Fall Clinical Dermatology 2020: Lilly and Incyte Showcase Positive New Data for Baricitinib in Adult Patients with Alopecia Areata
Data from the Phase 2 portion of BRAVE-AA1, an ongoing Phase 2/3 study evaluating the safety and efficacy of baricitinib in adult patients with AA will be shared. The study included adult patients with a current episode of AA lasting for 6 months to 8 years with a Severity of Alopecia Tool (SALT) score ≥50 (i.e. who had ≥50% scalp hair loss) and no spontaneous improvement over six months prior to screening. In the Phase 2 portion, patients were randomized to oral baricitinib 1-mg, 2-mg, 4-mg or placebo once daily, in order to identify up to two doses for the Phase 3 portion. Interim analyses were conducted after patients completed 12 and 36 weeks of treatment, the latter for the primary endpoint of the Phase 2 part of the study. At Week 36, the proportion of patients achieving the primary endpoint of SALT ≤20 defined as having 20% or less of scalp hair loss and considered as clinically meaningful improvement, was significantly greater in baricitinib 2-mg (33.3%, p=0.016), and 4-mg (51.9%, p=0.001) groups compared to placebo (3.6%). Based on the interim results of the Phase 2 part of the study, the Phase 3 portion of BRAVE-AA1 and an additional Phase 3 trial (BRAVE-AA2) were initiated and are ongoing to assess the efficacy and safety of the 2-mg and 4-mg doses of baricitinib relative to placebo.
"Alopecia areata is a challenging disease that currently has no FDA-approved treatment options, making it difficult for healthcare providers to best serve the needs of these patients," said
The proportion of adult patients achieving no hair loss or limited hair loss on the patient-reported outcomes (PRO) for scalp hair assessment were significantly greater in the 2-mg and 4-mg groups compared to placebo (p<0.05) by Week 36. Similarly, patients receiving the 4-mg dose of baricitinib improved growth of eyebrows and eyelashes as assessed by the clinician-reported outcome and PRO measures (p<0.05 versus placebo). In the Phase 2 portion, the most common adverse event was upper respiratory tract infection which occurred in 17.9%, 11.1% and 22.2% of patients in placebo, 2-mg and 4-mg groups, respectively. No serious adverse events, deaths, thrombotic events or new safety concerns were reported.
"Patients with alopecia areata deal with unpredictable and long-lasting episodes of hair loss and many don't find relief from the therapies that are currently used," said Lotus Mallbris, M.D., Ph.D., vice president of immunology development at
"Alopecia areata carries a considerable emotional burden for people living with the disease, affecting their quality of life and wellbeing, social interactions and ability to live a normal life," said
In March, the FDA granted Breakthrough Therapy designation to baricitinib for the treatment of AA based on positive Phase 2 results from BRAVE-AA1. Breakthrough Therapy designation aims to expedite the development and review of drugs where preliminary data indicates they may demonstrate substantial improvement over already available therapies.
For more information about the
Baricitinib, an oral JAK1/JAK2 inhibitor discovered by
Indication and Usage for OLUMIANT (baricitinib) tablets (in the
OLUMIANT® (baricitinib) 2-mg is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Limitation of Use: Not recommended for use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine.
IMPORTANT SAFETY INFORMATION FOR OLUMIANT (baricitinib) TABLETS
WARNING: SERIOUS INFECTIONS, MALIGNANCY, AND THROMBOSIS
SERIOUS INFECTIONS: Patients treated with Olumiant are at risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt Olumiant until the infection is controlled. Reported infections include:
- Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease. Test patients for latent TB before initiating Olumiant and during therapy. If positive, start treatment for latent infection prior to Olumiant use.
- Invasive fungal infections, including candidiasis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
- Bacterial, viral, and other infections due to opportunistic pathogens.
Carefully consider the risks and benefits of Olumiant prior to initiating therapy in patients with chronic or recurrent infection.
Closely monitor patients for the development of signs and symptoms of infection during and after treatment with Olumiant including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
MALIGNANCIES: Lymphoma and other malignancies have been observed in patients treated with Olumiant.
THROMBOSIS: Thrombosis, including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been observed at an increased incidence in patients treated with Olumiant compared to placebo. In addition, there were cases of arterial thrombosis. Many of these adverse events were serious and some resulted in death. Patients with symptoms of thrombosis should be promptly evaluated.
WARNINGS AND PRECAUTIONS
SERIOUS INFECTIONS: The most common serious infections reported with Olumiant included pneumonia, herpes zoster and urinary tract infection. Among opportunistic infections, tuberculosis, multidermatomal herpes zoster, esophageal candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis, cytomegalovirus and BK virus were reported with Olumiant. Some patients have presented with disseminated rather than local disease and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids. Avoid Olumiant in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating Olumiant in patients:
- with chronic or recurrent infection
- who have been exposed to TB
- with a history of a serious or an opportunistic infection
- who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or
- with underlying conditions that may predispose them to infection.
Closely monitor patients for infections during and after Olumiant treatment. Interrupt Olumiant if a patient develops a serious infection, an opportunistic infection, or sepsis. Do not resume Olumiant until the infection is controlled.
