Products

Date: 2018-01-22

Type of information: Granting of a Market Authorisation in Japan

Product name: Dupixent®

Compound: dupilumab

Therapeutic area: Dermatological diseases - Inflammatory diseases

Action mechanism:

• monoclonal antibody. Dupilumab, a fully-human monoclonal antibody, is directed against the IL-4 receptor alpha subunit, which blocks signaling from both IL-4 and IL-13. IL-4 and IL-13 are key cytokines that are required for the initiation and maintenance of the Th2 (Type 2 helper T-cell) immune response, which is believed to be a critical pathway in allergic inflammation. Dupilumab was created using Regeneron's pioneering VelocImmune® technology and is being co-developed with Sanofi in atopic dermatitis, asthma and chronic sinusitis with nasal polyps.

Company: Sanofi (France) Regeneron Pharmaceuticals (USA - NY)

Disease: moderate-to-severe atopic dermatitis

Latest news:

• • On January 22, 2018, Regeneron Pharmaceuticals announced that the Ministry of Health, Labor and Welfare (MHLW) in Japan has granted marketing and manufacturing authorization for Dupixent® (dupilumab) for the treatment of atopic dermatitis in adults not adequately controlled with existing therapies. Dupixent® will be commercialized in Japan by Sanofi.
• • On July 20, 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Dupixent®, intended for the treatment of atopic dermatitis. The benefits with Dupixent® are its ability to improve the skin condition as measured by improvements in the IGA and EASI-75 scales and to reduce itching in patients with atopic dermatitis. The most common side effects are injection site reactions, conjunctivitis, blepharitis, and oral herpes. The full indication is: "Dupixent® is indicated for the treatment of moderate-to-severe atopic dermatitis in adult patients who are candidates for systemic therapy".
• The drug will come in a pre-filled syringe for self-administration by a patient as a subcutaneous injection every other week after an initial loading dose. Dupixent® can be used with or without topical corticosteroids.
• The CHMP opinion is based on studies from the global LIBERTY atopic dermatitis clinical trial program, including SOLO 1, SOLO 2, SOLO-CONTINUE,CHRONOS and CAFÉ. These studies incorporated data from nearly 3,000 adult patients with moderate-to-severe atopic dermatitis not adequately controlled with topical prescription therapies or immunosuppressant such as cyclosporine, or when those therapies were not advisable.
• • On March 28, 2017, the FDA approved Dupixent® (dupilumab) injection to treat adults with moderate-to-severe eczema (atopic dermatitis). The drug is intended for patients whose eczema is not controlled adequately by topical therapies, or those for whom topical therapies are not advisable. It can be used with or without topical corticosteroids.
• The safety and efficacy of Dupixent® were established in three placebo-controlled clinical trials with a total of 2,119 adult participants with moderate-to-severe atopic dermatitis not adequately controlled by topical medication(s). Overall, participants who received Dupixent® achieved greater response, defined as clear or almost clear skin, and experienced a reduction in itch after 16 weeks of treatment.
• The approval of Dupixent® was based on data from the global LIBERTY AD clinical program, which included three randomized Phase 3 pivotal trials known as SOLO 1, SOLO 2 and CHRONOS (enrolled 2,119 total adult patients). The studies examined the use of Dupixent® either alone (SOLO 1 or SOLO 2, 1,379 adult patients enrolled) or with topical corticosteroids (CHRONOS, 740 adult patients enrolled) in patients with inadequately controlled moderate-to-severe AD. In all these studies, Dupixent® alone or with topical corticosteroids met the primary and key secondary endpoints, specifically:
• In the SOLO 1 and SOLO 2 studies, treatment with Dupixent® as monotherapy significantly improved measures of skin clearing and overall extent and severity of disease: At 16 weeks, for SOLO 1 and SOLO 2, respectively, 38 and 36 percent of patients who received Dupixent® 300 mg every two weeks achieved clear or almost clear skin as measured by the 5-point Investigator's Global Assessment (IGA) scale (primary endpoint), compared to 10 and 9 percent with placebo.
• At 16 weeks, for SOLO 1 and SOLO 2, respectively, 51 and 44 percent of patients who received Dupixent® 300 mg every two weeks achieved a 75 percent or greater reduction in their Eczema Area and Severity Index score (EASI-75) from baseline, a key secondary endpoint, compared to 15 and 12 percent with placebo.
• At 16 weeks, for SOLO 1 and SOLO 2, respectively, 41 and 36 percent of patients who received Dupixent® 300 mg every two weeks achieved a greater than or equal to 4 point improvement in the daily intensity of patient-reported itch, as measured by the Pruritus Numerical Rating Scale (NRS), compared to 12 and 10 percent with placebo.
