Camizestrant causes reversible pharmacological effects on retinal responses in rats

Some patients treated with camizestrant in the SERENA-1 and SERENA-2 clinical trials experienced mild, transient, reversible visual effects. This nonclinical investigation used electroretinograms (ERGs) and mass spectrometry imaging to examine the effect of camizestrant on retinal responses in rats and to investigate the origin of the visual effects observed in humans. Mass spectrometry imaging was used to confirm the presence of camizestrant in the retina of rats following 7 consecutive days of dosing (75 mg kg^-1/day). A separate group of rats then received doses of either camizestrant (5, 12, 25, or 75 mg kg^-1/day) or control over 7 consecutive days. They were observed for 7 additional days without further dosing. ERGs were conducted at baseline, Days 1 and 7, and 7 days after last dose to assess changes in retinal responses. Ophthalmic examinations were conducted pre-dose and on Days 8 and 15. Administration of camizestrant at ≥12 mg kg^-1/day significantly reduced dark-adapted ERG b-waves and oscillatory potential amplitudes, increased light-adapted b-wave amplitude and latency, and reduced the rate of light adaptation. All observed effects were dose dependent and reversible, returning to baseline levels a week after post-dose washout. There was no evidence of any structural changes in the eye. The results support a reversible, pharmacological effect of camizestrant on retinal responses in the absence of structural changes and are consistent with clinical findings. These data offer insight into the potential mechanism of the visual effects observed in patients.