AbbVie Knocks Back Ablynx's Vobarilizumab In RA

Ablynx NV plans to initiate end of Phase II meetings with US and European regulators shortly with a view to beginning a Phase III study by the end of next year following AbbVie Inc.'s decision not to opt in to a license for vobarilizumab in rheumatoid arthritis.

"We were always confident that if AbbVie made an entirely data driven decision, then it would go ahead [and opt in]," Ablynx CEO Edwin Moses told Scrip. "The product has looked good against everything it has been tested against."

Edwin Moses

Ablynx

But he noted that in a recent R&D event, AbbVie had "around 150 slides detailing its oncology portfolio, and just 25 in immunology”. So despite only being given formal notice "last night", AbbVie's decision has not come as a complete surprise. "The move clearly comes on the back of a significant corporate shift towards oncology that we could not have envisaged three years ago when we entered the collaboration."

Ablynx had built what it thought was a solid case for AbbVie to take on vobarilizumab as a potential successor to its anti-TNF biologic Humira (adalimumab).

Vobarilizumab is an anti-IL6 receptor nanobody, and would compete with Roche's IL-6 inhibitor Actemra (tocilizumab). In addition, GlaxoSmithKline PLC and Regeneron Pharmaceuticals Inc./Sanofi have late-stage anti-IL-6 biologics that could garner approval in 2017.

Jefferies analysts commented: "Given the highly competitive landscape of biologics targeting IL-6, in addition to the already crowded market of approved drugs and novel small molecules in clinical development for RA, we have conservative forecasts for the commercial potential of vobarilizumab."

However, Moses believes vobarilizumab can compete with Actemra and the two late-stage candidates on the basis of safety and efficacy. "What we have is a considerable step ahead of all three," he stated.

In a head-to-head study of vobarilizumab against Actemra, "50% more patients achieved remission," he said. Vobarilizumab also has a more convenient dosing schedule, he noted. (Also see "Ablynx Builds Case For AbbVie Option On Humira Successor" - Scrip, 7 Jul, 2016.)

There had been confusion over a high placebo response in an earlier Phase II study but Moses explained that further analysis revealed that the highest placebo responses were in countries with limited access to biologics, suggesting trial design and geographical factors accounted for the effect.

Ablynx will start looking for a new licensing partner but Moses stressed that development of vobarilizumab will not stall during the search. "We are in a position where we can start Phase III development without having a partner on board." The company is financed through 2017 and according to the CEO, into the second half of 2018.

Jefferies analysts believe AbbVie's decision was "hard to call" because while Phase IIb data were encouraging in both reported trials, it remained unclear whether vobarilizumab would be a "must-have product for AbbVie to underpin/replace its leading Humira franchise". They noted that AbbVie still has rights to opt-in to development for SLE following Phase II data in 2018. "It is possible that AbbVie would prefer to concentrate on its oral JAK inhibitor, ABT-494, which is currently in Phase III development," they added.

Consolation

Ablynx, which loses out on a $75m milestone payment, will be consoling itself by the outcome of Galapagos' rejection by AbbVie in RA last year.

Galapagos NV had its own option agreement with AbbVie for the JAK 1 inhibitor filgotinib, and got a major shock in 2015 when AbbVie decided not to pursue the product despite excellent Phase II data.

However, Galapagos bounced back and secured a new deal within months with Gilead Sciences Inc. which included $725m up front.