FDA Approves a New Oral Drug for Moderate to Severe RA
People with moderate to severe
rheumatoid arthritis (RA)
who haven’t responded well to one or more tumor necrosis factor (TNF) inhibitor medications now have a new option. The U.S. Food and Drug Administration (FDA) recently approved baricitinib (
Olumiant
), a pill that is taken once a day.
Baricitinib is a targeted disease-modifying antirheumatic drug (DMARD) that blocks Janus kinase (JAK), a group of enzymes that enable inflammatory signals to be activated inside a cell. It’s the second in this class of drug to hit the market for the treatment of RA; tofacitinib ( Xeljanz ) was the first, approved in 2012.
“It’s not a biologic but a ‘small molecule,’ or oral, targeted agent, that is highly effective in treating the signs and symptoms of RA,” explains Paul Howard, MD, a rheumatologist in Scottsdale, AZ. It is expected to be significantly cheaper than biologic medications.
Baricitinib maker Eli Lilly and Company had sought approval for both a 2 mg dose and a 4 mg dose, but the FDA approved it at the end of May 2018 only at a 2 milligram (mg) dose. The agency expressed concerns about cases of deep vein thrombosis (DVT) in clinical trials in patients taking the 4 mg dose. DVT is a blood clot that forms in a deep vein, usually in the leg. It can cause swelling, redness and pain, and can break loose and travel to the lung, which can be fatal.
Donald Miller, PharmD, a professor of pharmacy practice at North Dakota State University, in Fargo, was on the FDA Arthritis Advisory Committee when it considered Eli Lilly’s application for baricitinib in late April. He voted for approval of the 2 mg dose and against approval of the 4 mg dose.
“There weren’t enough patients [in the trials] on either dose to be sure of the real rate of deep vein thrombosis, but the best conclusion we could arrive at is the 2 mg dose provided most of the efficacy of the 4 mg dose and probably less of the deep vein thrombosis risk,” Miller explains.
Baricitinib will carry a boxed warning about the risk of thrombosis (blood clots) as well as serious infections and malignancies. Its main competitor, tofacitinib (also approved at the lower of two doses it applied for), carries a similar boxed warning, minus the thrombosis warning.
“It is an important potential risk that physicians need to be aware of, and we will be educating physicians about this,” says Pete Salzmann, MD, vice president of immunology at Eli Lilly. “Rheumatologists are well aware how to recognize both patients at increased risk for thrombosis and how to monitor for it on an ongoing basis. We take that education seriously.”
Dr. Salzmann says the 4 mg dose is approved in other countries, and Eli Lilly will continue to try to get it approved here, too. “We are working with the FDA to define a path for potential approval of the 4 mg in the U.S.,” he says.
Experts say the overall market for baricitinib might be small, because it was approved for patients who have failed at least one TNF inhibitor, but Dr. Salzmann says those patients need options. “This is a group that physicians tell us has the highest unmet need. Those who have failed anti-TNFs are the most challenged getting to a good clinical outcome,” Dr. Salzmann says.
One benefit of using this drug is that it’s taken orally once a day; by contrast, TNF inhibitors and other biologics are either injected or infused as often as once a week. JAK inhibitors, including baricitinib, “are orally active, not injectables, which is a very nice option,” says David Pisetsky, MD, rheumatologist and professor of medicine at Duke University Medical Center in Durham, NC. “There are many patients who don’t want injections or infusions, so there is a convenience with a one-a-day pill that many would welcome.”
Price will likely be another selling point. Eli Lilly says bariticinib’s annual cost will be $24,930 – Dr. Salzmann says that’s 60 percent less than the leading TNF inhibitor. But the final price a consumer pays depends on many factors, including insurance coverage.
In terms of efficacy, Dr. Salzmann says that in studies, improvements in symptoms were seen as early as one week. “Rapid symptom relief, particularly for patients who have failed one or more therapies, is something they are anxious and excited about. That is a benefit,” he says.
There have been no head-to-head studies comparing baricitinib with tofacitinib. Although they are both JAK inhibitors, Dr. Pisetsky says they do have differences.
“There are a number of enzymes in the JAK family that are inhibited by JAK inhibitors. These two medications inhibit one enzyme in common, but each inhibits another enzyme that is different,” he explains. “It’s not entirely clear if these differences for RA would make that much of a difference in efficacy. Are there patients that will respond to one JAK inhibitor rather than another? Time will tell.”
The FDA says patients shouldn’t combine baricitinib with other JAK inhibitors, biologics or strong immunosuppressants such as the DMARDs azathioprine and cyclosporine, although it can be combined with methotrexate and certain other DMARDs.
