BIOTECH · @_B_I_O_T_E_C_H_
9th Sep 2016 from TwitLonger
$ACHN Jeff: HCV Regimen Active, But Unknowns Remain
About Its Future Competitiveness
Data from #EASL16 Special Conference abstracts for ACHN/JNJ’s HCV combos
were just made available and show potential activity of their triple combo
in treatment-naive GT-1 HCV patients. However, with data not yet complete
and dosing/safety still being optimized, risks remain, and potentially
differentiating advantages from existing or later-stage treatments -- which
would enable future market competitiveness -- are still unclear.
High SVR observed with 8wk triple regimen. For patients on the PI/NS5A/nuc
combo, SVR rates were 100% (40/40). While GILD already achieves very high SVRs over
8 weeks with their tried-and-true dual regimen, Harvoni, it is possible that ACHN/JNJ
may be accomplishing in both low and high viral load patients (baseline characteristics
expected at meeting). More data, including in sicker patients, will be important to know how
consistently ACHN/JNJ’s triple can produce high SVRs at 8 weeks and how it might compare
to GILD’s own 8-week triple, sof/vel/vox, which is further along and is completing ph.III.
Dual-combo off the table; near-term data should elucidate potential for 6-week
dosing with triple. Based on two viral rebounds observed in the 8 week dual NS5A
arm, we have confirmed that ACHN/JNJ will no longer pursue a dual-regimen -- slightly
disappointing, given results of the pilot “proxy” odalasvir-sofosbuvir study, which had
shown 100% SVRs with an odalasvir containing dual-regimen with both 8- and even 6-week
treatment durations, and could have been a differentiating feature. (We speculate this may
be due to either AL-335 being less potent than sofosbuvir, or to odalasvir dosing/exposure
still being optimized). The 6 week triple-regimen showed promising 100% EoT suppression,
and given JNJ’s plan to explore a 6 week regimen in ph.IIb, we believe SVR data available
at the meeting in 2 weeks could look promising and indicate a potential future path for the
cocktail.
Safety signal warranted further dose optimization; bar is high, given clean
safety in existing therapies. The abstract reported one patient developed a serious AE,
asymptomatic second degree AV block seen on ECG; our understanding is that this was
attributed to ACHN’s odalasvir component, given the super-therapeutic exposure levels
observed in the first cohort and what we have learned to have been one prior similar signal
seen in previous studies at super-therapeutic doses. While there still looks to be a reasonable
therapeutic window for odalasvir given the totality of the data from this and other studies
with optimized doses/exposures (high exposures initially seen here were due to a DDI),
and the program continues presumably with regulatory sign-off, longer-term we expect
regulators and clinicians will have a very high safety bar given the safety/experience of
existing HCV treatments.