Regeneron could reap big rewards from high-dose Eylea

 Regeneron’s 19% stock surge yesterday added $12bn to its market cap, taking its valuation higher than that of the pharma giant GSK; investors were clearly impressed with data on high-dose Eylea. Two crucial pivotal trials succeeded in showing that the project, given at four-monthly intervals, worked as well as the original formulation, dosed every two months. Long-acting Eylea is a vital component of Regeneron’s defence against biosimilars, which could start in the US in 2024. And because the high-dose product will probably be filed under a new BLA it might be exempt from Medicare price negotiations. Analysts reckon the high-dose product could also help fend off a new rival, Roche’s bispecific Vabysmo, which is also available at long dosing intervals. SVB Securities pointed out that 77% of wet AMD patients managed to stay on high-dose Eylea dosed every four months, versus 45% for Vabysmo on this schedule. Echoing upgrades from across the sellside the bank substantially hiked future Eylea forecasts, adding a huge 30% to their 2030 estimate, to $17bn. Still, Roche recently presented two-year data showing that 45% had improved to 60% at two years, so the Vabysmo threat is far from neutralised.

Eylea vs Vabysmo in wet AMD
	Pulsar (NCT04423718)			Tenaya (NCT03823287)		Lucerne (NCT03823300)
Drug	Eylea (control)	Eylea 8mg	Eylea 8mg	Eylea 2mg (control)	Vabysmo	Eylea 2mg (control)	Vabysmo
Regimen	Q8wk	Q12wk	Q16wk	Q8wk	Variable	Q8wk	Variable
N	336	335	338	337	334	337	331
Mean observed BCVA improvement (letters)	7.6	6.7	6.2	6.6	5.8	5.1	6.6
LS mean difference in BCVA improvement (primary endpoint)		-0.97	-1.14		0.7		0.0
Non-inferiority p-value*		0.0009	0.0011
Patients maintained on dosing interval, without need for regimen modification		79%	77%		45%**		45%**
*Non-inferiority (1-sided) p-values are for the difference in least squares mean compared to Eylea with margin of 4 letters. **16wk regimen. BCVA=best corrected visual acuity; LS=least square.

 

Eylea vs Vabysmo in diabetic macular oedema
	Photon (NCT04429503)			Yosemite (NCT03622580)			Rhine (NCT03622593)
Drug	Eylea (control)	Eylea 8mg	Eylea 8mg	Eylea (control)	Vaby-smo	Vabysmo	Eylea (control)	Vaby-smo	Vabysmo
Regimen	Q8wk	Q12wk	Q16wk	Q8wk	Q8wk	Variable	Q8wk	Q8wk	Variable
N	167	328	163	312	315	313	315	317	319
Mean observed BCVA improvement (letters)	9.2	8.8	7.9	10.9	10.7	11.6	10.3	11.8	10.8
LS mean difference in BCVA improvement (primary endpoint)		-0.6	-1.4		-0.2	0.7		1.5	0.5
Non-inferiority p-value*		<0.0001	0.0031
Patients maintained on dosing interval, without need for regimen modification		91%	89%
*Non-inferiority (1-sided) p-values are for the difference in least squares mean compared to Eylea with margin of 4 letters. Yosemite and Rhine data are averages of weeks 48, 52 and 56. BCVA=best corrected visual acuity; LS=least square. https://www.evaluate.com/vantage/articles/news/trial-results-snippets/regeneron-could-reap-big-rewards-high-dose-eylea