dm+d

34952011000001109

Refrigerated Storage

DupixentSanofi

Sanofi
Dupixent
Solution for injection in pre-filled syinge

In the event of an inadvertent temperature excursion the following data may be used:
If necessary, pre-filled syringes may be kept at room temperature up to 25°C for a maximum of 14 days. Do not store above 25°C. If the carton needs to be removed permanently from refrigerator, the date of removal may be recorded on the outer carton. After removal from the refrigerator, Dupixent must be used within 14 days or discarded.
Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

Please contact Sanofi for products exposed to conditions other than described above. Refer to current BNF for company contact details.

 

See above
See above
12 October 2020
London MI Service

New Medicines

DupixentSevere atopic dermatitis in children aged ≥6 to 11 years who are inadequately controlled with topical therapies

Information

Dupixent
Licence extension / variation
Sanofi
Regeneron

Development and Regulatory status

Launched
Launched
Launched
November 2020
Nov 20Licence change to include use in children aged 6 to 11 years approved in EU [13].
Oct 20Recommended for EU approval by CHMP - the additional indication is "Children 6 to 11 years of age: Dupixent is indicated for the treatment of severe atopic dermatitis in children 6 to 11 years old who are candidates for systemic therapy" [12].
Aug 20Granted EAMS status by the MHRA for treatment of children aged 6 to 11 years with severe atopic dermatitis (allergic eczema) that is not controlled by medicines applied as creams or ointments to the skin [11].
May 20Approved in US [10].
Feb 20Has also been filed in the EU [9].
Jan 20The FDA has accepted for Priority Review the supplemental Biologics License Application for dupilumab as an add-on maintenance treatment for children aged 6 to 11 years with moderate-to-severe atopic dermatitis [8].
Nov 19Expected submission is now 2019 [7].
Mar 19Filings planned for 2019 [3].
Feb 19Filings will now be 2020 [5].
Oct 16FDA grants breakthrough therapy status for dupilumab for treatment of severe atopic dermatitis in children aged 6 months to less than 12 years of age, who are not adequately controlled with, or who are intolerant to, topical medication [4].

Category

Anti-interleukin-4 receptor (IL-4R) and anti-interleukin-13 receptor (IL-13R) human monoclonal antibody
Atopic eczema is common and the prevalence is increasing. Eczema affects 15-20% of school children and 2-10% of adults [1].
Severe atopic dermatitis in children aged ≥6 to 11 years who are inadequately controlled with topical therapies
Subcutaneous

Trial or other data

May 22NICE TA not selected. NICE will not progress with an appraisal for this indication due to positive guidance in the adult population within TA534 [14].
Aug 19Topline data for the PIII study found that 70% patients given dupilumab 300 mg every 4 weeks, and 67% given dupilumab 100 mg or 200 mg every 2 weeks achieved a 75% or greater skin improvement (EASI-75) vs 27% for placebo (p<0.0001 for both) [6].
Dec 17PIII trial to evaluate the efficacy of dupilumab in paediatric patients (6-11 year-olds) for the treatment of atopic dermatitis starts (NCT03345914). The trial is enrolling approximately 240 patients in the US. Primary outcome is proportion of patients with Investigator´s Global Assessment (IGA) 0 or 1 (on a 5-point scale) at week 16 Collection of these data is due to complete Jan 19 [2].

Evidence based evaluations

DupixentAdd-on maintenance treatment in children aged between 6 and 11 with moderate-to-severe asthma inadequately controlled with medium-to-high dose ICS plus another medicinal product