Eli Lilly says it will launch baricitinib in the U.S. this month.
Author: Jennifer Davis
Baricitinib is a targeted disease-modifying antirheumatic drug (DMARD) that blocks Janus kinase (JAK), a group of enzymes that enable inflammatory signals to be activated inside a cell. It’s the second in this class of drug to hit the market for the treatment of RA; tofacitinib ( Xeljanz ) was the first, approved in 2012.
“It’s not a biologic but a ‘small molecule,’ or oral, targeted agent, that is highly effective in treating the signs and symptoms of RA,” explains Paul Howard, MD, a rheumatologist in Scottsdale, AZ. It is expected to be significantly cheaper than biologic medications.
Safety Concerns
Baricitinib maker Eli Lilly and Company had sought approval for both a 2 mg dose and a 4 mg dose, but the FDA approved it at the end of May 2018 only at a 2 milligram (mg) dose. The agency expressed concerns about cases of deep vein thrombosis (DVT) in clinical trials in patients taking the 4 mg dose. DVT is a blood clot that forms in a deep vein, usually in the leg. It can cause swelling, redness and pain, and can break loose and travel to the lung, which can be fatal.
Donald Miller, PharmD, a professor of pharmacy practice at North Dakota State University, in Fargo, was on the FDA Arthritis Advisory Committee when it considered Eli Lilly’s application for baricitinib in late April. He voted for approval of the 2 mg dose and against approval of the 4 mg dose.
“There weren’t enough patients [in the trials] on either dose to be sure of the real rate of deep vein thrombosis, but the best conclusion we could arrive at is the 2 mg dose provided most of the efficacy of the 4 mg dose and probably less of the deep vein thrombosis risk,” Miller explains.
Baricitinib will carry a boxed warning about the risk of thrombosis (blood clots) as well as serious infections and malignancies. Its main competitor, tofacitinib (also approved at the lower of two doses it applied for), carries a similar boxed warning, minus the thrombosis warning.
“It is an important potential risk that physicians need to be aware of, and we will be educating physicians about this,” says Pete Salzmann, MD, vice president of immunology at Eli Lilly. “Rheumatologists are well aware how to recognize both patients at increased risk for thrombosis and how to monitor for it on an ongoing basis. We take that education seriously.”
Dr. Salzmann says the 4 mg dose is approved in other countries, and Eli Lilly will continue to try to get it approved here, too. “We are working with the FDA to define a path for potential approval of the 4 mg in the U.S.,” he says.
Experts say the overall market for baricitinib might be small, because it was approved for patients who have failed at least one TNF inhibitor, but Dr. Salzmann says those patients need options. “This is a group that physicians tell us has the highest unmet need. Those who have failed anti-TNFs are the most challenged getting to a good clinical outcome,” Dr. Salzmann says.
Convenience Factor
One benefit of using this drug is that it’s taken orally once a day; by contrast, TNF inhibitors and other biologics are either injected or infused as often as once a week. JAK inhibitors, including baricitinib, “are orally active, not injectables, which is a very nice option,” says David Pisetsky, MD, rheumatologist and professor of medicine at Duke University Medical Center in Durham, NC. “There are many patients who don’t want injections or infusions, so there is a convenience with a one-a-day pill that many would welcome.”
Price will likely be another selling point. Eli Lilly says bariticinib’s annual cost will be $24,930 – Dr. Salzmann says that’s 60 percent less than the leading TNF inhibitor. But the final price a consumer pays depends on many factors, including insurance coverage.
In terms of efficacy, Dr. Salzmann says that in studies, improvements in symptoms were seen as early as one week. “Rapid symptom relief, particularly for patients who have failed one or more therapies, is something they are anxious and excited about. That is a benefit,” he says.
Comparing Drugs
There have been no head-to-head studies comparing baricitinib with tofacitinib. Although they are both JAK inhibitors, Dr. Pisetsky says they do have differences.
“There are a number of enzymes in the JAK family that are inhibited by JAK inhibitors. These two medications inhibit one enzyme in common, but each inhibits another enzyme that is different,” he explains. “It’s not entirely clear if these differences for RA would make that much of a difference in efficacy. Are there patients that will respond to one JAK inhibitor rather than another? Time will tell.”
The FDA says patients shouldn’t combine baricitinib with other JAK inhibitors, biologics or strong immunosuppressants such as the DMARDs azathioprine and cyclosporine, although it can be combined with methotrexate and certain other DMARDs.
Eli Lilly says it will launch baricitinib in the U.S. this month.
Author: Jennifer Davis
