ASCO: J&J's Injectable Rybrevant Outperforms Intravenous Version in Extending Lung Cancer Patients' Lives

Johnson & Johnson has achieved an unexpected success with a new subcutaneous (SC) formulation of its lung cancer medication, Rybrevant, which outperformed the original intravenous (IV) version. This development could position Johnson & Johnson as a strong competitor against AstraZeneca’s prominent lung cancer treatment, Tagrisso.

Typically, the goal in developing an injectable version of an IV drug is to offer more convenience without compromising efficacy. However, the SC formulation of Rybrevant surpassed expectations by significantly reducing the risk of death by 38% compared to its IV counterpart. This finding emerged from a study involving non-small cell lung cancer (NSCLC) patients who had been previously treated and had common EGFR mutations, specifically ex19del or L858R.

One year after treatment, 65% of patients receiving the SC version of Rybrevant in combination with lazertinib were still alive, compared to 51% of those who received the IV version with lazertinib. These promising results were shared at the American Society of Clinical Oncology annual meeting in Chicago, where the PALOMA-3 trial data was presented. Though overall survival was only an exploratory endpoint in the trial, the results were statistically significant with a p-value of 0.017, and the confidence interval was below 1.

In addition to improving overall survival, the SC version of Rybrevant also demonstrated longer durations of response and progression-free survival compared to the IV formulation. The tumor response rates were similar between the two formulations, at 30% for SC and 33% for IV.

Concerning the trial's co-primary endpoints, the SC formulation showed noninferior pharmacokinetic efficacy, which was assessed based on drug levels in the blood before the next dose and the average levels over a 15-day period. Safety and tolerability were also better with the SC version, as the rate of infusion-related reactions was significantly lower (13% for SC versus 66% for IV). Although some adverse effects like paronychia, hypoalbuminemia, and rash were slightly higher with the SC formulation, none were severe (grades 4 or 5).

The reduced administration time of the SC version, which takes only five to seven minutes compared to up to five hours for the IV version, adds another layer of convenience and appeal. Johnson & Johnson plans to submit the SC formulation to the FDA within the year. This submission is independent of the awaited FDA decision regarding the combination of IV Rybrevant and lazertinib for first-line EGFR-mutated NSCLC.

Achieving a significant survival benefit in SC-versus-IV studies is rare, as these trials typically aim to demonstrate pharmacokinetic noninferiority. Nevertheless, Johnson & Johnson intends to continue offering the IV version of Rybrevant despite the SC formulation's superior performance.

Researchers believe that the enhanced efficacy of the SC formulation may be due to its absorption through the lymphatic system, which could boost immune-mediated activity. Rybrevant, being an EGFR-MET bispecific antibody, has shown capabilities in directing immune cell activity, employing monocytes, macrophages, and NK cells to target and kill cancer cells.

This advancement provides hope for better treatment options for lung cancer patients and could strengthen Johnson & Johnson's market position, potentially challenging the dominance of AstraZeneca’s Tagrisso.