Lebrikizumab

Lebrikizumab plus topical steroids safe, effective in atopic dermatitis treatment

Posted by

0


Combination lebrikizumab and topical corticosteroids outperformed topical corticosteroids alone in the treatment of atopic dermatitis in adolescents and adults, according to a phase 3 study.

“Currently, emollients and topical corticosteroids (TCS) are mainstay treatments for mild AD. In moderate to severe AD, the addition of systemic therapy and/or phototherapy is recommended,” Eric L. Simpson, MD, MCR, Frances J. Storrs Medical Dermatology Professor at Oregon Health and Science University and principal investigator of the ADhere trial, and colleagues wrote. “Due to the heterogeneity of AD, there remains a need to provide additional therapeutic options for long-term management.”

Dermatitis itch 3
Combination lebrikizumab and topical corticosteroids outperformed topical corticosteroids alone in the treatment of atopic dermatitis in adolescents and adults.

The 16-week, double-blind, placebo-controlled, multicenter, phase 3 ADhere trial analyzed the efficacy and safety of lebrikizumab, a novel monoclonal antibody that targets and neutralizes interleukin-13 signaling, in combination with low- to mid-potency TCS for the treatment of AD in adolescents and adults. These results, published in JAMA Dermatology, follow an Eli Lilly press release from April 2022.

In the study, a total of 211 patients (median age, 37.2 years; 48.8% female) were randomly assigned to receive 500 mg of subcutaneous lebrikizumab at baseline and week 2 followed by 250 mg every 2 weeks plus TCS or placebo plus TCS for 16 weeks.

By week 16, results showed 41.2% of lebrikizumab plus TCS-treated patients achieved the primary endpoint of a 0 or 1 IGA score compared with 22.1% of the placebo group (P = .01). Additionally, 69.5% of patients treated with lebrikizumab plus TCS achieved the key secondary endpoint of EASI 75 compared with 42.2% of the placebo group (P < .001).

Safety data demonstrated findings consistent with previously reported AD trials. Most treatment-related adverse events were not considered serious and were mild or moderate in severity, according to the study, and included conjunctivitis, headache, hypertension, injection site reactions and herpes infection. Serious adverse events were reported by two patients in the lebrikizumab plus TCS group and one patient in the placebo group.

“Treatment with [lebrikizumab plus TCS vs. placebo plus TCS] achieved statistically significant improvements in the signs and symptoms of moderate to severe AD in adolescents and adults,” Simpson and colleagues wrote. “The [lebrikizumab plus TCS] group had a benefit to risk profile consistent with prior lebrikizumab AD studies. Taken together, the efficacy and safety data reported herein suggest that [lebrikizumab plus TCS] may be an effective treatment option for adult and adolescent patients with moderate to severe AD.”

Lebrikizumab effective against moderate-to-severe atopic dermatitis, trials find

Posted by

0


Key takeaways:

  • The whole monoclonal antibody lebrikizumab was effective in a pair of trials against atopic dermatitis in children and adults.
  • The goal is FDA approval by the end of 2023.

Two phase 3 trials found that lebrikizumab was effective against moderate-to-severe atopic dermatitis in adolescents and adults, researchers reported in The New England Journal of Medicine.

“Lebrikizumab is a whole monoclonal antibody that targets interleukin-13, which has been shown to be important in the pathogenesis of atopic dermatitis,” Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research and an associate professor of dermatology at the George Washington University School of Medicine and Health Sciences, told Healio.

IDC0323Silverberg_Graphic_01_WEB

Silverberg and colleagues conducted a pair of randomized, double-blind, placebo-controlled phase 3 trials of lebrikizumab administered subcutaneously every 2 weeks to adolescents aged 12 to 17 years and adults aged 18 year or older with moderate-to-severe atopic dermatitis.

Both trials included a 16-week induction period and a 36-week maintenance period. The results reported in the journal included outcomes only for the 16-week induction period.

The researchers randomly assigned participants in a 2:1 ratio to receive a 250 mg dose of either lebrikizumab or a placebo, administered under the skin every 2 weeks throughout the induction period, with a loading dose of 500 mg given at baseline and week 2.

Silverberg and colleagues measured outcomes using an Investigator’s Global Assessment score ranging from 0 to 4. The primary outcome was a score of 0 or 1 — which indicates “clear or almost clear skin,” they wrote — with a score reduction of at least 2 points from baseline at week 16, which they noted would indicate an improvement.

In the first trial, 43.1% of 283 subjects in the lebrikizumab group met the primary outcome compared with 12.7% of 141 patients in the control group, the researchers reported. In the second trial, 33.2% of 281 patients in the lebrikizumab group met the primary outcome vs. 10.8% of 146 patients in the control group.

