Dive Brief:
- Genmab's shares opened almost 25% down Monday on the Copenhagen stock exchange after news surfaced that partner Janssen was stopping combination studies of Genmab's Darzalex plus Janssen's anti-PD-1 antibody JNJ-63723283 in multiple myeloma.
- This news followed a data monitoring committee recommending that Genmab should stop its Phase 1b/2 study of Darzalex plus Roche's anti PD-L1 antibody Tecentriq in patients with previously treated non-small cell lung cancer. That advice was based on a lack of benefit and a numerical increase in deaths. Readouts had been expected in the second half of 2019.
- Janssen has an exclusive worldwide license to develop, manufacture and commercialize Darzalex. The company has contacted its partners carrying out other Darzalex and anti-PD-1/PD-L1 combination studies regarding enrollment and dosing while the data is investigated.
Dive Insight:
The news that the CALLISTO/LUC2001 study of Genmab's Darzalex (daratumumab) plus Tecentriq (atezolizumab) was being stopped because of lack of benefit in the combination treatment arm over Tecentriq alone in non-small lung cancer has had a serious knock-on effect for Genmab.
Aside the disappointment and cost implications of the failure of the combination, it has led to Janssen, a Johnson & Johnson company, pulling its study of daratumumab plus Janssen's anti-PD-1 antibody JNJ-63723283 in multiple myeloma.
"While we are disappointed that the studies will be discontinued, Genmab fully supports Janssen's decision as patient safety is paramount in drug development. We look forward to gaining a better understanding of the data upon further analysis," said Jan van de Winkel, CEO of Genmab, in a statement.
It could also have ripple effects for the concept of checkpoint inhibitors in combinations, an area that has already made some people wary.
Jefferies analyst Peter Welford suggests that the statement that "Janssen has contacted its partner companies conducting daratumumab and anti-PD-(L)1 combination studies to discuss ceasing enrollment and dosing of the combination while the data is being further investigated" could infer that Celgene's FUSION studies with Imfinzi (durvalumab) in multiple myeloma and Bristol-Myers Squibb's trials with Opdivo (nivolumab) in solid tumors may also be halted.
The Imfinzi/daratumumab study was placed on partial clinical hold last year alongside a number of other PD-1/PD-L1 combinations, including the Opdivo/daratumumab CheckMate-039 study.
Darzalex is approved in the U.S. and Europe for the treatment of multiple myeloma in combination with a number of different drugs. It was the first monoclonal antibody to receive Food and Drug Administration approval for this indication, and the first human CD38 monoclonal antibody to reach the market. Clinical trials for Darzalex are ongoing, including Phase 3 studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis, and the drug is also being assessed in NKT-cell lymphoma, myelodysplastic syndromes, and B- and T-acute lymphoblastic leukemia.
Genmab originally developed Darzalex and licensed it to Janssen in August 2012 in return for an upfront fee of $55 million, along with an $80 million investment and up to $1 billion in development, regulatory and sales milestones.