provide an alternative to injectable treatments like AbbVie’s (NYSE: [[ticker:ABBV]]) adalimumab. That drug, which suppresses the immune system, can also leave patients more vulnerable to potentially deadly infections.
There are other drugs that work by targeting JAK enzymes. The first such drug, tofacitinib (Xeljanz) from Pfizer (NYSE: [[ticker:PFE]]), received the FDA’s nod in 2012 for treating patients with moderate to severe RA who haven’t responded to or can’t take methotrexate, a chemotherapy that is also among the first-line treatments for arthritis. By comparison, Lilly is aiming to treat all adults with moderate to severe RA. Other experimental JAK inhibitors are trailing the Lilly drug. AbbVie’s upadacitinib and the Gilead Sciences (NASDAQ: [[ticker:GILD]]) drug filgotinib are in late-stage RA studies.
The most common side effect observed in patients treated with baricitinib was infection, such as respiratory and urinary tract infections. The FDA documents state that the Lilly drug was associated with an increase in platelet count, which was in contrast to other approved JAK inhibitors that are associated with decreases in platelet counts. The platelet increases were greater at the higher dose of baricitinib.
In the analysis of all patients treated with the Lilly drug, platelet counts in four of them were high enough to be characterized as thrombocytosis, a condition in which the body produces too many platelets. But the documents also say those high platelet levels could be due to a number of causes. One patient was reported to have a blood clot, though the documents add there was no clear relationship between the elevated platelet levels and the blood clot. Though FDA reviewers could not link JAK inhibition to elevated platelet levels, they noted that baricitinib didn’t have a safety advantage: its risks were consistent with drugs like adalimumab.
The comparison to adalimumab might be the wrong one. Lilly argued in its submission that its drug’s approach of targeting two specific JAK enzymes would offer a lower risks compared to other drugs that suppress the immune system. But one of the reviewers said that the opposite might be true. Elevated platelets and blood clot risks were observed in some of the patients treated with barictinib but not in studies testing Pfizer’s drug, the reviewer wrote. In a research note, Leerink analyst Geoffrey Porges said that that the FDA briefing documents suggest that the safety standard set by Pfizer’s JAK inhibitor is the mark that the Lilly drug and other second-generation JAK inhibitors must beat.
Barclays analyst Brian Abrahams pointed out in a research note that that the three FDA reviewers who wrote the briefing document had different views about the risks and benefits of baricitinib. Those views could lead the advisory panel to take a “middle ground” approach, recommending approval of the 2 mg dose. That outcome would be considerably less lucrative for Lilly because at that dose, the drug was not superior to AbbVie’s drug in head-to-head tests, Abrahams said.
The advisory panel will vote on seven questions regarding baricitinib, including whether the safety data submitted by Lilly are enough to support approval of the drug at either the 2 mg or 4 mg doses.
Photo by Flickr user Ann Gordon via a Creative Commons license