Information

Dupixent
Licence extension / variation
Sanofi
Regeneron

Development and Regulatory status

None
Launched
Launched
Apr 22Approved in EU for use in children aged 6 to 11 years as an add-on maintenance treatment for severe asthma with type 2 inflammation characterized by raised blood eosinophils and/or raised fractional exhaled nitric oxide (FeNO), who are inadequately controlled with medium to high dose inhaled corticosteroids (ICS) plus another medicinal product for maintenance treatment [13].
Jan 22CHMP recommends a change to the indications for Dupixant to permit use in children aged 6 to 11 years with severe asthma (previously only licensed from the age of 12). The proposed revised indication is “Dupixent is indicated in children 6 to 11 years old as add-on maintenance treatment for severe asthma with type 2 inflammation characterised by raised blood eosinophils and/or raised fraction of exhaled nitric oxide (FeNO) who are inadequately controlled with medium to high dose inhaled corticosteroids (ICS) plus another medicinal product for maintenance treatment” [11].
Oct 21Approved in US [8].
Apr 21Also filed in the EU. In US seeking an indication for 6 to 11-yr-olds with uncontrolled moderate to severe asthma, and in the EU seeking an indication for 6 to 11-yr-olds with uncontrolled severe asthma [7].
Feb 21FDA accepts sBLA for review [5].
Oct 20US and EU regulatory submissions for children aged 6-11 years planned by Q1 2021. [4]
Oct 19Filings will now be in 2021 [3].
Jul 18Filings planned for 2022 at the earliest [1].

Category

Anti-interleukin-4 receptor (IL-4R) and anti-interleukin-13 receptor (IL-13R) human monoclonal antibody
There were over 79,800 emergency hospital admissions for asthma in the UK in 2008/09. Of these, 30,740 were children aged 14 years or under. There were 1,131 deaths from asthma in the UK in 2009 (12 were children aged 14 years or under). An estimated 75% of admissions for asthma are avoidable and as many as 90% of the deaths from asthma are thought to be preventable.
Add-on maintenance treatment in children aged between 6 and 11 with moderate-to-severe asthma inadequately controlled with medium-to-high dose ICS plus another medicinal product
Subcutaneous

Trial or other data

Feb 22NICE decides not to add dupilumab for maintenance treatment of uncontrolled moderate to severe asthma in children 6 to 11 years to its work programme, as it is covered by the NHSE Commissioning Medicines for Children in Specialised Services Policy [12].
Dec 21PIII 52 week VOYAGE RCT (n=408), found those who received add-on dupilumab had fewer asthma exacerbations than those who received placebo (in patients with type 2 inflammatory phenotype, annualised rate was 0.31 vs. 0.75, respectively), as well as better lung function and asthma control [9].
May 21Manufacturers report positive results for PIII VOYAGE trial (n=408); dupilumab reduced date of severe asthma attacks vs placebo in children with asthma aged 6 to 11 years by between 65% and 59% over one year [6].
Oct 20Data from the PIII LIBERTY ASTHMA VOYAGE randomised, double-blind, placebo-controlled trial (n=408 children aged 6 to 12 years. Injection site reactions, viral upper respiratory tract infections and eosinophilia were most common adverse effects. [4]
Jun 18PIII Liberty Asthma Excursion trial to evaluate the long-term safety and tolerability of dupilumab SC in children, aged 7 to 12 years with asthma who completed the treatment in the Liberty Asthma Voyage trial starts (NCT03560466). The open-label, single group assignment trial will enrol approximately 236 patients in the US [2].
Mar 17PIII Liberty Asthma Voyage trial to assess the efficacy, safety and tolerability of dupilumab SC in children, aged 6 to 11 years, with uncontrolled persistent asthma starts (NCT02948959). The randomised trial will enrol 471 patients in the US and other countries including the EU (not UK). Primary outcome is annualised rate of severe exacerbation events during the placebo-controlled treatment period; collection of these data is due to complete Jul 21 [2].

Evidence based evaluations

DupixentSevere atopic dermatitis in children aged ≥6 months to 5 years who are inadequately controlled with topical therapies

Information

Dupixent
Licence extension / variation
Sanofi
Regeneron

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Jun 22FDA approves dupilimab for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable [10]
Feb 22US FDA accepts sBLA for priority review, and assigns a PDUFA action date of 9/6/22 [9].
Dec 21Results from the PIII LIBERTY AD PRESCHOOL trial will form the basis of global regulatory submissions for dupilumab in this age group, beginning with the US by the end of 2021 and the EU in H1 2022 [8].
Dec 20Filings still listed as 2022 in Sanofi pipeline [6].
Nov 19Filings still listed as 2022 in Sanofi pipeline [4].
Jul 18Filings will be 2022 or later [2].

