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34345911000001107

New Medicines

OlumiantModerate to severe atopic dermatitis in adults

Information

Olumiant
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

Launched
Launched
Pre-registration (filed)
October 2020
Apr 21US FDA has extended review period for baricitinib for moderate-to-severe AD. This is to provide more time to review new data analyses submitted by Lilly, per requests made by the FDA. Decision is now expected early Q3 2021 [18]
Oct 20Licence extension approved in EU [17].
Sep 20Recommended for EU approval by CHMP - the additional indication is "for the treatment of moderate to severe atopic dermatitis in adult patients who are candidates for systemic therapy" [15].
Jan 20Has been filed in the EU, with CHMP decision expected May 20 [13,14].
Jan 18PIII development starts [3].
Sep 17Eli Lilly plans to start PIII trials by end of 2017 [1].

Category

Selective JAK1 and JAK2 inhibitor; JAK3-sparing.
Atopic 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.[1]In adults, population studies report an overall prevalence of 2-18%. The large majority (about 80%) of cases present before the age of 5 years [2].
Moderate to severe atopic dermatitis in adults
Oral

Further information

Yes

Trial or other data

Oct 20PIII BREEZE-AD7 RCT (n=329) found dose of 4mg baricitinib in combination with background topical corticosteroids significantly improved signs and symptoms of moderate to severe atopic dermatitis at week 16 (IGA score clear/almost clear in 31%, 24% and 15% on 4mg, 2mg and placebo, respectively) [16].
Feb 20Topline results from BREEZE-AD5 study (n=440) are announced. In this study, the 2-mg dose of baricitinib met the primary endpoint as defined by the proportion of participants achieving EASI75 at Week 16 (29.5% vs. 8.2% placebo; p<0.001) [12].
Jan 20In BREEZE-AD4, the primary endpoint of proportion of patients achieving at least a 75% or better change from baseline in the Eczema Area and Severity Index (EASI) at Week 16 was achieved in patients treated with baricitinib 4mg plus corticosteroids [11].
Aug 19Lilly announces baricitinib, in combination with topical corticosteroids in adults with mod to severe AD, met primary end points in PIII BREEZE-AD7 study. Primary end points included a 4-point improvement in Itch NRS at Week 16. The EASI-75 scores (improvement of ≥75% in Eczema Area and Severity Index score from baseline) at Week 16, were acheived by 23%, 43% and 48% of pts on placebo, baricitinib 2mg and 4mg respectively (p<0.01 and 0.001 respectively). Safety data remained consistent with no major adverse cardiovascular events, or deaths reported. However, one pulmonary embolism was reported in the baricitinib gp. [8-10]
Feb 19Baricitinib met the primary endpoint in PIII BREEZE-AD1 and BREEZE-AD2 trials evaluating it as a monotherapy vs. placebo in pts with moderate to severe atopic dermatitis. A statistically significant proportion of pts achieved the primary endpoint (Investigator´s Global Assessment for AD (IGA) score of clear or almost clear (IGA 0,1) skin) at Week 16 vs. placebo. In both trials, the incidence of treatment-emergent adverse events (TEAE) and serious adverse events with baricitinib was similar to placebo. The most common TEAE´s were nasopharyngitis and headache. No VTEs, major adverse cardiovascular events (MACE), or deaths were reported. Full data will be shared at future conferences and in peer-reviewed journals.[7]
Sep 18PIII trial (n=300) assessing the efficacy and safety of baricitinib in combination with topical corticosteroids in adults with moderate-to-severe atopic dermatitis (EudraCT2018-001726-26) starts. The primary endpoint is the proportion of patients achieving IGA of 0 or 1 with a ≥2 point improvement [6].
Jun 18Recruitment to PIII BREEZE-AD6 trial (NCT03559270) to evaluate long-term efficacy and safety of baricitinib in adult patients who have completed participation in BREEZE-AD5 to start 27/06/18 [5].
Feb 18PIII BREEZE-AD5 trial to evaluate efficacy and safety of baricitinib in adult patients with moderate to severe atopic dermatitis starts recruiting (NCT03435081). Proportion of participants achieving the investigator´s global assessment (IGA) of 0 or 1 with a ≥ 2 point improvement in a time frame of 16 weeks will be the primary endpoint evaluated in the trial. 450 patients will be recuirted in the US, Canada and Puerto Rico. Collection of primary outcome data is due to complete Dec 18 [4].
Sep 17In a PII trial, baricitinib hit its primary endpoint but missed a secondary objective. The oral JAK inhibitor was compared to placebo alongside topical steroid treatment in patients with moderate to severe atopic dermatitis. At the highest dose tested (4 mg), 61% of patients on baricitinib had at least a 50% reduction in symptoms (EASI-50), compared to 37% of the steroid plus placebo group. The lower 2 mg dose arm failed to show a significant difference from the control group, and on another secondary endpoint—a 75% improvement in symptoms or EASI-75—neither dose outperformed control. Analysts at Jefferies said that the data do not match the results seen in phase 2a with Dupixent (dupilumab) injections plus steroids, and suggest much of the effect with baricitinib is seen in more severely affected patients [1].

