Gilead's filgotinib fails midphase tests in lupus, Sjogren's

A clutch of Gilead drugs including filgotinib have failed to move the needle in midphase clinical trials of cutaneous lupus and Sjogren's syndrome patients. Neither trial hit the primary endpoint, although Gilead did see “evidence of activity” in patients taking filgotinib.

Gilead kicked off both studies in 2017 and primed investors to expect updates in the second half of 2019. The update arrived on Gilead’s third quarter results conference call when, prompted by an analyst question, SVP John Sundy revealed neither trial met its primary endpoint. Despite that blow, Gilead is yet to kill off hopes of developing filgotinib in the indications.

“We did see evidence of activity with filgotinib, particularly in patients who had markers or evidence of more active disease. So, we just got the first look at these data, we're looking at the full set of data from all of these studies and we'll determine the next steps that we take in lupus and Sjogren's disease,” Sundy said.

Both trials also tested lanraplenib, a Syk kinase inhibitor formerly known as GS-9876. The Sjogren's clinical trial also tested tirabrutinib, a BTK inhibitor Gilead is developing with Ono Pharmaceutical. Tirabrutinib used to be known as GS-4059.

Success in either indication could have opened up an untapped market for Gilead. Other companies including Biogen and Novartis are developing candidates against the diseases but patients are poorly served by the currently available treatment options.

The failures of the two clinical trials dampen hopes that Gilead’s assets will address those unmet needs but other avenues of R&D remain open to the drugs. Filgotinib, a Galapagos-partnered JAK1 inhibitor, is in late-phase development in several inflammatory conditions.

Gilead disclosed details of the failures on the same call as it revealed a shift in its HIV strategy, again when prompted by an analyst question. Gilead was advancing the nucleotide reverse transcriptase inhibitor GS-9131 in HIV, but the asset recently quietly slipped off its pipeline.

Diana Brainard, SVP, HIV and emerging viral infections at Gilead, told investors the elimination of GS-9131 from the pipeline reflects the rise of GS-6207, a capsid inhibitor that came through phase 1b earlier this year. The data have persuaded Gilead to back GS-6207 at the expense of GS-9131.

“Because of this novel mechanism of action, because of the potency, because of the lack of pre-existing resistance, we really feel that the capsid inhibitor is the really best and lead compound to bring forward in highly-treatment-experienced patients,” Brainard said.

Other pipeline updates included the penciling in of a 2020 start date for Kite’s allogeneic anti-CD19 CAR-T KITE-037. Last year, Gilead expressed hopes that it would file an IND for an allogeneic CAR-T in 2019.