Dupixent (dupilumab), the first biologic approved for atopic dermatitis (AD), hasn’t shaken up treatment of the condition completely even as it steadily gains market share, since the bulk of plans still require patients to try mostly generic topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs) first. But more competition could be coming to this category, with the FDA set to consider four new products for AD, including three Janus kinase (JAK) inhibitors.
The oral JAK inhibitors hit a speed bump in April: The FDA extended the review period to early in the third quarter of 2021 for Pfizer Inc.’s abrocitinib for the treatment of adults and adolescents with moderate to severe AD. The agency also extended review to the third quarter of Eli Lilly and Co.’s and Incyte’s supplemental New Drug Application for Olumiant (baricitinib) for the treatment of adults with moderate to severe AD, saying it wants to gather additional cost-benefit and safety data.
Meanwhile, the FDA requested additional data on LEO Pharma A/S’s biologic tralokinumab, intended for adults with moderate to severe AD, but only on a device component, not on efficacy or safety, the company said in April. The European Union’s Committee for Medicinal Products for Human Use recommended approval of tralokinumab in April.
Finally, a topical JAK inhibitor, Incyte’s ruxolitinib, was accepted for FDA priority review in February, with a target FDA action date in late June.
“The new oral and injectable therapies may bring new formulary options compared to Dupixent,” says Mesfin Tegenu, CEO and chairman, RxParadigm, a pharmacy benefit cost management start-up focused on providing tools and transparency. “Depending upon how these new products are priced, market forces may play a role to bring down the annual cost for Dupixent. However, for any responsible prescriber there’s an abundance of generic topical corticosteroids available for treatment.”
Efficacy for abrocitinib “appears similar to the existing standard (Dupixent),” according to the latest quarterly Drug Pipeline Insights Report from UnitedHealth Group’s OptumRx. “Note that currently approved JAK inhibitors have ‘boxed warnings’ for serious side effects that may also apply to abrocitinib,” the report said. Olumiant, approved for rheumatoid arthritis, carries a black box warning for the risk of infections, malignancy and thrombosis.
OptumRx noted that tralokinumab would offer a novel mechanism of action for AD. “Available evidence is that its efficacy appears more modest than competing existing treatment options like Dupixent,” the report said. “Note that tralokinumab, like Dupixent, is given by subcutaneous injection, while newer JAK inhibitors would be oral or creams.”
If approved, ruxolitinib would be the first topical JAK inhibitor to treat mild-to-moderate AD in patients ages 12 and older, OptumRx’s report pointed out. “Mild-to-moderate is a much larger population than moderate-to-severe, but it is also easier to treat with existing drugs such as Pfizer’s topical Eucrisa,” the PBM said. “Efficacy for ruxolitinib is promising, but there is currently no data directly comparing ruxolitinib against other AD agents. The topical form may reduce some of the safety concerns associated with oral JAK inhibitors.”
The wholesale acquisition cost of Dupixent, from Sanofi and Regeneron Pharmaceuticals, Inc., is approximately $41,000 per year. Sanofi reported in February that Dupixent sales rose nearly 74% in 2020 compared with 2019, and attributed the sales growth to rapid adoption of the drug in children ages 6 to 11. Dupixent was approved in May 2020 for use in that age group. “Dupixent total prescriptions increased 65% (year-over-year) and new-to-brand prescriptions grew 18% despite fewer in-person physician, visits which remain below the pre-COVID level,” Sanofi said in its earnings release.
The list price of Olumiant is $2,378.40 per month for 2 mg tablets, or more than $28,500 a year, according to Eli Lilly.
Awareness of Condition Is Increasing
The other recent entrant to the AD category, Eucrisa (crisaborole), a steroid-free topical treatment from Palo Alto, Calif.-based Anacor Pharmaceuticals, Inc., costs around $700 per month, or $8,400 per year.
At Prime Therapeutics, Dupixent is preferred on the PBM’s standard formulary as a specialty medication, says April Kunze, Pharm.D., senior director of clinical program development. It is subject to utilization management, including step therapy and dispensing limits, Kunze says, adding, “there has been more awareness to this category, and biologics such as Dupixent have been approved with good efficacy results.”
Meanwhile, Eucrisa is preferred on Prime’s standard A-Series NetResults formulary with no utilization management in place, Kunze tells AIS Health.
The brand-name drugs in the pipeline, if approved, will compete for a small slice of the overall AD patient population, Kunze points out: “According to Sanofi/Regeneron, there are approximately 300,000 adults with uncontrolled moderate-to-severe AD patients in the U.S. that may utilize Dupixent, which is about 5% of the moderate-to-severe AD population. This is the same population that may utilize the oral and injectable biologics that are currently being reviewed by the FDA.”
“The majority of patients are diagnosed with mild to moderate atopic dermatitis,” Tegenu says. Patients who require additional treatment following or as an alternative to systemic immunosuppressive therapy may then require a biologic, he points out.
Plans may treat Dupixent and Eucrisa as preferred or non-preferred, and typically require utilization management such as step therapy or prior authorization, Tegenu says.
Kunze notes that, if approved, ruxolitinib cream will be the first topical biologic for mild-to-moderate AD. “The anticipated place in therapy is after first-line treatments but before a systemic biologic,” she says.
The newer agents, while potentially beneficial to a subset of patients, are unlikely to shake up treatment of most patients, according to Tegenu. “Treatment starts with the more conventional options, as there is much more data available and cost is significantly lower,” Tegenu says. “Topical corticosteroids (TCS) and emollients continue to be the mainstay treatment to which other topical therapies are compared to. Additionally, with TCS agents, there are many different options based on level of potency and formulation that can be selected depending on patient-specific criteria, such as age and body area. TCIs [topical calcineurin inhibitors] are appropriate alternatives for sensitive areas in mild to moderate cases.”
Tegenu adds, “these newer agents are typically reserved for when a patient fails or is not a candidate for the alternative.” According to the American Academy of Dermatology, therapy first progresses through topical agents, then through systemic agents, and then to a biologic agent if systemic agents fail. Phototherapy, which generally is covered under the medical benefit, can be considered if topical agents fail, although coverage varies by plan (see infographic, p. 4).
New Entrants Won’t Lower Plan Costs
Kunze says some patients may benefit from additional options, but plans may not see much savings. In addition, she suggests that the FDA’s delay in approving abrocitinib and baricitinib could impact their sales.
“There is potential to create competition for Dupixent. However, given the current pricing of JAK inhibitors, these may not bring down the overall cost of therapy. Because JAK inhibitors provide an oral option, they may appeal to some atopic dermatitis patients who do not want to administer an injectable like Dupixent. However, considering the JAK inhibitors’ extended FDA decision dates and the safety issues surrounding JAK inhibitors, and their potential higher cost compared to Dupixent, they may have a difficult time garnering significant market share.”
by Jane Anderson