Evidence based evaluations

OlumiantCoronavirus disease 2019 (COVID-19) in hospitalised patients, to prevent inflammatory cascade

Information

Olumiant
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

None
Pre-registration (Filed)
Pre-registration (Filed)
Jul 21 US FDA expands EUA for baricitinib to include treatment with or without remdesivir, based on data from the COV-BARRIER study. Baricitinib can now be used to treat adults and paediatrics aged ≥2 who need supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO [10].
Jun 21The EMA has identified five "most promising" COVID-19 therapeutics already in an advanced stage of development that it will prioritise, with the aim of providing more regulatory flexibility with rolling reviews, conditional marketing authorisations and flexible labelling and packaging requirements. At least three of these new products will be authorised by Oct 2021. Baricitinib is one of the 5 products [9].
Apr 21EMA are evaluating an application to extend use of baricitinib to include hospitalised COVID-19 patients aged ≥10 years requiring supplemental oxygen. A decision is expected July 2021 [8].
Nov 20US FDA, as part of its Coronavirus Treatment Acceleration Programme (CTAP), issues an emergency use authorisation (EUA) for the usage of baricitinib, to be administered as a combination therapy with remdesivir. Baricitinib is authorised for use for the treatment of suspected or laboratory confirmed coronavirus disease 2019 (COVID-2019) infections, in hospitalised adults and pediatric patients, aged two years or older requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. The recommended dose for this EUA is baricitinib 4 mg once daily for 14 days or until hospital discharge. The EUA decision was based on data from the ACTT-2 trial [6].
Oct 20Eli Lilly and Incyte Corporation submit an initial request to the FDA for EUA, based on favourable data displaying that the combination therapy reduced time to recovery and improved clinical outcomes for patients with COVID-19 infections compared with remdesivir [6].
Apr 20Baricitinib to be investigated in NIAID trial [1].

Category

JAK1/JAK2 inhibitor
COVID-19 is an infectious disease caused by a newly discovered coronavirus. Most people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without requiring special treatment. Older people, and those with underlying medical problems are more likely to develop serious illness [2].
Coronavirus disease 2019 (COVID-19) in hospitalised patients, to prevent inflammatory cascade
Oral

Trial or other data

Aug 21Topline data announced from an extra cohort of 101 adults from the COV-BARRIER sub-study. Pts on mechanical ventilation or receiving ECMO who were dosed with baricitinib + standard of care treatment were 46% less likely to die by day 28 vs. standard of care + placebo. [11]
Apr 21Company announces PIII COV-BARRIER study of baricitinib + standard of care (SoC) vs placebo + SoC failed to meet statistical significance against COVID-19 for its primary endpoint (proportion of pts progressing to the first reporting of non-invasive ventilation or death by Day 28). Pts on baricitinib were 2.7% less likely than pts on SoC to progress to ventilation. The number of adverse events and serious adverse events were similar in the baricitinib (44.5% and 14.7%), vs placebo (44.4% and 18.0%). In the baricitinib group, 8.5% had serious infectious and 2.7% had venous thromboembolism vs 9.8% and 2.5% in placebo group [7]
Dec 20PIII NCT04401579 (n=1033) found baricitinib+remdesivir was superior to remdesivir in reducing recovery time (median time to recovery 7 vs 8 days; rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P=0.03) with clinical improvement in those receiving high-flow oxygen (1.51; 1.10 to 1.6) [5].
Sep 20Baricitinib in combination with remdesivir reduces time to recovery in hospitalised patients with COVID-19 in NIAID-sponsored ACTT-2 trial. Lilly plans to discuss potential for emergency use authorisation with FDA and with other regulatory agencies [4].
Jun 20First patient enrolled in COV-BARRIER PIII randomised, double-blind, placebo–controlled study (NCT04421027; EudraCT2020-001517-21) to evaluate the efficacy and safety of baricitinib, an oral JAK1/JAK2 inhibitor licensed from Incyte, in hospitalised adults with COVID-19 [3].
Apr 20Baricitinib to be an arm in NIAID´s Adaptive COVID-19 Treatment Trial. The study will investigate the efficacy and safety of baricitinib as a potential treatment for hospitalized patients diagnosed with COVID-19, beginning this month in the U.S. with a planned expansion to additional sites including Europe and Asia. Results are expected within the next two months [1].

