Galapagos finds little comfort in safety

Filgotinib’s mixed efficacy in ulcerative colitis prompts a shares slide.

Trial Results

Is filgotinib one of the safest Jak inhibitors for ulcerative colitis? Probably, according to the results from the Selection trial released late yesterday. Is it one of the most effective? Not so much, an opinion confirmed by the 6% share price slide in Galapagos stock this morning.

With other Jak inhibitors with efficacy comparable to filgotinib's already on the market for UC, as well as Abbvie’s Rivoq with its much higher efficacy, and the lower 100mg dose of filgotinib failing to hit its primary endpoint, this now leaves Galapagos needing to persuade regulators that filgotinib's reputation as the cleanest in the class is worth reflecting on a prescribing label.

No bragging rights here

The phase IIb/III study enrolled 1,348 adults with moderate to severe UC who had either previously taken a biological or were biological-naive. These were initially randomised to either placebo, 200mg of filgotinib once daily or 100mg once daily, for 10 weeks. The primary endpoint for this induction phase was placebo-compared remission, and responders were then re-randomised to 48-week maintenance.

It was filgotinib’s performance in the induction phase that appears to have caused the stock price movement. The 100mg dose failed to beat placebo, while the 200mg dose did hit – but even the performance of this higher dose was not the slam-dunk investors had been hoping for.

At week 10 biological-naive subjects on the 200mg dose achieved a 10.8% placebo-adjusted remission rate, while biological-experienced patients achieved a 7.3% rate. So at best filgotinib can boast similar efficacy to Xeljanz, caveats about cross-trial comparisons withstanding; at worst, filgotinib significantly lags Abbvie’s Rinvoq on the efficacy front (Three out of four is not bad for Abbvie’s Jak, October 23, 2018).

With hindsight

Before the results were released Galapagos’s management had tempted fate by saying they were expecting filgotinib to fall somewhere near the placebo-adjusted remission rates for Rinvoq.

Ulcerative colitis efficacy comparison (placebo-adjusted)
Galapagos/Gilead, filgotinib Abbvie, Rinvoq
200mg biological-naive – 10.8% 45mg – 20%
200mg biological-experienced – 7.3% 30mg – 14%
100mg – not statistically significant 15mg – 14%

The miss on this measure will only compound concerns about filgotinib’s commercial potential in UC, so even more will be riding on filgotinib’s much-lauded safety profile cutting a lot of ice with the regulators. In the Selection trial the project's clean track record held up, with similar bleeding, herpes zoster infection and GI issues across all arms.  

The big question will be whether this is enough to help it avoid the black box warning other Jaks have been slapped with. Many are expecting Gilead, Galapagos’s partner, to file in the US in the second half of the year. However, the important Manta and Manta-ray studies, examining tescticular toxicity, have been halted because of Covid-19, and it is unclear if the regulator will accept a filing without these safety data.  

The two studies are pertinent in UC because unlike arthritis this disease tends to affect younger patients who will have to take the drug for longer.

Acing the Manta studies would add more valuable safety data, which some have speculated could see the product used in earlier lines of disease, giving it a competitive edge over the likes of Xeljanz and potentially boosting sales. The drug is forecast to generate revenues of $1.86bn in 2026, according to sellside consensus figures from EvaluatePharma.

Filgotinib might have lost the efficacy battle, but increasing UC sales could still be in its grasp.

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