October 20th, 2016
By: Simon King
Tags: ViewPoints ABT-494 filgotinib sarilumab sirukumab vobarilizumab AbbVie Ablynx Galapagos Gilead GSK Sanofi Arthritis General Practice Internal Medicine Clinical Research (R&D) Licensing
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AbbVie has confirmed it will not opt-in to Phase III development of vobarilizumab for the treatment of rheumatoid arthritis (RA), putting the onus is on Ablynx to find another late-stage partner.
Encouragingly for the Belgian biotech, key opinion leaders (KOLs) remain optimistic about the clinical profile for vobarilizumab, which is an anti-IL-6R antibody.
However, AbbVie's decision is not that surprising; Phase IIb data suggests minimal differentiation for vobarilizumab versus same class agents, while rheumatologists appear unconvinced that additional anti-IL6 antibodies will offer anything new to the treatment paradigm for RA (Physician Views Poll Results: Feedback from 50-plus rheumatologists indicates niche usage beckons for sirukumab and sarilumab in RA).
Phase IIb data for vobarilizumab in moderate-to-severe RA patients was released in August and touted by Ablynx as "compelling."
A counterview – now confirmed in the eyes of AbbVie management – is that vobarilizumab is not sufficiently differentiated from well-established RA therapies, which are already on the market, or other biologics targeting IL-6, which are in mid-to-late stage development; as Jefferies analyst Peter Welford had previously suggested, would AbbVie perceive vobarilizumab as a "must have" product (ViewPoints: Ablynx data leave AbbVie with plenty to think about before deciding on vobarilizumab opt-in).
With the Big Pharma company having decided that vobarilizumab will not be part of its strategy to defend share of the RA market as Humira revenues come under biosimilar threat, Ablynx will seek a new development partner with a view to initiating Phase III development by the end of 2017.
It will be hoping to replicate the success of cross-town rival Galapagos, which also lost AbbVie as a late-stage development partner last year, for the oral JAK inhibitor filgotinib in RA, but quickly found a willing replacement in Gilead Sciences and secured a lucrative deal to boot. As Welford notes, these two decisions by AbbVie are likely entwined; the company may be prioritising development of its own JAK inhibitor ABT-494 over both filgotinib and vobarilizumab.
A high placebo-response in mid-stage testing somewhat confounded analysis of the vobarilizumab data, but KOLs recently interviewed by FirstWord's Therapy Trends team are unconcerned about this, noting that high expectation rates among the significant proportion of patients enrolled from South American countries will have had a pronounced effect on placebo response.
In the Phase IIb study, a 20 percent improvement in ACR20 scores was seen in up to 81 percent of vobarilizumab-treated patients at week 12. From week 12 to week 24, vobarilizumab induced continued improvement in higher level responses with ACR50 and ACR70 scores of up to 59 percent and 43 percent at week 24, respectively. Moreover, the results demonstrated that vobarilizumab had a rapid and strong impact on disease activity with up to 49 percent of vobarilizumab-treated patients achieving clinical remission at week 24 compared to 17 percent of patients receiving placebo.
Based on these data, some KOLs remain confident that vobarilizumab will likely be a strong competitor to other IL-6/IL-6R agonists, potentially also because of its novel mechanism of action, although others are more cautious, partially as they expect ACR improvement rates to be lower in Phase III than Phase II trials.
One expert noted "the data are quite remarkable, and I cannot see why this drug shouldn't be effective because to my knowledge it is also directed against the receptor. So it should act like Actemra or sarilumab. One advantage is that they're quite small and so they might penetrate the tissue sites better than the large molecules. This is always a speculation, that's why they started with these nanobodies, also they're a little bit easier to produce because they're smaller."
However, another KOL counters that "if the Phase III trial shows that it has a clear dose dependency and has clinical efficacy in the range of what is expected with anti-IL-6, then physicians will not make a difference whether it's a nanobody, or a receptor construct, an antibody against the receptor. It will position itself as a direct competitor to whatever other anti-IL-6 is on the market then."
By the time vobarilizumab reaches the market, GlaxoSmithKline and Johnson & Johnson's sirukumab and Sanofi and Regeneron's sarilumab are likely to be launched – with both products IL-6 targeting antibodies. Furthermore, of 59 rheumatologists recently polled by FirstWord, 37 percent described the unmet need for these agents as 'minimal', illustrating how crowded the biologics RA market is.
AbbVie, a market-leader in RA, has not seen enough to whet the appetite. The pressure is now on Ablynx to convince others that vobarilizumab can stand out from the crowd; with RA studies requiring enrolment of large patient numbers, Ablynx's cash position requires a partner sooner rather than later.