OlumiantSystemic lupus erythematosus (SLE) in adults

Information

Olumiant
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Selective JAK1 and JAK2 inhibitor; JAK3-sparing.
Age-standardised SLE incidence in the UK during the 1990s was 7.89 per 100,000 for females and 1.53 per 100,000 for males, with an overall female-to-male ratio of 5.2:1. Peak incidence occurred at age 50-54 years for females and 70-74 years for males. It is more common in those of Chinese, Southeast Asian (1 in 1,000) and Afro-Caribbean origin (1 in 500) [3].
Systemic lupus erythematosus (SLE) in adults
Oral

Further information

Yes

Evidence based evaluations

Olumiant Moderate to severe atopic dermatitis in children aged 2-17 years

Information

Olumiant
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
None

Category

Selective JAK1 and JAK2 inhibitor; JAK3-sparing.
Atopic 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].
Moderate to severe atopic dermatitis in children aged 2-17 years
Oral

OlumiantSevere alopecia areata in adults

Information

Olumiant
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

None
None
Pre-registration (Filed)
Jul 21Has been filed for approval, presumably to the FDA [5].
Apr 21Lilly plans to submit a supplemental New Drug Application (sNDA) to the FDA for baricitinib in alopecia in H2 2021, followed by submissions to other regulatory agencies around the world [4].
Mar 20Granted Breakthrough Therapy designation for the treatment of alopecia areata based on the results from the BRAVE-AA1 study.[3]

Category

Selective JAK1 and JAK2 inhibitor; JAK3-sparing. Dose is 2mg to 4mg once daily.
Alopecia areata is a chronic inflammatory disease, which affects hair follicles and sometimes nails. Estimated prevalence in the UK is 15 per 10,000 of the population. It can affect any age but onset is most common in childhood and adolescence. Incidence peaks between the ages of 15 and 29. 50-60% develop a first bald patch before the age of 21. Males and females are affected equally. There is nail involvement in 10-15% [1].
Severe alopecia areata in adults
Oral

Trial or other data

Apr 21Further results have been announced: In BRAVE-AA1, at week 36, proportion of patients reaching at least 80% scalp hair coverage was achieved by 35% (p≤0.001) of patients on baricitinib 4mg/day and 22% (p≤0.001) of patients on baricitinib 2mg/day vs. 5% on placebo. In BRAVE-AA2, at week 36, proportion of patients reaching at least 80% scalp hair coverage was achieved by 33% (p≤0.001) on 4mg/day and 17% (p≤0.001) on 2mg/day vs. 3% on placebo [4].
Mar 21Topline data from the BRAVE-AA2 study in 546 adults showed 2mg and 4mg doses regrew hair in in pts with >50% scalp hair loss (and an episode lasting 6months to 8 years) vs. placebo at 36 weeks. The companies report this improvement was statistically significant for both doses. The safety profile was consistent with that in pts using it for rheumatoid arthritis and atopic dermatitis with no deaths, major adverse cardiovascular events, or venous thromboembolic events.[3]
Feb 21PIII BRAVE-AA2 study has also finished recruiting and completed collection of primary outcome data in the previous month [2].
Jan 21PII/III BRAVE-AA1 study is no longer recruiting [2].
Jul 19PIII BRAVE-AA2 study (NCT03899259) to assess if baricitinib is safe and effective in adults with severe or very severe alopecia areata starts. 725 adults will be recruited in the US, Japan, South Korea, Mexico and Puerto Rico plus additional countries (none UK or in Europe). Primary outcome is percentage of participants achieving severity of alopecia tool (SALT) ≤20 at week 36; collection of these data is due to complete Jan 21 [2].
Sep 18PII/III BRAVE-AA1 study designed to select up to two doses of baricitinib (referred to as low dose and high dose) and assess their efficacy and safety for the treatment of severe or very severe alopecia areata starts (NCT03570749). 725 adults will be recruited in the US, Japan, South Korea, Mexico and Puerto Rico. Primary outcome is percentage of Participants Achieving Severity of Alopecia Tool (SALT) ≤20 at week 36; collection of these data is due to complete Feb 21 [2].

Olumiant Juvenile idiopathic arthritis in children aged 1 to 17 years - second-line

Information

Olumiant
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

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

Category

Selective JAK1 and JAK2 inhibitor; JAK3-sparing.
The overall prevalence is estimated to be 1-2 per 1,000 children, with an incidence of 1 per 10,000. It is more common in females, although there are differences depending on the subset. It is described in all geographical areas but with large variations [1].
Juvenile idiopathic arthritis in children aged 1 to 17 years - second-line
Oral