After witnessing the withering of its clinical-stage pipeline last year Galapagos will be hoping for an entirely different outcome from its next big test: an oral RA candidate which has been cornered by AbbVie.
Data are due to emerge over the next few months from a phase IIb programme testing the Jak-1 inhibitor, GLPG0634, and should it all look good the US pharma giant has an option to trigger a full-blown global deal. Shares in the Belgian company have almost doubled in value over the last few months, suggesting investors are confident in the outcome. But fierce competition in this disease area, including from elsewhere within AbbVie’s pipeline, means this is far from a foregone conclusion.
The first set of data likely to emerge are 12 week results from a study called Darwin 1, a 599-patient trial testing GLPG0634 as an add-on to methotrexate. The primary endpoint is the percentage of subjects achieving an ACR20 response at week 12 – a widely used measure of symptom improvement – although the trial will track patients for 24 weeks in total. Six different dosage schedules are being tested against placebo.
Darwin 2 is a monotherapy trial testing ‘0634 in 287 patients who have not responded to methotrexate; it uses the same primary endpoint and also tests various dose schedules. A third, 180-patient study is trialling the drug in Crohn’s disease; according to clinicaltrials.gov this is still recruiting patients.
Top-line readouts from the Darwin studies will start to emerge around the end of the first quarter, Galapagos said in November. A full 24-week data package should be delivered to AbbVie in the third quarter, upon which it will make its decision.
Best-in-class?
Galapagos boasts that ‘0634 demonstrated a best-in-class profile in phase IIa. Two four-week studies demonstrated clinical responses at a range of doses, while no cases of anaemia or changes in LDL and liver enzymes were detected – known side effects of this class.
For AbbVie to elect to push on, the molecule will have to prove this promise as well as stand up to other Jaks in the pipeline. The most notable competitor is Eli Lilly’s baricitinib, which has started generating top-line results from a large pivotal programme.
Detailed baracitinib data are anticipated at a medical conference, probably ACR in November in the US, and will be closely watched as they will likely set the new bar for other Jak contenders to beat.
‘0634 is probably closest behind baricitinib. But AbbVie is also doing fairly extensive mid-stage work on its in-house Jak inhibitor ABT-494 – around 500 patients are being recruited into two studies that should yield results later in the year.
The relative side effect profiles of these contenders will be crucial; these concerns have largely prevented first-to-market Xeljanz from living up to huge commercial expectations, so if baricitinib or ‘0634 can prove themselves at the very least safer alternatives, Lilly and AbbVie could still achieve what Pfizer failed to deliver for this class (Therapeutic focus – Jaks still need to prove worth in rheumatoid arthritis, December 12, 2014).
It is because the oral opportunity in RA remains wide open that this mechanism is still being pursued so enthusiastically, despite poor precedent. But Galapagos still needs to show that '0634 has a chance to be a leader of this market.
Make or break?
Early last year, Galapagos threw everything behind its drug development prowess when it sold a profitable service business to focus on its pipeline. Then partners GlaxoSmithKline and Johnson & Johnson scrapped work on two in-licensed clinical-stage candidates, while a third in-house project is struggling.
These setbacks leave investors focusing solely on ‘0634 and a phase I cystic fibrosis programme that is also partnered with AbbVie.
With shares at €19.65 and a market value of €597m, close to a record high, the market is keeping the faith for now. However AbbVie really needs to sign on the dotted line with '0634 for Galapagos to complete its evolution.
Darwin 1 NCT01888874
Darwin 2 NCT01894516
Crohn's disease NCT02048618
ABT-494 NCT02066389
To contact the writer of this story email Amy Brown in London at AmyB@epvantage.com or follow @AmyEPVantage on Twitter.
EvaluatePharma Ltd
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