Affimed has halted work on two phase 1 trials of its lead T cell engager AFM11 for blood cancers after a death and two life-threatening events.
The adverse events were seen in both trials of the cancer immunotherapy, with the death occurring in a study involving patients with acute lymphoblastic leukemia (ALL) and the two life-threatening events seen a non-Hodgkin lymphoma (NHL) trial.
Heidelberg, Germany-based Affimed says the adverse events happened in patients taking AFM11 at the highest dose in both trials, which to date have enrolled 33 patients who have been treated with the drug. It also says there was some signs of clinical activity “in several patients.”
News of the regulatory action caused the biotech’s Nasdaq-listed shares to lose almost a third of their value premarket, clawing back some big gains made in August after the biotech agreed a $96 million upfront deal with Roche’s Genentech for its natural killer (NK) cell engager platform for cancer, plus $5 billion in potential milestones.
The NK cell engager programs are unaffected by the clinical hold, stresses Affimed. The drugs are designed to redirect innate and adaptive immune cells towards cancer cells and thereby orchestrate attacks on tumors.
For example, AFM13 is a bispecific antibody that binds to CD30 on tumor cells and to the NK cell receptor CD16A. That is a different approach than used for AFM11, which targets T cells through CD3 and bids to CD19 on tumors.
At the moment the only other program in Affimed’s T cell engager pipeline is AMV564, a CD33/CD3 bispecific in phase 1 for acute myeloid leukemia (AML) that is licensed to San Francisco biotech Amphivena.
Affimed hasn’t yet provided any further information on the adverse events but says it “will be working closely with the global health authorities, the safety monitoring committees, and the studies' clinical investigators to review the events, carefully assess all of the data and determine next steps for the AFM11 program.”
Shares in the company bumbled along at around the $2 mark for months ahead of the Genentech deal, which helped to drive them above $6 before gradually returning to around $4 in the following weeks. It currently has a market cap of around $290 million. It was down nearly 28% in pre-market trading this morning on the news.
Analysts at Jefferies said in a note to clients this morning: “We believe these SAEs are isolated to AFMD's [Affimed’s] AFM11 CD3-engager program; we do not see much, if any, readthrough to AFMD's NK (CD16A) programs. CD3 causes rapid T cell proliferation, which can lead to CRS and toxicities including neurotox. The SAEs w/ AFM11 highlight the sensitive safety threshold/boundary in both ALL and NHL w/ the CD19 and CD3 targets.
“Since these toxicities have been observed w/ Blincyto, Yescata, and Kymriah , all approved, we believe AFM11 may still rebound and succeed; though, AFMD will need to do add'l work, likely with dosing/patient selection, to better understand safety/efficacy limitations. And, for eventual approval and commercial success, AFMD will have to demonstrate differentiation and superior risk/benefit profile vs approved programs.”
Editor's note: This story incorrectly stated that the FDA had placed the trials on clinical hold - it was Affimed who put the trials on a voluntary hold.