Enhancing Autoimmune Care: Caterina Brindicci from AstraZeneca in a Riveting Conversation with PharmaShots

Shots:

SLE-related diseases like CLE and IIM are characterized by strong type I interferon involvement. The proven efficacy of Saphnelo (anifrolumab) in SLE lays the foundation for its potential use in CLE and IIM

Recently, AstraZeneca initiated two new P-III trials, LAVENDER and JASMINE, to evaluate Saphnelo in cutaneous lupus erythematosus and idiopathic inflammatory myopathies

Caterina Brindicci, SVP and Global Head of R&D, Respiratory & Immunology at AstraZeneca, discusses the study designs and outlines the primary endpoint criteria for both conditions.

Saurabh: AstraZeneca announced the initiation of two new Phase III trials evaluating Saphnelo – in cutaneous lupus erythematosus (LAVENDER) and in idiopathic inflammatory myopathies (JASMINE). Would you like to share the study design of JASMINE and LAVENDER?

Caterina: The LAVENDER Phase III trial is a multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous anifrolumab in adults with chronic and/or cutaneous lupus erythematosus (CLE). The primary objective of the study is to evaluate the efficacy of anifrolumab, compared to placebo, in reducing skin disease in approximately 460 adult participants.

JASMINE is a Phase III, multinational, randomized, double-blind, placebo-controlled study expected to enroll approximately 240 patients aged between 18 to 75 years with polymyositis or dermatomyositis. JASMINE will evaluate the efficacy and safety of subcutaneous anifrolumab in adult patients with moderate to severe polymyositis or dermatomyositis while receiving standard-of-care treatment.

Saurabh: Both CLE and IIM are orphan and rare indications. What makes Saphnelo a good option for these indications?

Caterina: CLE and idiopathic inflammatory myopathy, namely polymyositis, and dermatomyositis, are autoimmune diseases related to abnormalities in an immune pathway involving type I interferon. Dysregulation of the type I interferon pathway causes a range of both prevalent and rare autoimmune diseases. As you say, these are rare conditions, with idiopathic inflammatory myopathies (IIM) affecting approximately 1-8 people per 100,000, while CLE affects approximately 70 people out of every 100,000.

Anifrolumab is the first-in-class and currently only approved biologic targeting type I interferon, a central driver of systemic lupus erythematosus, in over a decade. The initiation of these trials is an important step forward in our ambition to help more patients with diseases where type I interferon is thought to be a central driver.

Anifrolumab could have the potential to meaningfully improve the lives of people living with these chronic, progressive autoimmune diseases, as has been demonstrated by favorable trial results seen in the TULIP trials for Systemic Lupus Erythematosus (SLE). In the Phase III TULIP-2 trial, anifrolumab not only met its primary endpoint of reduction of SLE activity but also demonstrated benefit in lupus-associated skin disease, with nearly half of patients in the anifrolumab treatment group having a ≥50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score vs 25% in the placebo group after 12 weeks of treatment.17 The reduction in skin disease severity indicates that anifrolumab is effectively suppressing the activity of interferon kappa, which is typically overexpressed in lesional and non-lesional skin of those with SLE. Similarly, the type I interferon gene signature is typically overexpressed in the blood and muscle of patients with IIM and corresponds with disease activity. Anifrolumab has the potential to have a similar effect in IIM, as has been seen in SLE.

Saurabh: Can you discuss any studies or data (RWE etc.) suggesting Saphnelo could be a fit for CLE and IIM?

Caterina: Based on anifrolumab’s unique mode of action and data collected so far, we believe it has the potential to be an important advancement in the treatment of type I interferon-implicated diseases, which could meaningfully improve the lives of patients.

CLE and IIM are SLE-related diseases characterized by strong type I interferon involvement. The most compelling evidence for anifrolumab development in CLE and IIM is provided by its proven efficacy in SLE, which is also characterized by increased IFN-1 signaling.