Tuberculosis – Before initiating Olumiant evaluate and test patients for latent or active infection and treat patients with latent TB with standard antimycobacterial therapy. Olumiant should not be given to patients with active TB. Consider anti-TB therapy prior to initiating Olumiant in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection. Monitor patients for TB during Olumiant treatment.
Viral Reactivation – Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies with Olumiant. If a patient develops herpes zoster, interrupt Olumiant treatment until the episode resolves.
The impact of Olumiant on chronic viral hepatitis reactivation is unknown. Screen for viral hepatitis in accordance with clinical guidelines before initiating Olumiant.
MALIGNANCY AND LYMPHOPROLIFERATIVE DISORDERS: Malignancies were observed in Olumiant clinical studies. Consider the risks and benefits of Olumiant prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing Olumiant in patients who develop a malignancy. NMSCs were reported in patients treated with Olumiant. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.
THROMBOSIS: Thrombosis, including DVT and PE, has been observed at an increased incidence in Olumiant-treated patients compared to placebo. In addition, arterial thrombosis events in the extremities have been reported in clinical studies with Olumiant. Many of these adverse events were serious and some resulted in death. There was no clear relationship between platelet count elevations and thrombotic events. Use Olumiant with caution in patients who may be at increased risk of thrombosis. If clinical features of DVT/PE or arterial thrombosis occur, evaluate patients promptly and treat appropriately.
GASTROINTESTINAL PERFORATIONS: Gastrointestinal perforations have been reported in Olumiant clinical studies, although the role of JAK inhibition in these events is not known. Use Olumiant with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis). Promptly evaluate patients who present with new onset abdominal symptoms for early identification of gastrointestinal perforation.
Neutropenia – Olumiant treatment was associated with an increased incidence of neutropenia (absolute neutrophil count [ANC] <1000 cells/mm3) compared to placebo. Avoid initiation or interrupt Olumiant treatment in patients with an ANC <1000 cells/mm3. Evaluate at baseline and thereafter according to routine patient management.
Lymphopenia – Absolute lymphocyte count (ALC) <500 cells/mm3 were reported in Olumiant clinical trials. Lymphocyte counts less than the lower limit of normal were associated with infection in patients treated with Olumiant, but not placebo. Avoid initiation or interrupt Olumiant treatment in patients with an ALC <500 cells/mm3. Evaluate at baseline and thereafter according to routine patient management.
Anemia – Decreases in hemoglobin levels to <8 g/dL were reported in Olumiant clinical trials. Avoid initiation or interrupt Olumiant treatment in patients with hemoglobin <8 g/dL. Evaluate at baseline and thereafter according to routine patient management.
Liver Enzyme Elevations – Olumiant treatment was associated with increased incidence of liver enzyme elevation compared to placebo. Increases of ALT ≥5x upper limit of normal (ULN) and increases of AST ≥10x ULN were observed in patients in Olumiant clinical trials.
Evaluate at baseline and thereafter according to routine patient management. Promptly investigate the cause of liver enzyme elevation to identify potential cases of drug-induced liver injury. If increases in ALT or AST are observed and drug-induced liver injury is suspected, interrupt Olumiant until this diagnosis is excluded.
Lipid Elevations – Treatment with Olumiant was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Assess lipid parameters approximately 12 weeks following Olumiant initiation. Manage patients according to clinical guidelines for the management of hyperlipidemia.
VACCINATIONS: Avoid use of live vaccines with Olumiant. Update immunizations in agreement with current immunization guidelines prior to initiating Olumiant therapy.
HYPERSENSITIVITY: Reactions such as angioedema, urticaria, and rash that may reflect drug sensitivity have been observed in patients receiving Olumiant, including serious reactions. If a serious hypersensitivity reaction occurs, promptly discontinue Olumiant while evaluating the potential causes of the reaction.
Most common adverse reactions include: upper respiratory tract infections (16.3%, 11.7%), nausea (2.7%, 1.6%), herpes simplex (0.8%, 0.7%) and herpes zoster (1.0%, 0.4%) for Olumiant 2 mg and placebo, respectively.
USE IN SPECIFIC POPULATIONS
PREGNANCY AND LACTATION: No information is available to support the use of Olumiant in pregnancy or lactation. Advise women not to breastfeed during treatment with Olumiant.
HEPATIC AND RENAL IMPAIRMENT: Olumiant is not recommended in patients with severe hepatic impairment or in patients with severe renal impairment.
BA HCP ISI 09JUL2020
OLUMIANT is a once-daily, oral JAK inhibitor approved in the
About Alopecia Areata
Alopecia areata (AA) is a common autoimmune skin disease which results in hair loss on the scalp, face and sometimes other areas of the body. AA often first appears during childhood and can be different for everyone who has it. People of all ages, males/females and all ethnic groups can develop AA.
By following the science through unchartered territory, we continue
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about OLUMIANT (baricitinib) as a treatment for patients with moderate to severe atopic dermatitis and reflects
1 Olumiant Prescribing Information, 2020.
2 Walker JG and Smith MD. J Rheumatol. 2005;32;1650-1653.
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