Gilead confirms plan to file filgotinib this year – Trust favourite Gilead (NASDAQ: GILD) announced yesterday that it expected to file its closely watched JAK1 inhibitor filgotinib – which is licensed from the Belgian biotech Galapagos (NASDAQ:GLPG) – in the key indication of rheumatoid arthritis (RA) later this year, up to 12 months ahead of the timeline assumed by analysts. Gilead is a core holding for Biotech Growth Trust (BIOG, 5.1% of NAV), International Biotechnology Trust (IBT, 7.1% – its largest single holding) and BB Biotech (BION, 1.9% of NAV).
The drug has largely completed its Phase III trial programme in RA, but the filing was throught to be dependent on the outcome of an ongoing Phase II study of testicular safety in men with moderately to severely active ulcerative colitis or Crohn’s disease known as “MANTA”. The change to the timeline was based on the outcome of a pre-NDA meeting with the US FDA and, it is assumed, this means that the application now does not require the completion of MANTA. This study, which tests whether drug causes reduction in semen quality (sperm concentration), is thought to be difficult to recruit patients for as its inclusion criteria require endoscopy confirmed moderate-to-severe UC and a below “normal” sperm count. There is also competition from other studies in UC/Crohn’s and the various alternative approved treatments for the conditions. Most analysts specuilate that the regulator has allowed Gilead to file with interim data from the study and/or allowed it to use a rolling NDA so that the MANTA data can be added later in the review.
There is intense interest from investors in the competition between filgotinib and AbbVie’s updacitinib, another JAK1-selective inhibitor, which was filed for RA in December last year. As an indication of the prize, AbbVie has used a priority review voucher – a type of regulatory trump card which confers a fast regulatory review time that costs ~$100m. As a result, AbbVie expects a US regulatory decision by September this year and planned to launch and gain market share ahead of Gilead.
Both filgotinib and upadacitinib are JAK1 selective, which should give them an advantage over the first generation JAK1/2 ihbitors, Xeljanz (Pfizer) and Olumiant (Lilly), which carry blockbox warnings and/or have other safety issues. Analysts currently project upadacitinib to become the lead in the class with consensus peak revenues of $2bn or more, with filgotinib lower in the region of $1.5bn/year. Both drugs are in development for multiple autoimmune indications.
However, outside of RA these two could face considerable competition longer term from the putative TYK2 class (including dual TYK2/JAK1 inhibitors). Bristol-Myers Squibb is the lead position with BMS-986165 (a pure TK2i), which is in Phase III trials for plaque psoriasis and Phase II studies for UC/Crohns’s, psoriatic arthritis and lupus. It is followed by Pfizer’s dual inhibitor PF-06700841, which is in Phase II studies for all of the same indications as well as vitiligo. Galapagos and AbbVie have TYK2 inhibitors in early clinical development and the UK’s Sareum (SAR) and the private US firm Nimbus Therapeutics, have preclinical molecules.