Additionally, two case studies looking into the effect of anifrolumab in discoid lupus erythematosus, a form of CLE, and dermatomyositis demonstrated evidence of efficacy in a small number of patients. In the discoid lupus erythematosus case series, eight women with discoid lupus erythematosus who had received anifrolumab for at least eight weeks saw significant improvements in symptoms and disease activity within two months of initiating anifrolumab treatment. In the dermatomyositis case study, a 43-year-old woman saw marked skin improvement following anifrolumab administration which led to near-clearing of facial activity after four doses.23

Anifrolumab is currently being investigated to determine its efficacy in CLE and IIM.1,2 Phase III results are expected following study completion in 2028.1,2

Saurabh: What primary endpoints are you targeting in patients of JASMINE and LAVENDER?

Caterina: LAVENDER is a two-stage, Phase III study to investigate the efficacy and safety of anifrolumab in adults with chronic and/or subacute cutaneous lupus erythematosus. In the US, the primary endpoint is the number of patients with Cutaneous Lupus Activity of Investigator’s Global Assessment-Revised (CLA-IGA-R) erythema score of 0 or 1, and at least a 2-point reduction relative to baseline, at week 24. In the EU/rest of the world (ROW), the primary endpoint is the number of patients with a 70% reduction relative to baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score. LAVENDER study details can be found on the ClinicalTrials.gov websit e.

JASMINE, a study to investigate the efficacy and safety of anifrolumab administered as a subcutaneous injection and added to the standard of care compared with placebo added to the standard of care in adult participants with IIM (polymyositis and dermatomyositis). In JASMINE, the primary endpoint is the proportion of patients who have at least moderate improvement in disease activity, a Total Improvement Score (TIS) equal to or greater than 40, and have not met "confirmed deterioration" criteria at 2 consecutive visits by week 52. JASMINE study details can be found on the ClinicalTrials.gov website.2

Saurabh: When do you expect to see initial results from both studies?

Caterina: Both LAVENDER and JASMINE studies are expected to be completed in 2028 with results following thereafter.

Saurabh: What are the other treatment options available for CLE? What are the unmet needs and how can Saphnelo address those unmet needs?

Caterina: As mentioned, CLE affects approximately 70 people out of every 100,000 and has high unmet need. Treatment options tend to be based on broad immunosuppressants and oral corticosteroids, namely rituximab, which is non-disease-specific.

There are no licensed treatments currently available for CLE. Topical and systemic agents in CLE are mostly applied ‘off-label’ and are rarely supported by evidence from randomized clinical trials.

Based on anifrolumab’s unique mode of action and data collected so far, we believe it has the potential to be an important advancement in the treatment of type I interferon-implicated diseases, which could meaningfully improve the lives of patients. AstraZeneca has clinical programs at different phases of development to investigate CLE, and the molecules under investigation have unique mechanisms of action targeting the disease.

Saurabh: What are the other treatment options available for IIM? What are the unmet needs and how can Saphnelo address those unmet needs?

Caterina: As mentioned, idiopathic inflammatory myopathies affect approximately 1-8 people per 100,000 and have high unmet needs. Treatment options are very limited, with immunoglobulin (IVIg) acting as the only approved treatment for dermatomyositis. Though it has been approved for dermatomyositis, a targeted treatment for polymyositis has not yet been approved. AstraZeneca is investigating idiopathic inflammatory myopathies and has clinical programs at different phases of development targeting specific subtypes of the disease.

Image Source: Canva

About the Author:

Caterina Brindicci

Caterina Brindicci is Senior Vice President & Global Head for Late Respiratory & Immunology at AstraZeneca. She is committed to transforming care for those living with Respiratory and Immune-Mediated diseases by bringing new therapies to market and collaborating with partners to ensure equitable access. Caterina plays a vital role in AstraZeneca’s bold sustainability programme, accelerating the clinical development of a new propellant that will ensure climate-friendly, next-generation respiratory inhalers for millions of patients across the globe.