Dupilumab on the verge of becoming first targeted therapy in atopic dermatitis.
By Anna Reyes, Analyst
10 June 2016
I am an Immunology & Inflammation analyst at Datamonitor Healthcare, based in the London office. I joined Datamonito...
Read full bio
Regeneron and Sanofi’s dupilumab has met the primary and key secondary endpoints in its year-long LIBERTY AD CHRONOS Phase III study, reaffirming its likely status as the first targeted therapy to be approved for use in atopic dermatitis (AD) patients refractory to existing treatments. In combination with topical corticosteroids (TCS), dupilumab demonstrated superiority to TCS monotherapy as measured by improvements in overall disease severity, such as skin clearing and itching, with efficacy being sustained through to week 52. The promising one-year data strengthen earlier results from dupilumab’s Phase III LIBERTY AD SOLO studies, where dupilumab monotherapy significantly improved measures of overall disease severity compared to placebo, and will support the drug’s Biologic License Application in the US in Q3 2016.
On 6 June 2016, Regeneron and Sanofi announced that dupilumab, a fully human monoclonal antibody that blocks signaling from both interleukin (IL)-4 and IL-13, had met the primary and key secondary endpoints in the LIBERTY AD CHRONOS study in AD. The trial included a total of 740 patients, and aimed to evaluate the efficacy and long-term safety of dupilumab in combination with TCS in adult patients with moderate-to-severe AD, who were inadequately controlled by TCS with or without topical calcineurin inhibitors.
Dupilumab provided clinically significant improvements in measures of overall disease activity compared to placebo at weeks 16 and 52. At week 16, 39% of patients treated with dupilumab 300mg weekly or biweekly achieved clearing (investigator’s global assessment [IGA] score of 0) or near-clearing (IGA 1) of skin lesions, compared to 12% of patients in the placebo group (p<0.0001). Additionally, 64% of patients treated with dupilumab 300mg weekly, and 69% of patients treated with dupilumab 300mg biweekly, achieved an Eczema Area and Severity Index (EASI) 75 response. Only 23% of patients in the placebo group achieved EASI 75 at week 16 (p<0.0001). At week 52, 40% of patients treated with dupilumab 300mg weekly and 36% of patients treated with dupilumab 300mg biweekly achieved an IGA score of 0 or 1, compared to 12.5% of patients in the placebo group (p<0.0001). Furthermore, 64% of patients treated with dupilumab 300mg weekly, and 65% of patients treated with dupilumab 300mg biweekly achieved an EASI 75 response, compared to 22% of patients in the placebo group (p<0.0001).
Dupilumab also demonstrated a positive safety and tolerability profile. A greater proportion of patients in the placebo group (33%) discontinued therapy, compared to patients in the two dupilumab groups (15%), while the overall rate of adverse events was comparable between all groups. Injection site reactions constituted the most common adverse event observed in the dupilumab groups.
Dermatologists interviewed by Datamonitor Healthcare indicate a positive outlook for dupilumab based on its mechanism of action, and eagerly anticipate its approval as the first targeted therapy for use in AD. While dermatologists note that they are generally satisfied with the non-specific anti-inflammatory topical agents that are the mainstay of therapy for AD, they highlight that there is a significant need for targeted therapies that allow more effective management of patients who are refractory to existing options. In November 2014, the US Food and Drug Administration granted dupilumab breakthrough therapy designation for the treatment of moderate-to-severe AD, which was based on the drug’s positive Phase I and Phase II data, as well as its potential to provide significant improvements over available therapies in this difficult-to-treat patient subgroup.
While dupilumab is likely to be approved for use in patients with moderate-to-severe AD, Datamonitor Healthcare believes that its anticipated high cost in a market where low-cost topical therapies are the mainstay of treatment will result in access being restricted to patients with the greatest need. Based on discussions with key opinion leaders, a cost-effective approach to the use of dupilumab could result in the biologic being used in combination with TCS for a short period of time in order to induce remission of the disease, followed by continuation with maintenance TCS monotherapy. Nevertheless, dupilumab’s expected high price will also mean that Sanofi and Regeneron will see relatively high returns, despite low patient numbers.
Get your free demo of Datamonitor Healthcare today. Simply fill out the form to the right >>>