HansGarrincha schreef op 11 november 2015 14:52:
$GLPG MorganStanley: 1st Take:
ABT-494 Safety Data Makes
Not Licensing Filgotinib Even More CuriousOn 11/10, the BALANCE I Study of ABT-494 was presented at ACR as a
late-breaking poster: ABT-494 is AbbVie's JAK inhibitor for the treatment of
Rheumatoid Arthritis (RA). BALANCE I is one of two PhII studies that AbbVie
ran with ABT-494. BALANCE I looks at ABT-494 in combination with
methotrexate in TNF failures or non-responders. Recall AbbVie choose to
develop ABT-494 instead of in-licensing Galapagos' filgotinib.
Today's data is
the first safety data we have seen from ABT-494, prior efficacy data was
disclosed in AbbVie's press release. A full copy of the BALANCE I poster is
available here:
www.abbviescience.com/11151318/14.Efficacy in line with prior disclosures: Versus placebo there appears to be a
dose effect up to 6mg, but after 6mg, there appears to be a plateau of
response. That said, the slope of response is higher with higher doses (i.e.,
higher doses reach maximal effect sooner). The impact of 1 or >2 prior TNF
drugs does not appear to have a significant impact on efficacy with ACR20
scores ~20% above placebo irrespective or prior TNF use.
Safety appears to suggest ABT-494 is JAK1 selective, but not JAK1
specific and in our view favors filgotinib: On the key safety data -
hemoglobin (Hb), ALT/AST, neutrophils, lymphocytes and NK cells - all appear
to head the wrong direction on ABT-494. Specifically, Hb has a downward
slope with the highest dose seeing mean Hb declines of ~1g/dL. This
compares with Hb changes of 0 to +0.4 g/dL with filgotinib in DARWIN1.
While there are modest changes with neutrophils and lymphocytes, NK cells
decline significantly (p<0.001 for all doses vs placebo) for ABT-494. This
compares with no change from baseline in NK cells for filgotinib in DARWIN1.
Finally, Gr2 ALT/AST increases appeared dose dependant with ABT-494
with the highest dose seeing 11% and 7%, resp., of patients at 2.5-5x ULN.
This
compares to no Gr2 or worse ALT/AST increases for filgotinib in DARWIN2
(ALT/AST was not presented in DARWIN1).case for solid new licensing deal for filgotinib: This data increases our
confidence that filgotinib is positioned well as Galapagos engages in talks to
repartner following AbbVie's return of the molecule. See our recent note from
our dinner with mgt. for more details.