Bracing for patent losses on its cornerstone product Darzalex, Genmab has bet its future on three cancer programs that will deliver pivotal readouts in quick succession.
Genmab faces an unprecedented situation. Nearing the loss of a revenue source that accounts for 90% of its sales, the company is approaching arguably the largest cliff that any company has ever faced in the pharma industry, Tahamtan Ahmadi, chief medical officer and head of experimental medicines at Genmab, told BioSpace.
And a series of readouts this quarter could foreshadow whether the company will grow beyond the cliff. Two clinical wins earlier this month have set the stage with two more readouts still expected by the end of the year.
Today, Genmab relies heavily on royalties from Darzalex, its Johnson & Johnson–partnered cancer drug whose U.S. patents expire in 2029. Genmab lost cases that could have softened the drop in revenues as these patents run out, creating a steep cliff.
The biotech’s Darzalex revenues could fall from about $3.3 billion in 2028 to under $1 billion by 2031, and to roughly zero by 2032, Raghuram Selvaraju, managing director of Healthcare Equity Research at H.C. Wainwright, told BioSpace by email. Despite that, the analyst believes Genmab can emerge from the trough years of 2029 and 2030 in a strong position.
“We think Genmab has more than enough horsepower under the hood to overcome the almost total loss of revenue from Darzalex,” Selvaraju said. “Genmab’s ability to weather this challenge depends on three wholly owned or partnered oncology assets.”
The company recently shared positive data on two of the three assets. In the first week of October, Genmab reported Phase 3 findings from the AbbVie-partnered Epkinly in first-line lymphoma that analysts said could potentially set “the new standard of care” in this indication and posted “durable and clinically meaningful” Phase 2 results for the antibody-drug conjugate (ADC) rinatabart sesutecan (Rina-S) in ovarian cancer. Genmab expects Phase 3 Rina-S data this year, but Selvaraju now sees data on the third asset, petosemtamab, as the only “binary event risk.”
Genmab’s big bet
Genmab acquired petosemtamab, a bispecific antibody targeting EGFR and LGR5, last year in its $8 billion takeover of Merus. Among Genmab’s three key assets, “petosemtamab matters the most,” Selvaraju said. That view reflects a sales ramp that could make the bispecific a blockbuster by 2029, the year Darzalex’s U.S. patents expire, as well as possible launches in additional indications.
The lead indication for petosemtamab is head and neck squamous cell carcinoma (HNSCC). Genmab expects to share results from the Phase 3 LiGeR-HN1 trial in patients with first-line HNSCC by the end of the year. In May 2025, Merus reported a 63% overall response rate (ORR) in a Phase 2 study, far surpassing the 19% Merck’s Keytruda achieved in the Phase 3 KEYNOTE-048 study—a result noted by both Selvaraju and Genmab’s Ahmadi.
Achieving a 40-point or greater improvement in ORR, a co-primary endpoint in the Phase 3 trial, “would support accelerated approval and fast uptake,” Selvaraju said. Beyond that, Genmab would need to show that the increased response rate translates into improved progression-free (PFS) and overall survival (OS), the latter the study’s other primary outcome measure. PFS is a secondary endpoint. Ahmadi outlined how ORR could predict PFS and OS.
“If you have a dramatic ORR difference, and the durability is good, it almost has to translate into a statistical or near-statistical PFS difference. And then, of course, it has to translate into separation in the OS curves, because otherwise it would have a safety liability,” the CMO said.
ADC nears key readout
LiGeR-HN1 is one of two remaining Phase 3 readouts for Genmab assets this year. The biotech also plans to share data from RAINFOL-02, which is testing its FRα-directed ADC Rina-S in platinum-resistant ovarian cancer (PROC).
The readout is “relatively risk-mitigated because of the positive Phase 1/2 RAINFOL-01 data in PROC,” Selvaraju said. The Phase 1/2 clinical trial linked Rina-S to a median PFS of 9.5 months, hitting a secondary endpoint. AbbVie’s rival FRα-directed ADC Elahere achieved a median PFS of 5.6 months in the Phase 3 MIRASOL trial.
Chemotherapy is the control treatment in RAINFOL-02. Based on the earlier data on Rina-S and chemotherapy, the RAINFOL-02 readout could be “very positive on PFS and potentially even on OS,” Ahmadi said. A positive PFS outcome—the trial’s primary endpoint—is “highly likely, with interim OS success (a higher bar) being possible in an upside scenario,” Guggenheim Securities analysts said in an Oct. 4 note to investors.
Analysts are also looking for Genmab to replicate the breadth of efficacy seen in the Phase 1/2 trial, when the biotech reported activity in patients with low or no FRα expression. Securing a label across FRα levels would double the addressable population compared to Elahere, Selvaraju said. The analyst sees the FRα labeling terms as the variable that will determine the slope of the ramp for Rina-S sales.
The competitive landscape amplifies the value of launching and growing Rina-S quickly. Rina-S is part of a wave of ADCs that use topoisomerase-1 (TOPO-1) inhibitors to treat ovarian cancer. Once a patient progresses after receiving one TOPO-1 ADC, they are unlikely to benefit from another treatment with the same payload, Ahmadi said. The importance of becoming the first-choice TOPO-1 ADC is encouraging speed and secrecy.
“We are not pre-announcing these studies anymore. We basically make them public at the time the first patient gets dosed,” Ahmadi said. “It is competitive and everybody’s looking over everybody’s shoulder and copying everybody’s strategy.”
Competing commercially
Victories in LiGeR-HN1 and RAINFOL-02 would establish petosemtamab and Rina-S alongside Epkinly as drugs that can power Genmab through and beyond the Darzalex cliff. Yet positive data will only be a step toward the sales Genmab needs to mitigate the loss of royalties from the drug. Genmab also needs to achieve regulatory and commercial successes, and it is facing those challenges solo.
The market “is still a little bit skeptical” about Genmab’s prospects in this respect, Ahmadi acknowledged. Genmab is entering “a hypercompetitive environment” and biotechs always face questions about whether they can compete commercially with larger rivals, he added.
Ahmadi sees Epkinly’s success as evidence that Genmab can rise to the challenge. Working with AbbVie, Genmab has turned Epkinly into a challenger to Roche, a company that “owned” the market for 25 years with Polivy and Rituxan, Ahmadi said. Through that process, Genmab has built commercial and operational capabilities that could benefit petosemtamab and Rina-S.
“We’ve been beating [Roche’s Columvi] quarter for quarter for quarter,” Ahmadi said. “I think that is a little bit unappreciated: how good we have become in running these trials, speeding up development, and how competitive we already are as a company.”
