Pfizer’s atopic dermatitis drug bests dupilumab, but only at higher dose

Reuters Health - 24/03/2021 - In patients with moderate to severe atopic dermatitis, treatment with abrocitinib reduces symptoms better than placebo, but only the higher 200 mg dose was superior to dupilumab in a new test of 838 adults reported in The New England Journal of Medicine.

The benefits were seen even though all the volunteers were receiving background therapy with topical medications.

One primary endpoint of the study, known as JADE COMPARE, relied on the 5-point Investigator's Global Assessment (IGA) survey. The researchers were looking for an improvement of at least 2 points. They saw it by week 12 in 48.4% of patients getting the 200 mg dose, 36.6% getting 100 mg daily, 36.5% of those getting dupilumab injections, but only 14.0% in the placebo group.

The other 12-week endpoint used the 73-point Eczema Area and Severity Index-75 (EASI-75), where a 75% improvement in the baseline score was seen in 70.3% getting high-dose abrocitinib, 58.7% in patients receiving the lower dose of the drug, 58.1% with dupilumab and 27.1% with placebo.

"The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2, but neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end points at week 16," said the team, led by Dr. Thomas Bieber of the University Hospital of Bonn in Germany.

Dr. Bieber did not respond to requests for comment.

Abrocitinib is an experimental oral selective inhibitor of Janus kinase 1. Dupilumab, sold under the brand name Dupixent by Sanofi and Regeneron Pharmaceuticals, Inc., is administered by subcutaneous injection; it costs about $4,000 a month.

Pfizer paid for the study and collected and analyzed the data. The company announced top-line results -- but revealed no data -- on March 18, 2020. An FDA decision on the drug could come next month..

The researchers also looked for a reduction in itch based on an improvement of at least 4 points on the 0- to 10-point Peak Pruritus Numerical Rating Scale. At the two-week mark in the study, 13.8% of placebo recipients achieved that goal compared with 26.4% of those getting dupilumab, 31.8% of volunteers given 100 mg abrocitinib and 49.1% in the 200 mg abrocitinib group.

However, while the effectiveness of both doses of abrocitinib seemed to plateau after eight weeks based on the primary endpoint metrics, the number of volunteers responding to dupilumab continued to increase over the 16 weeks that the drug was studied.

"Both doses of abrocitinib were not significantly different from dupilumab with respect to an EASI-75 response at week 16," the Bieber team said. The same was true for data from the IGA survey.

But by both metrics, the team asserted, no clinical inferences could be made from that data because the end points were not adjusted for multiple comparisons.

There were no obvious trends in the rates of severe and serious adverse events.

However, nausea rates were 1.5% with placebo, 2.9% with dupilumab, 4.2% with lower-dose abrocitinib and 11.1% with the higher dose of the test drug.

The other key side effect was acne, seen in none of the placebo patients, 3 of the 242 volunteers getting dupilumab, 7 of the 238 who got low-dose abrocitinib and 15 of the 226 who got the higher dose of the drug.

"Herpes zoster was reported more frequently with abrocitinib than with placebo or dupilumab, and serious infections occurred in two patients receiving abrocitinib," the researchers said.

Data from two previous studies -- JADE MONO-1 and JADE MONO-2 -- have also shown a significant benefit of abrocitinib over placebo.

Atopic dermatitis affects as many as 10% of adults and up to 20% of children worldwide.

SOURCE: https://bit.ly/313Rrua The New England Journal of Medicine, online March 24, 2021

By Reuters Staff



Posted on 24 March 202130 March 2021