Johnson & Johnson's Rybrevant Infusion-Related Reactions Significantly Reduced to 22.5% with Dexamethasone Pre-Administration in Phase 2 Trial
Clinical Trial to Improve the Convenience of Amivantamab Administration
Johnson & Johnson (JNJ)'s bispecific antibody, amivantamab (Rybrevant), in combination with lazertinib (Lazcluze), is gaining attention as an innovative first-line treatment for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, the high rate of infusion-related reactions (IRRs) associated with intravenous administration (67.4%) has been a significant limitation. The SKIPPirr Phase 2 trial (NCT05663866) was designed to address this by evaluating various pre-medication regimens to enhance patient safety and reduce treatment discontinuation rates. Mitigating adverse effects is not only crucial for the clinical value of the drug but also a key factor in its commercial success.
Efficacy of Dexamethasone 8mg Confirmed and IRRs Reduced
The clinical study individually evaluated the prophylactic effects of dexamethasone, montelukast, and methotrexate to identify the most effective combination. Among these, a protocol involving the oral administration of dexamethasone 8mg twice daily for two days before administration, with an additional dose on the morning of the infusion, demonstrated the best results. In the patient group receiving this regimen, the incidence of IRRs on the first day of administration was reduced from the historical control rate of 67.4% to 22.5%, a significant improvement. This regimen met the efficacy criteria in the trial design and is expected to establish a new standard for overcoming adverse effects, leading to an expanded cohort study.
Rybrevant's Survival Strategy Amidst Competition with Tagrisso
Currently, in the first-line treatment market for EGFR-mutated NSCLC, AstraZeneca's Tagrisso (osimertinib) holds a dominant position with annual prescription sales of $6 billion. Johnson & Johnson (JNJ) has faced challenges in market penetration with Rybrevant and Lazcluze, despite their high therapeutic efficacy, due to the inconvenience of managing adverse effects. The validated dexamethasone pre-medication regimen is expected to strengthen the convenience of intravenous administration, providing a strong foundation for expanding market share. Furthermore, it is expected to synergize with Rybrevant Faspro, the subcutaneous formulation approved by the U.S. Food and Drug Administration (FDA) in December 2025, to significantly improve physician prescribing preferences, creating substantial business value.
Synergy with Yuhan Corporation and Inflow of Global Technology Royalties
This clinical success is also considered a positive development for Yuhan Corporation (000100.KS), the original developer of lazertinib, as it provides a strong financial boost. In November 2018, Yuhan Corporation entered into a licensing agreement with Janssen Biotech to transfer global development and commercialization rights for a total of $1.25 billion. As of May 2026, it has already secured $300 million in milestone payments, and further milestone payments and high-double-digit royalty revenues are expected upon launch and expanded prescription. With the reduced barrier to prescription resulting from this clinical trial, Yuhan Corporation's pipeline value and cash flow are also expected to improve significantly in the long term.
The EGFR-mutated NSCLC treatment market is projected to grow from approximately $6.6 billion in 2025 to $14.2 billion in 2036, with AstraZeneca's Tagrisso establishing itself as a strong competitive standard of care. In the SKIPPirr Phase 2 trial, Johnson & Johnson (JNJ) demonstrated that pre-administration of dexamethasone 8mg reduced the incidence of infusion-related reactions (IRRs) associated with Rybrevant (amivantamab) from 67.4% to 22.5%. This will significantly improve patient safety and compliance, serving as a key factor in driving short-term prescription growth. In the medium to long term, it is expected to create a foundation for shifting market leadership by providing differentiated convenience compared to competitors through synergy with the subcutaneous formulation, Rybrevant Faspro. Additionally, it will accelerate the receipt of milestone payments and royalties under the $1.25 billion technology transfer agreement with its partner, Yuhan Corporation.
Source: ClinicalTrials.gov (api_ct)