Johnson & Johnson currently boasts one of the largest lineups of multiple myeloma products. Since its first FDA approval of a drug for this type of blood cancer a decade ago, the pharmaceutical giant has expanded in this space with additional drugs representing different modalities. To Joshua Bauml, vice president, lung cancer area stronghold leader at J&J, the company’s experience in multiple myeloma is a blueprint for its strategy in lung cancer.
“Look at what we’ve done in multiple myeloma,” Bauml said. “We started an area where there was nothing and we’ve really built out a pipeline. And that’s exactly what we intend to do in lung cancer.”
J&J’s multiple myeloma portfolio is anchored by Darzalex. Today, that drug is not only J&J’s top-selling cancer product, it’s the company’s top drug overall. J&J also has blockbuster expectations for its lung cancer drug, Rybrevant. Lung cancer is one of J&J’s areas of focus, what the company calls “disease strongholds.” In an interview during the annual meeting of the American Society of Clinical Oncology in Chicago, Bauml laid out J&J’s strategy for Rybrevant.
Some cases of lung cancer are driven by mutations to a protein called EGFR. Bauml, who treated lung cancer patients as a clinician for about 10 years, said EGFR-mutated lung cancer tends to develop in people who have little to no history of tobacco exposure. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers; EGFR-mutant cancer accounts for between 15% and 30% of those cancers. The higher end of that range is in Asia.
Targeted therapies are available that address EGFR. Tagrisso, AstraZeneca’s top cancer product accounting for about $6.6 billion in revenue last year, is one such drug. This oral small molecule is designed to block enzymes that drive cancer growth and it has become a standard therapy for patients with certain EGFR mutations. But one problem with these medicines is that when cancer mutates, it becomes resistant to the drug.
J&J’s Rybrevant is a bispecific antibody that offers two mechanisms of action. In addition to blocking EGFR, it blocks a second receptor called MET. Both receptors are overexpressed on the surface of cancer cells. If a cancer mutates around EGFR, Rybrevant’s activity on MET target still addresses the cancer. Blocking both targets is intended to prevent drug resistance. Rybrevant won accelerated FDA approval in 2021 as a second-line treatment for NSCLC driven by an exon 20 insertion mutation to EGFR. In March 2024, the FDA approved Rybrevant as a first-line treatment for such cancers, a decision that also converted the drug’s status to full approval.
Last August, the FDA approved another J&J drug, lazertinib (brand name Lazcluze), as a first-line treatment for EGFR-mutated NSCLC. Lazcluze also blocks EGFR, but as an oral small molecule, it passes through the cell membrane and binds to the target from the inside of the cell, Bauml said. This drug was approved for use alongside Rybrevant.
“They’ll prevent the resistance before it even happens,” Bauml said of the two drugs together. “If you mess with the binding of Rybrevant on top [of the cell], I’ve still got the inside. The whole idea is this dual approach allows for even more activity.”
There’s more to the way that Rybrevant works. The tail end of a bispecific antibody, called the Fc region, interacts with the immune system. Bauml said Rybrevant’s Fc region has been optimized to recruit immune cells. While it’s hard to show this effect in humans, in lab tests, exposure of tumors to the drug led to immune cell activity against them, Bauml said.
The J&J multiple myeloma portfolio spans antibodies (Darzalex), bispecific T cell engagers (Talvey and Tecvayli), and cell therapy (Carvykti). J&J is literally borrowing from multiple myeloma to grow its lung cancer pipeline. The company has explored Talvey and Tecvayli in lung cancer, Bauml said. Other types of drugs the company has studied for lung cancers include small molecules and radioligand therapies.
“Because of the expertise that we have at J&J, I don’t need to limit myself to any one modality,” Bauml said. “In fact, what I can do is say let’s find the best target and then we figure out the modality. Is it an ADC (antibody drug conjugate)? Is it a radioligand therapy? Is it a bispecific?”
J&J has projected $5 billion in peak revenue for Rybrevant. It has a long way to go. In the first quarter of 2025, Rybrevant and Lazcluze accounted for $141 million in revenue, up from $47 million in the same period in the prior year. It’s the first time the company has broken out specific financial figures for the therapy.
Growth for Rybrevant could come in different ways. As a bispecific antibody, the drug is administered as an infusion that takes between two to five hours. A subcutaneous version of the drug takes just five minutes, making it much easier for patients. At last year’s ASCO meeting, J&J reported Phase 3 results showing that subcutaneous Rybrevant was not only roughly comparable to the intravenous formulation, it actually led to improvement in overall survival. But last December, the FDA turned down this version of the drug citing issues with the manufacturing facility. No concerns were raised about the drug’s safety or efficacy, and Bauml noted that this injectable version of Rybrevant is already available in Europe. He added that the company is committed to bringing injectable Rybrevant to U.S. patients as soon as possible.
Additional growth for Rybrevant could come from outside of lung cancer. Bauml noted that EGFR and MET are associated with other malignancies. A Phase 1/2 study is evaluating Rybrevant in head and neck cancer. Bauml expects data will be presented at a future scientific meeting. Colorectal cancer is another opportunity. At the European Society for Medical Oncology annual meeting last year, J&J presented data from an open-label Phase 1b/2 study that evaluated Rybrevant, alongside standard chemotherapy, in 43 patients with metastatic colorectal cancer. Results showed the J&J drug led to a 49% overall response rate. Bauml noted that metastatic colorectal cancer generally cannot be cured. But in nine participants, the tumors got so small and showed such a good response to the therapy that patients were able to come off of the study because they were eligible for curative-intent surgery.
“So the impact of Rybrevant, it’s really just starting,” Bauml said. “We’re very excited about the data that we’ve demonstrated in [the] MARIPOSA [study with Lazcluze], but we believe that the best is yet to come.”
Photo: Mario Tama, Getty Images
