are trading at $63.57 as of 10:48 a.m.