“There were many, many outcome measures that were assessed, and it almost didn’t matter. All of them showed great improvement with lebrikizumab treatment,” Silverberg said. “We were certainly very optimistic already based on the last few studies, and quite fortunately, the results have delivered, I think, as well or even better than anyone expected.”

“When we see this kind of reproducible high level of efficacy with a collective interleukin-13 blocker, and compare that with other therapies that are out there, it indicates that this mechanism, indeed, is highly effective and is sufficient, essentially to achieve good results,” Silverberg said.

He said they are “optimistic” that lebrikizumab will be authorized by the end of the year.

“Our hope is that the FDA will approve lebrikizumab before the end of 2023,” Silverberg said.

Lebrikizumab shows promise in adolescents with uncontrolled asthma

Posted by

0


Lebrikizumab reduced exacerbations in adolescents with uncontrolled asthma and had a favorable safety profile, according to results of the ACOUSTICS study.

The study, which was stopped early by the sponsor, showed a greater treatment effect with the higher dose of lebrikizumab studied.

Doctor female patient teen_Adobe Stock_188725706

Stanley J. Szefler, MD, researcher in the department of pediatrics at the Children’s Hospital Colorado and University of Colorado School of Medicine, reported results from the phase 3, multicenter, randomized, double-blind, placebo-controlled ACOUSTICS study at the American Thoracic Society International Conference. The trial aimed to evaluate efficacy, safety and tolerability of lebrikizumab (Eli Lilly).

The study enrolled 346 adolescents aged 12 to 17 years with uncontrolled asthma despite daily use of an inhaled corticosteroids and at least one other controller medication. Those enrolled also had a prebronchodilator FEV1 of 40% to 90% predicted, a bronchodilator response of 12% or more and were on stable background therapy. Patients were randomly assigned to receive lebrikizumab 125 mg (n = 75) or 37.5 mg (n = 58) or placebo (n = 91) subcutaneously once every 4 weeks. The trial was designed to be a 52-week study. Szefler presented results from 224 (65%) of adolescents who completed the 52-week placebo-controlled period.

The primary outcome was asthma exacerbation rate during the study period. Researchers also assessed time to first asthma exacerbation and safety outcomes.

At baseline, median blood eosinophil count was 295 cells/µL. Compared with the placebo group, patients assigned lebrikizumab 125 mg had a 51% (adjusted RR = 0.49; 95% CI, 0.28-0.83) reduction in exacerbation rates and those assigned 37.5 mg had a 40% (aRR = 0.6; 95% CI, 0.35-1.03) reduction, according to the data presented.

The reduction in asthma exacerbation rates with lebrikizumab compared with placebo was greatest in those with baseline blood eosinophil counts of 300 cells/µL or more. In those with blood eosinophil counts of 300 cells/µL or more, the lebrikizumab 125 mg group had a 56% (RR = 0.44; 95% CI, 0.21-0.89) reduction in asthma exacerbation rates and those assigned 37.5 mg had a 58% (RR = 0.42; 95% CI, 0.19-0.93) reduction, according to the results.

Compared with the placebo group, patients assigned lebrikizumab had increased time to first asthma exacerbation for both 125 mg dose (HR = 0.37; 95% CI, 0.21-0.66) and the 37.5 mg dose (HR = 0.4; 95% CI, 0.22-0.73).

The mean number of lebrikizumab doses was 10.2 over 41 weeks. Most adverse events that occurred during the study were non-serious, mild to moderate in severity and did not lead to discontinuation of the study drug, according to the results. Eosinophil-associated treatment-related adverse events reported included decreased neutrophil count and eosinophil; there were no cases of eosinophilic granulomatosis with polyangiitis.

“In terms of safety, it was pretty comparable to what was seen in the adult studies to date,” Szefler said.

“Looking at the data … in terms of biomarkers, there was a very positive signal,” Szefler said. “Eli Lilly purchased the drug. They’re evaluating it now; they continue to study [lebrikizumab] with atopic dermatitis … [that] used higher doses and greater frequency. So, Eli Lilly is now taking a step back looking at those studies, and then deciding whether or not to pursue this. It has been interesting when I look at the inner-city asthma consortium studies, there seems to be fairly high signals for IL-13 gene activation. So, I think there’s some promise here.”

The researchers concluded that, despite the lack of a consistent dose response, post hoc analyses of adult studies (LAVOLTA I and II, MILLY) showed similar results. In addition, recently reported data from phase 3 trials of lebrikizumab in adolescents and adults with atopic dermatitis demonstrated clinical efficacy using higher doses with greater frequency, according to the researchers. Future study in asthma may need to look at optimal use of lebrikizumab with higher and more frequent dosing in patients with type 2 inflammation at risk for exacerbations, the researchers concluded.