Category

Anti-interleukin-4 receptor (IL-4R) and anti-interleukin-13 receptor (IL-13R) human monoclonal antibody
26 May 2020Atopic eczema is common and the prevalence is increasing. It is seen in 20% of children in developed countries and in developing countries the prevalence is heading towards this figure. The large majority (about 80%) of cases present before the age of 5 years [1].
Severe atopic dermatitis in children aged ≥6 months to 5 years who are inadequately controlled with topical therapies
Subcutaneous

Trial or other data

May 22NICE TA not selected. NICE will not progress with an appraisal for this indication due to positive guidance in the adult population within TA534 [11].
Dec 21Positive data from the PIII LIBERTY AD PRESCHOOL trial presented at the 2021 Revolutionizing Atopic Dermatitis Conference. At 16 weeks, patients who added dupilumab to low-potency topical corticosteroids (TCS) experienced the following, compared to TCS alone (placebo): 28% achieved clear or almost-clear skin vs 4% with placebo (p<0.0001), the primary endpoint; 53% achieved 75% or greater improvement in overall disease severity from baseline vs 11% with placebo (p<0.0001), the co-primary endpoint outside of the U.S; 49% average improvement from baseline in itch vs 2% improvement with placebo (p<0.0001); 70% average improvement from baseline in overall disease severity (EASI) vs 20% improvement with placebo (p<0.0001). The safety profile observed in the trial was consistent with the established safety profile of dupilumab in adults, adolescents and children 6 years and older with moderate-to-severe atopic dermatitis [8].
Aug 21LIBERTY AD PRESCHOOL trial meets all primary and secondary endpoints. Addition of dupilumab to topical corticosteroids was associated with higher achievement of clear or almost-clear skin (IGA score of 0 or 1; 28% v 4% placebo) and of ≥75% overall disease improvement (achieved by 53% v 11%, respectively) [7].
Dec 20Primary completion date for PII/III LIBERTY AD PRESCHOOL trial is now March 2022 [5].
Aug 18PII/III LIBERTY AD PRESCHOOL trial is recruiting [3].
Dec 17PII/III LIBERTY AD PRESCHOOL trial to evaluate the pharmacokinetics, safety and efficacy of dupilumab in patients aged ≥ 6 months to < 6 years with severe atopic dermatitis starts (NCT03346434). Part A of the study is designed to characterise safety and pharmacokinetics of a single dose of dupilumab. Part B is designed to demonstrate efficacy from multiple doses of dupilumab. The trial is enrolling approximately 280 patients in the US, Germany and UK. Collection of primary outcome data is due to complete Jan 22 [3].

DupixentEosinophilic oesophagitis in adults and adolescents

Information

Dupixent
Licence extension / variation
Sanofi
Regeneron

Development and Regulatory status

None
None
Launched
Yes
May 22FDA approves dupilumab 300 mg weekly to treat patients with eosinophilic esophagitis aged 12 years and older, weighing at least 40 kg [13]
Apr 22FDA accepts filing and grants priority review, with a decision expected 3 Aug. There is no medicine approved specifically for EoE in the US, where it affects 160,000 people, including 48,000 who have failed multiple treatments [12].
Feb 22Further data from the clinical trial program have been submitted to the U.S. FDA. Global regulatory filings in other countries are also planned in 2022 [11].
Nov 21Filed in US [10]
Sep 20US FDA grants Breakthrough Therapy Designation for eosinophilic esophagitis [7].
Apr 20Filings will now be 2022 [6].
Apr 19Filings now expected no earlier than 2023 [5].
Oct 18Filings planned for 2022 at the earliest [2].
Oct 17Granted orphan drug status in US [4].

Category

Anti-interleukin-4 receptor (IL-4R) and anti-interleukin-13 receptor (IL-13R) human monoclonal antibody
Eosinophilic esophagitis (EoE) is a chronic, allergic disease of the esophagus characterized clinically by symptoms of esophageal dysfunction (including vomiting, dysphagia, feeding disorders, food impaction and abdominal pain) which persist after treatment with proton pump inhibitors (PPIs). The current prevalence is estimated at 1/2,300-1/1,750 worldwide and appears to be on the increase. It is a predominantly male disorder [1].
Eosinophilic oesophagitis in adults and adolescents
Subcutaneous injection

