Abbvie to Galapagos: "It's not you, it's me"

Abbvie has decided to pass up the chance to co-develop filgotinib, preferring to advance their own internal candidate ABT-494 into phase 3 trials in rheumatoid arthritis. Admittedly, this came as an initial surprise given the strong efficacy results posted by filgotinib in the DARWIN1 and 2 trials. However, Abbvie has provided 12 week data for ABT-494, allowing a quick comparison of the 12 week data across oral JAK inhibitors in rheumatoid arthritis:

ACR70 Data Across Trials (12 week time point)

Tofacinitib data from 2x5 mg arm of Study IV, 2 mg arms of RA-BUILD and RA-BEACON, 2x100 mg arm of DARWIN1, 100 mg arm of DARWIN2 and 6 mg twice-daily arms of Balances -I and II. Data are a mix of LOCF and NRI reporting.

Given these data, Abbvie’s decision is not surprising. The spread in efficacy across the various JAK inhibitors suggests ABT-494 will be very competitive, and has the added benefit of being internally developed and wholly owned. Abbie also reports that they will be moving ABT-494 into phase 3 by the end of the year, serving their intent to rapidly capitalize on the phase 2 Balance data. This left Galapagos to announce that they’re already courting offers, but that phase 3 studies will begin no sooner than early 2016. Of these three investigational JAK inhibitors, this leaves baricitinib closest to an NDA, followed by ABT-494 and then filgotinib.

Since filgotinib’s future is the most speculative of the three, some general points bear consideration in predicting the type of deal Galapagos can expect to garner in a subsequent partnership. A data package including DARWIN1 and 2 would often be considered a de-risking proposition by potential suitors, allowing Galapagos to command more favourable deal terms. However, the following points may suggest that a future deal for filgotinib may not be as lucrative, or may result in Galapagos assuming more of the financial and regulatory risk than previously:

- Filgotinib will potentially be the 4th JAK inhibitor on the market after tofacitinib, baricitinib and ABT-494. With Abbvie rapidly moving into phase 3 trials, they seem to have done their best to ensure that Galapagos is a step behind. Any potential suitor will have to consider this as a major negative to the economics of the collaboration.

- Galapagos has claimed filgotinib is the most JAK1 selective (over JAK2) of the investigational inhibitors, potentially conferring a safety advantage over predecessors like tofacitinib and baricitinib. This was often underlined by a focus on the anemia side effect profile, a talking point that I suggested was largely overblown. Galapagos claims that filgotinib is 3x more JAK1 selective than ABT-494 and by their own internal data, they claim filgotinib is also 3x more JAK1 selective than tofacitinib. This would place ABT-494 around the same JAK1 selectivity range as tofacitinib. In effect, Abbvie does not appear to be daunted by the proposition that JAK1 selectivity is a de facto advantage. In that regard, this selling point may not resonate as well with potential suitors.

- The FDA and Galapagos agreed to exclude men from the 200 mg daily dose group, centered around a potential concern for side effects to the male fertility system. Even though the daily 100 mg dose groups look strong from an efficacy perspective, the potential suitor may deem that this issue merits consideration and, subsequently, a commitment of time and resources to address.

In sum, I remain of the opinion that filgotinib is an efficacious drug for rheumatoid arthritis and Galapagos will be able to find another collaborator. However, I suspect the new deal will not be as favourable as the previous.



Postscript / Erratum:

A previous version of this entry suggested Eli Lilly and Abbvie had comparable legacies in RA disease modifying agents. That can safely be considered as incorrect and has been edited. Hat tip.