FDA Places Clinical Hold on AML Drug Co-Developed by Johnson & Johnson and Genmab A/S

FDA Places Clinical Hold on AML Drug Co-Developed by Johnson & Johnson and Genmab September 19, 2016
By Mark Terry, BioSpace.com Breaking News Staff

Johnson & Johnson has indicated that its acute myeloid leukemia (AML) drug, JNJ-63709178, has been put on clinical hold because of serious side effects.

The drug targets both CD3 and CD123 and was part of a Phase I, First-in-Human, Open-Label, Dose Escalation Study. As part 1, dose escalation, patients received intravenous infusions of the drug at a dose of 2 microgram/kilogram. Each subsequent cohort was to receive intravenous infusions at an increased dose level, which would continue until the maximum tolerated dose was identified or all planned doses were administered. They were to receive the IV infusion once every two weeks.

The CD3 complex is a group of proteins on the surface of T-cells. CD123 is a tumor-associated antigen (TAA) that is overexpressed on the surface of some tumor cells. The idea of JNJ-63709178 is that the bispecific antibody will simultaneously bind to both CD3-expressing T-cells and CD123-expressing cancer cells. The crosslink will hopefully result in a potent destruction of tumors cells that express CD123.

No information regarding how far in the study patients were, or what specific adverse effects were observed. A company spokesperson said, “Janssen R&D temporarily suspended the study on August 8. We’re working with the FDA now to address recommended changes to the study. At this point, we don’t have any additional details to share. We’re hoping to resume the study with appropriate guidance from the FDA.”

The drug is a bispecific antibody developed via a collaboration between J&J company Janssen and Danish company Genmab A/S utilizing Genmab’s DuoBody technology. The two companies entered into a licensing agreement in July 2012 to use the DuoBody platform to produce and develop bispecific antibodies. The deal called for Janssen to create up to 20 DuoBody products. The first was JNJ-61186372, which targeted EGFR and cMet, two validated targets for cancer.

In July, the U.S. Food and Drug Administration (FDA) granted Genmab and Janssen’s Darzalex (daratumumab) Breakthrough therapy designation. The drug is a mononclonal antibody being evaluated to treat multiple myeloma in combination with standard of care treatments. The drug is being evaluated in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone.

“This is the second time daratumumab has earned the distinction of a Breakthrough therapy designation,” Jan van de Winkel, chief executive officer of Genmab, said in a statement in July. “We are pleased that the FDA continues to recognize the potential of daratumumab to help patients with multiple myeloma. We continue to work with our strategic partner Janssen and the regulatory authorities to advance daratumumab to bring this treatment to more patients suffering from multiple myelomas as quickly as possible.”

The drug is also being studied in other malignant and pre-malignant diseases in which CD38 is expressed. These include smoldering myeloma, non-Hodgkin’s lymphoma, and solid tumors.

Back to news