Further information

Yes

Trial or other data

Feb 22Data from the second PIII trial presented at the 2022 American Academy of Allergy, Asthma and Immunology Annual Meeting showed that patients treated with dupilumab 300 mg weekly experienced the following changes by week 24 vs placebo: 64% reduction in disease symptoms from baseline vs 41% for placebo (p=0.0008); a 23.78 point improvement on the DSQ, vs 13.86 point improvement for placebo (p<0.0001); 59% of patients achieved histological disease remission vs 6% of patients receiving placebo (p<0.0001). Safety results of the trial were generally consistent with the known safety profile of dupilumab in its approved indications. The trial also found that significantly more patients treated with dupilumab 300 mg every 2 weeks reduced their esophageal eosinophilic count to the normal range compared to placebo; however there was not a significant improvement in dysphagia symptoms. Detailed results on the every 2 week dosing will be presented at an upcoming congress [11].
Oct 21Sanofi report positive results from second PIII trial (n=159). Dupilumab 300mg weekly significantly improved ability to swallow and reduced eosinophils (64% reduction in disease symptoms from baseline vs. 41% for placebo; p=0.0008) at 24 weeks, reinforcing positive results from first PIII trial. Regulatory filings planned for 2022 [9].
May 20 Results from Part A of the pivotal PIII trial (NCT03633617) announced by SANOFI. The trial met both of its co-primary endpoints, as well as all key secondary endpoints. By week 24, patients (n=81) treated with dupilumab 300 mg weekly experienced 69% reduction in disease symptoms vs 32% for placebo (p=0.0002); a 21.92 point improvement in disease symptoms (measured by the DSQ scale) with dupilumab vs a 9.60 point improvement for placebo (p=0.0004), and a 60% reduction in their eosophageal eosinophilic count to a normal range vs 5% for placebo (p<0.0001). The trial demonstrated similar safety results to the known safety profile of dupilumab in its approved indications. The trial is ongoing, with additional patients enrolling in Part B as well as patients continuing in a 28-week extended active treatment period (Part C) [8].
Sep 18PIII trial to evaluate the safety and efficacy of dupilumab treatment in adult and adolescent patients with eosinophilic oesophagitis starts (NCT03633617). 425 patients aged 12 years and older will be recruited in the US. Primary outcome measures are proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) at week 24, and absolute change in Dysphagia Symptom Questionnaire (DSQ) score from baseline to week 24. The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia. Collection of these data is due to complete Mar 22 [3].

Evidence based evaluations

DupixentPrurigo nodularis (PN) in adults

Information

Dupixent
Licence extension / variation
Sanofi Genzyme
Regeneron

Development and Regulatory status

None
Pre-registration (Filed)
Pre-registration (Filed)
May 22FDA accept sBLA for Priority Review with target action date 30 Sept 2022 [8]
Apr 22Sanofi and Regeneron file for approval in the US and EU [7].
Jan 22Filing planned for first half of 2022 [6].
Apr 20Filings planned for 2021 [3].

Category

Anti-interleukin-4 receptor (IL-4R) and anti-interleukin-13 receptor (IL-13R) human monoclonal antibody
The condition appears to be relatively common, particularly among patients who have some of the associated/precipitating conditions (infections, acute kidney injury, psychiatric conditions, malignancies); however, there are no surveys of its prevalence in the general population. It is more common in middle-aged women [1].
Prurigo nodularis (PN) in adults
Subcutaneous injection

Trial or other data

Jan 22Company announces results from a randomised double blind placebo-controlled multicentre parallel PIII study LIBERTY-PN PRIME in adults with uncontrolled prurigo nodularis (NCT04183335, n= 151). Primary outcome is improvement (reduction) in worst-itch numeric rating scale (WI-NRS) by ≥4 from baseline to week 24. 60% of pts on dupilumab met primary endpoint vs 18% with placebo at 24 weeks. 48% of pts on dupilumab vs 18% of placebo pts achieved clear or almost clear skin (p=0.0004). Dupilumab pts experienced greater improvements in quality of life, skin pain, symptoms of anxiety and depression. Company intends to file in first half of 2022. [6]
Oct 21PIII PRIME2 study meets all primary endpoints with 58% of patients treated with dupilumab experiencing a clinically meaningful reduction in itch at week 24 (v 20% on placebo) [5].
Dec 20PIII PRIME2 study is now due to complete July 2021 [4].
Jan 20PIII PRIME2 study to the efficacy of dupilumab on itch response in patients with prurigo nodularis (PN), inadequately controlled on topical prescription therapy or when those therapies are not advisable starts (NCT04202679). 150 adults will be recruited in the US, Canada and France. Primary outcome is improvement (reduction) in worst-itch numeric rating scale (WI-NRS) by ≥4 from baseline to week 12; collection of these data is due to complete Jan 21 [2].

