Biotech Values

[microcapfun]

HGSI/Albuferon

>>microcapfun et al re HGSI: Surprise! Monthly dosing of Albuferon is alive and kicking, but only for genotype-2/3 patients . The new phase-2b trial tests 900, 1200, and 1500mcg q4w doses; these are 50%, 67%, and 83%, respectively, of the 900mcg q2w dose that resulted in a successful phase-3 trial in this patient pool.<<

I still think the chance of success with q4w dosing is miniscule. The half life of Albuferon is ~150 hours, or 6.25 days. So the ratio of the trough concentration at 1500 mcg with q4w dosing to the trough concentration of 900 mcg with q2w dosing is

~(1500/900)*exp(-28/6.25)/exp(-14/6.25) = 0.18.

I.e. the trough concentration with the highest q4w dose being tested (which has peak concentration 25% higher than the q2w dose which caused too many severe pulmonary AEs!), is only 18% of the trough concentration of 900 mcg with q2w dosing - and the latter only *barely* passed the non-inferiority comparison to pegylated IFN.

Therefore 1500 mcg q4w has a good chance of failing on the basis of both safety and efficacy. If it fails on efficacy, obviously the lower q4w doses will fail worse.

micro