A novel experimental drug is showing promising results from its final phase of human clinical trials. Part of a new class of drugs called JAK-inhibitors, this therapy targets rheumatoid arthritis sufferers and is hoped to be approved for use by the FDA within the next 12 months.
The JAK family consists of four closely related molecules: JAK1, JAK2, JAK3 and TYK2, which play a pivotal role in facilitating cellular inflammatory signals. Over the past decade a new class of drugs known as JAK inhibitors have been in development as prospective treatments for a number of different immune-meditated diseases, from eczema to inflammatory bowel diseases such as Crohn's.
Back in 2011/12, two JAK inhibitors initially hit the market. These first-generation iterations have been found to be somewhat effective but their lack of specificity can trigger a variety of negative side effects. The latest generation of JAK inhibitors are now reaching the final stages of human clinical trials. Designed to more narrowly inhibit individual JAK molecules, these new drugs are hoped to be more effective with fewer adverse effects.
Filgotinib is a JAK inhibitor that selectively targets the JAK1 enzyme. It is primarily being investigated to treat rheumatoid arthritis but initial clinical trials have shown promise treating both ulcerative colitis and Crohn's disease. After years of development scientists are this week publishing some of the first results from the final Phase 3 human trials into the efficacy of the new drug, ahead of an FDA application to move the drug to market by 2020.
The results are certainly promising, with over 40 percent of subjects on the highest dose of filgotinib reporting "low disease activity" after 12 weeks, compared to only around 15 percent reporting similar effects on a placebo. By 24 weeks of use this success rate had increased to nearly 50 percent. Even more impressively, 30 percent of the high-dose filgotinib group achieved full disease remission after 24 weeks, compared to just 12 percent on placebo.
Mark Genovese, principle investigator on the research, suggests these results are better than any of the current first-generation JAK inhibitors already clinically available. He also notes that the new drug seems effective regardless of any other treatments a patient had previously failed. This is unlike traditional biologic treatments for rheumatoid arthritis where subsequent therapies are rarely as efficacious as the first therapy a patient is administered.
"We found that those high levels of response were independent of how many drugs you'd failed, and independent of which drugs you'd failed," says Genovese.
But all isn't perfect in the world of filgotinib, with some questioning the overall safety of the new drug. Concerns were raised late in 2018 suggesting the drug could cause testicular damage in men, and lower sperm counts. The FDA subsequently requested an additional safety study be conducted to evaluate this particular risk. It is unclear whether this extra trial will delay the hopeful 2020 launch of the drug but Gilead, the pharmaceutical company developing the drug, announced earlier this month that all is confidently on track for FDA approval in the near future.
It is unclear how much filgotinib may cost when it eventually hits the market but it will certainly have some competition. A rival JAK1 inhibitor called upadacitinib was granted priority review by the FDA earlier this year signaling its impeding approval sometime later in 2019. This means filgotinib may not win the race to be the first new-generation JAK1 inhibitor to reach the market, but it will mean those suffering from severe rheumatoid arthritis should have several new therapeutic options to choose from over the next 12 months.
The new research was published in the journal JAMA.
Source: Stanford Medicine