Evidence based evaluations

DupixentModerate to severe chronic obstructive pulmonary disease (COPD) with type 2 inflammation

Information

Dupixent
Licence extension / variation
Sanofi Genzyme
Regeneron

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Human monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signalling. IL-4 and IL-13 are major drivers of human type 2 inflammatory disease [1,2]
In the UK, it is estimated that more than 3 million people currently have COPD, with the disease being undiagnosed in about 2 million of these. Most people are not diagnosed until they are ≥50 years old. Prevalence of COPD increases with age and varies significantly by region. A GP practice in the UK which cares for about 7000 people will have up to 200 people with COPD on its practice list . This equates to about 1.4 million consultations with GPs each year in the UK [3]
Moderate to severe chronic obstructive pulmonary disease (COPD) with type 2 inflammation
Subcutaneous injection

DupixentChronic spontaneous urticaria in patients who remain symptomatic despite the use of H1 antihistamines and who are naïve to, intolerant of, or incomplete responders to omalizumab

Information

Dupixent
Licence extension / variation
Sanofi Genzyme
Regeneron

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Anti-interleukin-4 receptor (IL-4R) and anti-interleukin-13 receptor (IL-13R) human monoclonal antibody
Approximately 15% of people experience urticaria at some time in their lives. Acute urticaria is much more common than chronic urticaria. (Estimated lifetime incidence is 1 in 6 people compared to 1 in 1,000.) The prevalence rate for chronic urticaria has been estimated as 1-5 per 1,000 [1].
Chronic spontaneous urticaria in patients who remain symptomatic despite the use of H1 antihistamines and who are naïve to, intolerant of, or incomplete responders to omalizumab
Subcutaneous injection

DupixentBullous pemphigoid

Information

Dupixent
Licence extension / variation
Sanofi Genzyme
Regeneron

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

Anti-interleukin-4 receptor (IL-4R) and anti-interleukin-13 receptor (IL-13R) human monoclonal antibody
The incidence of pemphigoid in the UK is estimated at 4.3 per 100,000 persons per year. In other parts of Europe the incidence is 0.7-1.3 per 100,000. It is the most commonly seen autoimmune blistering disease [1].
Bullous pemphigoid
Subcutaneous injection

Dupixent Chronic sinusitis without nasal polyps

Information

Dupixent
Licence extension / variation
Sanofi Genzyme
Regeneron

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

An anti-interleukin-4 receptor (IL-4R) and anti-interleukin-13 receptor (IL-13R) human monoclonal antibody
Chronic sinusitis is a common condition, affecting 1 in 10 UK adults. Data suggest a prevalence of 4.5-12% in North American and European populations. Its prevalence increases with age, and it is more likely to occur in women, and in people with asthma, chronic obstructive pulmonary disease, or a history of allergy [1].
Chronic sinusitis without nasal polyps
Subcutaneous injection

DupixentPrimary acquired chronic inducible cold urticaria (ColdU) in patients aged 12 years and older

Information

Dupixent
Licence extension / variation
Sanofi
Regeneron

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signalling by specifically binding to the IL-4Rα subunit shared by the IL-4 and IL-13 receptor complexes
Acquired cold urticaria is rare and the exact number of people that have it is unknown. The incidence in central Europe is thought to be 0.05%. It usually affects young adults, but can appear at any age. It is twice as common in females than males. Cold urticaria usually lasts for some years. About 30% report resolution of symptoms within 5 to 10 years. A 20-year follow-up study of 41 patients diagnosed with cold urticaria showed it had resolved by 10 years in about a quarter of patients [2,3].
Primary acquired chronic inducible cold urticaria (ColdU) in patients aged 12 years and older
Subcutaneous injection

Evidence based evaluations