FDA Approves Brepocitinib to Treat Dermatomyositis Save

Dermatomyositis is a rare autoimmune disease, that affects roughly 40,000–45,000 people in the USA. This rare, devastating, autoimmune condition where the standards of care in DM (glucocorticoids, methotrexate, csDMARDs) are historic and unproven, leaving a large unmet therapeutic need. In 2021 the FDA approved intravenous immunoglobulin (Octagam), and now we have an brepocitinib - an oral, once daily addition to this short list of approved therapies.

The efficacy and safety of brepocitinib was demonstrated in the VALOR study - a phase 3 randomized, double-blind, multicenter, placebo-controlled study that enrolled 241 DM who were randomized to either brepocitinib 30 mg once daily, brepocitinib 15 mg once daily or placebo for a 52-weeks. The main outcome was the Total Improvement Score (TIS) at week 52.  Participants treated with Lisraya 30 mg had a higher average TIS score (indicating greater clinical response and disease control) and better skin outcome scores at week 52 compared to those who received a placebo. Moreover, they also showed improvements in physical function and less reliance onf corticosteroid use.

Some of the most common adverse reactions to Lisraya were upper respiratory tract infection, headache, fatigue, urinary tract infection, and nausea.

Lisraya carries the same boxed warning as all other JAK inhibitors, indicating a potential increased risk for serious infections, increased all-cause mortality (a higher risk of death from any cause), malignancies (cancers), major adverse cardiovascular events (serious heart and blood vessel problems), and thrombosis (blood clots).

Other notes from the product label: 

• LISRAYA is not recommended for use in combination with other JAK inhibitors, other TYK2 inhibitors, or biologic DMARDs
• Prior to treatment patients should be tested for latent tuberculosis (TB) infection, viral hepatitis screening, a complete blood count, baseline hepatic and renal function tests, verifying pregnancy status, and updating immunizations.
• The drug should b avoided in those with active hepatitis B or hepatitis C, an absolute lymphocyte count less than 500 cells/mm3 , absolute neutrophil count less than 1,000 cells/mm3 , or hemoglobin level less than 8 g/dL. (2.1)
• The recommended dosage is 30 mg once daily, administered orally with or without food.
• Warnings for:GI perforations; Hypoglycemia in Patients with Diabetes; Laboratory Abnormalities (suggested monitoring for lymphocyte counts, neutrophil counts, hemoglobin, liver enzymes, including GGT, and lipids); avoid using with live vaccines.
• Embryofetal Toxicity: Based on animal studies, LISRAYA may cause fetal harm. Advise female patients of reproductive potential of the potential risk to a fetus and to use effective contraception.
• Lisray is not recommended in patients with severe renal impairment or those with severe hepatic impairment.
• Herpes virus reactivation (e.g., herpes zoster) has been reported.
• Brepocitinib mean terminal half-life ranged from 5.4 to 12 hours

The FDA granted Lisraya Orphan Drug and Priority Review designations.