Van beursig:
Assuring voba results
Bron : KBC securities Michaël Vlemmix
News:
Ablynx released their long-anticipated topline phase 2b results of the
combination trial (incl. methotrexate) with the anti-IL-6R nanobody
vobarilizumab (voba) for the treatment of RA. The study already reached its
primary endpoint at week 12 based on ACR20 and voba recently reported
positive monotherapy results at week 12 (early July). Key items of the combo
trial: ACR20, ACR50 and ACR70 scores of up to 79%, 59% and 43% at week
24. Up to 49% of the patients in clinical remission at week 24 and excellent
safety profile at all doses. Monthly dosing shows potential and absolute
numbers show clear advantages vs. other anti-IL-6/IL-6R drugs.
Our view:
Overall results were best with bi-weekly dosing of 225mg with ACR20 of 74%
(plac: 74%), ACR50 of 59% (plac: 39%, p<0.05) and ACR70 43% (plac: 17%,
p<0.01), HAQ score of 65% (plac: 71%), DAS28crp remission of 49% (plac:
17%, p<0.001) and DAS28crp low disease activity or remission of 68% (plac:
29%, p<0.001) all at week 24 on top of methotrexate. Note immediately that
the placebo results for ACR20 are surprisingly high (62% w12, 74% w24).
Obtaining statistical significance is therefore not possible and could be an
artefact due to study design (discontinuation points based on ACR20 due to
no rescue treatment and post-study 2 year continuation on active drug).
Safety: Excellent safety profile through week 24. TRAE that led to study drug
discontinuation was 6.5% for voba compared to 4.3% for placebo. TRSAE was
1.8% for voba vs. 2.9% placebo without dose dependency. Abnormal liver
function and neutrophil counts were infrequent across the study. No grade 3
decreases in absolute platelet counts were observed and voba showed no
effect on the mean LDL/HDL cholesterol ratio across all doses tested.
Conclusion:
As always, biotech isn’t black or white. The high placebo number of ACR20
causes no significance for voba in that parameter but we see several
convincing aspects in these results. First, clear significant results were
obtained in terms of ACR50, ACR70 and DAS28 remission/low disease activity
or remission with the bi-weekly dosing of 225mg voba. ACR50 level at 24
weekqs of that dosing regime is also currently one of the highest rates seen
across trials of competitors and in our opinion, DAS remission score is of higher
relevance than ACRs since they are more objective. When disregarding the
placebo results, de absolute numbers of voba are simply stated high. Second,
based on the DAS scores, 4-weekly administration of 150mg voba was proven
to be significant vs. placebo with beneficial ACR ratios (though not significant)
creating the potential for a monthly treatment (or induction with highest dose,
followed by monthly administration). Thirdly, general safety profile is excellent
creating a positive advantage vs. competitive IL-6R inhibitors. Further phase
III development is warranted and topline data has been sent to AbbVie. A
conference call is planned in the afternoon at 4pm CET for further details.