NH/Pyeongkuk Park
The author is an analyst for NH Investment & Securities. He can be reached at kyuha.lee@nhqv.com -- Ed.
Phase III MARIPOSA meets primary endpoint
Janssen announced positive topline results from the pivotal phase III MARIPOSA study evaluating Rybrevant (amivantamab) in combination with lazertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), versus Tagrisso as a first-line treatment in patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC). Global Therapeutic Area Head of Oncology at Janssen Research & Development and other experts note that EGFR-mutated NSCLC patients treated with third-generation TKI monotherapy have shown resistance, but promising data from MARIPOSA underscore the potential for the RYBREVANT + lazertinib regimen to advance treatment beyond TKI monotherapy and enter into frontline EGFR-mutated NSCLC as a future standard of care.
The MARIPOSA study met its primary endpoint with a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients receiving RYBREVANT plus lazertinib compared to Tagrisso. The combination of RYBREVANT and lazertinib demonstrated a safety profile consistent with previously reported data. A planned interim overall survival (OS) analysis showed a trend favoring the combination of RYBREVANT and lazertinib compared to Tagrisso. Patients in the study will be followed for subsequent OS analyses, which will determine statistical and clinical significance.
Five points deserve attention
1) Phase III MARIPOSA data comparison: In addition to combination methods, the MARIPOSA study also evaluates the efficacy of lazertinib alone in patients. The related data is expected to be disclosed at the upcoming ESMO. Yuhan conducted LASER301, a global phase III trial aiming to compare the efficacy of lazertinib versus first-gen gefitinib, and obtained approval in Korea as a first-line treatment. In EMs, including Korea, lazertinib’s rival drug is third-gen Tagrisso. Thus, it is worth paying attention to the Phase III MARIPOSA data regarding Leclaza and Tagrisso alone, as this will predict the drugs’ market shares in Asia, where EGFR mutation rates are high.
2) Timing of US launch: With the phase III MARIPOSA-2 (Tagrisso resistance) data and Phase III MARIPOSA data having met the primary endpoints, a request for approval is expected to be submitted immediately to the FDA. Considering that a standard review takes about ten months, the approval result should come out in 3Q24.
3) Yuhan’s capacity expansion: In our view, Yuhan is highly likely to produce lazertinib for Janssen, given: 1) Yuhan’s past production experience for Janssen’s lazertinib clinical trial; 2) the growing need for Janssen to outsource production to other regions; and 3) Yuhan’s capacity expansion completion, which is likely to arrive in line with Janssen’s obtaining of global approval for lazertinib. Even when applying conservative assumptions, Yuhan’s 2027F OP reaches W42.8bn (GPM of 15%), with expectations-beating margins. Yuhan kicked off a W90bn capacity expansion project in end-2022, aiming to complete the expansion by end-4Q23. Once completed, Yuhan’s capacity should expand to 840,000 liters.
4) Registration as a preferred treatment under NCCN guidelines: According to the latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), Tagrisso (osimertinib) is the only ‘preferred’ first-line therapy option in metastatic EGFRm (exon 19 deletion, exon 21 L858R mutation) NSCLC. That said, as the phase III MARIPOSA study has proven the superiority of the Rybrevant-lazertinib combo over Tagrisso, we are awaiting the listing in the NCCN Guidelines of the combo as a preferred therapy against metastatic EGFRm NSCLC.
5) AstraZeneca’s response with ADCs: Meanwhile, AstraZeneca has been responding to Janssen’s aggression with a similar regimen to that of the MARIPOSA study. At ASCO 2023 (held in June), AstraZeneca unveiled a phase I study design for AZD9592, an EGFR/c-MET targeted bispecific antibody drug conjugate (ADC). We believe that Janssen is paying close attention to AZD9592, as the substance overlaps with Rybrevant for being an EGFR/c-MET antibody applied with ADC technology. In particular, it should be noted that the importance of MET was well proven at the June ASCO meeting, with Merck’s study on Tagrisso resistance based on the FISH method revealing that MET amplification was detected in 50.6% of patients with Tagrisso resistance.