PhIIb miss muddies waters ahead of AbbVie opt-in decision on RA drug

(By Bernd Brägelmann Braegel Mit freundlicher Genehmigung von Dr. Martin Steinhoff - Own work, CC BY 3.0,

Ablynx has posted data from the second Phase IIb trial of its anti-IL-6R rheumatoid arthritis drug, triggering the start of a countdown to AbbVie’s ($ABBV) opt-in decision. But, with a strong placebo response resulting in all bar one cohort missing the primary endpoint, it is as unclear as ever whether AbbVie will pay the $75 million it needs to license the program.

The trial gave vobarilizumab, a drug based on a single-domain antibody fragment, to 354 patients with moderate to severe rheumatoid arthritis who were already taking methotrexate. Participants received either one of four regimens of vobarilizumab, covering different doses given subcutaneously every two or four weeks, or a placebo. Changes in the ACR scores of subjects were assessed after 12 and 24 weeks.

In isolation, the data from the vobarilizumab arms look solid, while perhaps falling short of the levels needed to guarantee a positive opt-in decision by AbbVie. Depending on the dosing schedule, between 72% and 81% of participants experienced a 20% improvement in their symptoms after 12 weeks. In comparison, 75% of subjects achieved the same improvement when given GlaxoSmithKline ($GSK) and Johnson & Johnson’s ($JNJ) IL-6 drug sirukumab plus methotrexate in a Phase II trial.

While inter-trial comparisons can be unreliable, those data suggest vobarilizumab’s efficacy should be competitive. Data on ACR50 and ACR70, which, respectively, show whether a patient’s symptoms have improved by 50% or 70%, also look solid across multiple different regimens and after 12 and 24 weeks of treatment. However, in a highly competitive environment, ”solid” might not be enough to persuade AbbVie to open its wallet.

The case in favor of vobarilizumab was undermined further by the performance of the placebo arm. After 12 weeks, 62% of patients in the placebo arm achieved ACR20. This is just short of the numbers seen in the vobarilizumab arm and led to the trial missing its primary endpoint. Against ACR50 after 12 weeks, the placebo arm came within one percentage point of matching the performance of the lowest, most infrequent dosing of vobarilizumab. The cause of the high placebo response is unclear.

AbbVie must now assess whether vobarilizumab is worth any more of its time and money. Ablynx gave AbbVie an option on the drug as part of a deal that netted it $175 million upfront in 2013. Since then, J&J and GSK and Regeneron ($REGN) and Sanofi ($SNY) have hustled their anti-IL-6 antibodies to the cusp of regulatory approvals, leaving vobarilizumab with the prospect of coming to market long after its rivals with comparable efficacy data.

The composition of AbbVie’s rheumatoid arthritis pipeline has also evolved since it struck the initial Ablynx deal. In its search for drugs that can cannibalize its Humira franchise before competitors do so, AbbVie is working on a raft of late-phase trials of in-house prospect ABT-494.

Ablynx stock rose 7% in early trading in Brussels.

- read the release

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