• In the CHRONOS study, treatment with Dupixent with topical corticosteroids (TCS) significantly improved measures of overall disease severity at 16 and 52 weeks, when compared to placebo with TCS:
• - At 16 weeks, 39 percent of patients who received Dupixent 300 mg every two weeks with TCS achieved clear or almost clear skin (IGA 0 or 1), the primary endpoint, compared to 12 percent of patients receiving placebo with TCS.
• - At 16 weeks, 69 percent of patients who received Dupixent® 300 mg every two weeks with TCS achieved EASI-75 (key secondary endpoint), a 75 percent reduction on an index measuring eczema severity, compared to 23 percent of patients receiving placebo with TCS.
• - At 16 weeks, 59 percent of patients who received Dupixent® 300 mg every two weeks with TCS achieved a greater than or equal to 4 point improvement in the daily intensity of patient-reported itch, as measured by the NRS, compared to 20 percent of patients receiving placebo with TCS.
• The study also met additional key secondary endpoints at 52 weeks, showing that 36 percent of patients who received Dupixent 300 mg every two weeks with TCS achieved clear or almost clear skin (IGA 0 or 1), compared to 13 percent of patients receiving placebo with TCS. The most common adverse events that were noted to be greater than or equal to one percent with Dupixent® treatment included injection site reactions, eye and eye lid inflammation including redness, swelling, and itching, and cold sores in the mouth or on the lips.
• Sanofi Genzyme, the specialty care global business unit of Sanofi, and Regeneron will market Dupixent® in the United States. Dupixent is expected to be available to patients and providers in the U.S. later this week.
• Sanofi and Regeneron recognize that Dupixent® can only help those uncontrolled moderate-to-severe AD patients that were prescribed the medicine if they can both access the medicine and use it properly. Therefore, the companies have launched Dupixent MyWay™, a comprehensive and specialized program that provides support and services to patients throughout every step of the treatment process.
• Dupixent MyWay™ will help eligible patients who are uninsured, lack coverage, or need assistance with their out-of-pocket costs. Additionally, Dupixent MyWay™ offers personalized support from registered nurses and other specialists who are available 24/7 to speak with patients and help them navigate the complex insurance process.
• The Wholesale Acquisition Cost (WAC) of Dupixent® in the United States is $37,000 annually. Actual costs to patients, payers and health systems are anticipated to be lower as WAC pricing does not reflect discounts, rebates or patient assistance programs.
• • In December 2016, the European Medicines Agency accepted for review Sanofi's and Regeneron's marketing authorization application (MAA) for Dupixent for adults with uncontrolled moderate-to-severe AD.
• • On September 26, 2016, Regeneron Pharmaceuticals and Sanofi announced that the FDA has accepted for priority review the Biologics License Application (BLA) for dupilumab (Dupixent®) for the treatment of adult patients with inadequately controlled moderate-to-severe atopic dermatitis. The application has been given a Prescription Drug User Fee Act (PDUFA) target action date of March 29, 2017. Dupilumab inhibits signaling of IL-4 and IL-13, two key cytokines required for the type 2 (including Th2) immune response, which is believed to be a major driver in the pathogenesis of the disease.
• The BLA for dupilumab contains data from three Phase 3 pivotal studies in the global LIBERTY AD program that included more than 2,500 patients. The goal of the studies was to evaluate dupilumab as monotherapy (SOLO 1 and SOLO 2 ) and in concomitant administration with topical corticosteroids (CHRONOS ), in adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies. In 2014, the FDA granted Breakthrough Therapy designation to dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis who are not adequately controlled with topical prescription therapies or for whom these treatments are not appropriate.
• • On November 20, 2014, Regeneron Pharmaceuticals and Sanofi announced that the FDA has granted Breakthrough Therapy designation to dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis who are not adequately controlled with topical prescription therapy and/or for whom these treatments are not appropriate. Dupixent represents the first time this designation was granted for a dermatological disease, other than in dermatologic cancers.
• The designation is based on positive results from Phase 1 and 2 clinical trials. A Phase 3 worldwide clinical program for dupilumab in adults with moderate-to-severe atopic dermatitis is ongoing.

Patents:

Submission of marketing authorization application USA :

Submission of marketing authorization application UE:

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2017-03-28

UE authorization: 2017-09-26

Favourable opinion UE: 2017-07-20

Favourable opinion USA:

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes