Late-breaking data presented at the annual meeting offers hope for the first dedicated treatment outside of corticosteroids.
Dupilumab significantly improved symptoms and disease activity in patients with bullous pemphigoid, according to late-breaking pivotal data presented at the American Academy of Dermatology’s annual meeting in Florida earlier this month.
Five times more adults using the monoclonal antibody achieved sustained disease remission at 36 weeks compared to placebo, with significant reductions also seen in disease severity and itch.
Dupilumab also significantly lowered the use of oral corticosteroids and rescue medications compared to placebo, the pivotal ADEPT phase 2/3 study evaluating the investigational use dupilumab in adults with moderate-to-severe BP has found.
BP is a chronic, debilitating and relapsing skin disease with underlying inflammation and characterised by intense itch and blisters, skin redness and painful lesions.
In the ADEPT study, 106 adults with moderate-to-severe BP were randomized to receive dupilumab 300 mg (n=53) every two weeks after an initial loading dose or placebo (n=53), along with standard-of-care oral corticosteroids (OCS). During treatment, all patients underwent a protocol-defined OCS tapering regimen if control of disease activity was maintained.
Sydney dermatologist Professor Dedee Murrell, head of the Department of Dermatology at St George Hospital and the University of NSW, has been involved in the design and conduct of the international trial since the outset.
Professor Murrell said it was an exciting step forward in providing these patients with access to the drug, and that the results were being submitted for publication at a peer-reviewed journal.
“It’s an important development,” Dr Murrell told Dermatology Republic.
“Bullous pemphigoid has such a high mortality; it’s about 23% and that’s partly because it occurs predominantly in people aged 70 to 80 to 90 years.”
Professor Murrell said one of the biggest challenges to treating the disease at the current point in time was that treatment options are limited supportive care and OCS, which are not ideal for frail or elderly patients.
“There are so many horrible side effects [with OCS]. And even if you get on it, you’re on it for four to six weeks at high doses to get the disease under control, and then a minimum of four months to taper down the dose,” she said.
“And then, typically, at least, at least half the patients relapse. Many patients can’t cope with the itch and the weepy wounds, and they get infections and that brings more challenges.”
She said patients using dupilumab in the trial had a five times higher rate of coming completely off steroids for 20 weeks.
As presented at AAD, results for dupilumab-treated patients at 36 weeks, compared to those treated with placebo, were as follows:
- 20% experienced sustained disease remission, the primary endpoint, compared to 4% (p=0.0114).
- 40% achieved ≥90% reduction in disease severity compared to 10% (p=0.0003).
- 40% achieved clinically meaningful itch reduction compared to 11% (p=0.0006).
- 1678mg reduction in cumulative oral corticosteroid exposure (p=0.0220) on average and a 54% lower risk of rescue medication use (p=0.0016).
Overall rates of adverse events were 96% (n=51) for dupilumab and 96% (n=51) for placebo. AEs more commonly observed with dupilumab compared to placebo in at least three patients included peripheral oedema (n=8 vs. n=5), arthralgia (n=5 vs. n=3), back pain (n=4 vs. n=2), blurred vision (n=4 vs. n=0), hypertension (n=4 vs. n=3), asthma (n=4 vs. n=1), conjunctivitis (n=4 vs. n=0), constipation (n=4 vs. n=1), upper respiratory tract infection (n=3 vs. n=1), limb injury (n=3 vs. n=2) and insomnia (n=3 vs. n=2).
There were no AEs leading to death in the dupilumab group and two AEs leading to death in the placebo group.
Professor Murrell told DR that while BP was a rare condition, Australia’s ageing population meant more cases were being seen. But she said many cases were going undiagnosed given the similarity with other conditions like scabies and hives.
Having a treatment like dupilumab available would help raise awareness of the disease and offer better patient outcomes.
“A lot of patients present to the emergency department, and they end up getting admitted, and they stay in hospital a lot, and if they don’t go into hospital, they’re out there on a lot of prednisone, having fractures, having diabetes, having infections,” she said.
“Having a treatment like this would help keep them out of hospital. And not only is that improving outcomes but reducing care costs.”
Professor Victoria Werth, chief of the Division of Dermatology at the Philadelphia Veterans Administration Hospital, professor of Dermatology and Medicine at the Hospital of the University of Pennsylvania and the Veteran’s Administration Medical Centre, and a principal investigator of the study, agreed with Professor Murrell’s comments.
“People with bullous pemphigoid live with unrelenting itch, blisters, and painful lesions that can be debilitating and make it difficult to function daily,” she said.
“Moreover, current treatment options can be challenging for this primarily elderly patient population because they work by suppressing their immune system.
“By targeting the underlying type 2 inflammation, which is a key driver for bullous pemphigoid, Dupixent is the first investigational biologic to show sustained disease remission and reduce disease severity and itch compared to placebo in a clinical study.”
Dupilumab is currently listed on the Pharmaceutical Benefits Scheme in Australia for the treatment of patients aged 12 years and above with severe atopic dermatitis who have failed to respond to optimally prescribed topical treatments.
Regulatory submissions for the drug are currently under review in both the US and the EU to expand approvals for its use in BP. Dupilumab was previously granted orphan drug designation by the FDA for BP, which applies to investigational medicines intended for the treatment of rare diseases that affect fewer than 200,000 people in the US.
Dermatology Republic approached Sanofi, which provides the drug under the brand name Dupixent in Australia, for a comment on when it plans to apply to the Therapeutic Goods Administration for approval to treat BP. It provided a brief statement in response.
“Due to commercial confidentiality, we are unable to provide a timeframe for when Dupixent might be indicated for BP in Australia,” a spokesman said.
