Priya Singhal, Senior Vice President at Biogen, Shares Insights from Litifilimab Systemic Lupus Erythematosus NEJM Publication

Shots:

Priya spoke about the study design and key findings from the P-II (LILAC), P-III (TOPAZ-1) & (TOPAZ-2) clinical study evaluating litifilimab
She also talked about the P-III trial evaluating Dapirolizumab pegol in collaboration with UCB to treat SLE
The interview summarizes how Biogen’s innovative medications are helping patients with Systemic Lupus Erythematosus which has limited treatment options

Smriti: Explain the details (MOA, ROA, formulations, etc.) of litifilimab?

Priya Singhal: Litifilimab, discovered and developed in-house by Biogen scientists, is a subcutaneously delivered, humanized IgG1 monoclonal antibody (mAb) targeting blood dendritic cell antigen 2 (BDCA2) and is being investigated for the potential treatment of systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE).

Litifilimab targets a receptor that is predominantly expressed on immune cells called plasmacytoid dendritic cells (pDCs), which are found at the site of inflammation in key organs affected by lupus including the joints and skin.

Smriti: Please give us a brief detail about the study design of the P-II (LILAC), P-III (TOPAZ-1) & (TOPAZ-2) clinical study evaluating litifilimab.

Priya Singhal: LILAC: LILAC was a Phase 2, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of litifilimab in two parts: Part A in individuals who have SLE with active joint and skin manifestations; and Part B in active CLE, including chronic and subacute subtypes, with or without systemic manifestations. Note, this Phase 2 trial was not powered to assess secondary endpoints.

The primary endpoint of Part A measured total active joint count, which is defined as the sum of the tender and swollen joint counts, using the change from baseline to Week 24 in participants treated with either 450 mg litifilimab or placebo.
The primary endpoint of Part B measured skin disease activity using the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-A) score from baseline to Week 16 across the four litifilimab dose groups (placebo, 50 mg, 150 mg, and 450 mg).

TOPAZ-1 and TOPAZ-2: The Phase 3 TOPAZ studies are interventional, multicenter, randomized, double-blind studies to evaluate litifilimab compared with placebo in adults with active SLE who are receiving background lupus standard of care therapy in reducing disease activity.

The primary endpoint of both TOPAZ-1 and TOPAZ-2 will measure SLE Responder Index-4 (SRI-4) response, an indicator of low disease activity, at Week 52 across three litifilimab dose groups (placebo, litifilimab low dose and litifilimab high dose).
Secondary endpoints will assess the efficacy of litifilimab compared with placebo in reducing disease activity across various measures, evaluate participant-reported health-related quality of life (HRQoL) and impacts of SLE, and safety and tolerability.
Together, TOPAZ-1 and TOPAZ-2 are currently recruiting participants at approximately 105 clinical trial sites worldwide. For more information about the TOPAZ studies, visit clinicaltrials.gov (NCT04895241) and NCT04961567.

Smriti: Give our readers an overview of the key findings obtained from the P-II (LILAC) clinical study.

Priya Singhal: Results from the SLE portion (Part A) of the LILAC study show litifilimab met the study’s primary endpoint by significantly reducing total active joint count compared to the placebo. The total active joint count is one of the most common SLE symptoms experienced by lupus patients.

Litifilimab also met the primary endpoint in the CLE portion (Part B) of LILAC by demonstrating superior efficacy to placebo in improving skin disease activity in participants with CLE. A significant dose-response relationship based on the percent change from baseline in the CLASI-A score at Week 16 was observed.

Taken together, the two publications further illustrate the body of evidence supporting the continued development of litifilimab. The Part A and Part B manuscripts were published separately in the New England Journal of Medicine (NEJM) on September 8, 2022, and July 28, 2022, respectively.

Litifilimab was generally well tolerated in both parts of the trial, with most reported adverse events (AEs) rated as mild or moderate. In Part A, the most common AEs reported (≥5% of participants) in the pooled litifilimab groups were diarrhea, nasopharyngitis, urinary tract infection, fall, and headache. Adverse events that led to drug discontinuation were observed in two participants who received BIIB059 and three participants who received a placebo.

The most common AEs reported in Part B (≥5% of participants) in the pooled litifilimab groups were nasopharyngitis, headache, injection-site erythema, SLE, arthralgia, upper respiratory tract infection, influenza, pruritus, cough. Adverse events that led to drug discontinuation were observed in eight participants who received BIIB059 and no participants who received a placebo.

Smriti: Kindly share some updates on the TOPAZ-1 & 2 studies as well i.e., recruitment status, timeline, expected results, and subsequent filing and approval.

Priya Singhal: Biogen is currently enrolling participants into the TOPAZ-1 (NCT04895241) and TOPAZ-2 (NCT04961567) studies which will evaluate the efficacy and safety of litifilimab compared with placebo in participants with active SLE. The TOPAZ studies aim to include approximately 1,080 adults with active SLE at 269 clinical trial sites worldwide.

As part of Biogen’s commitment to delivering diversity in its clinical trials, enrollment targets have been set in the TOPAZ studies to achieve appropriate representation of the African American and Hispanic/Latino communities. We look forward to continuing our evaluation of litifilimab in late-stage studies to further evaluate its potential, particularly in those who historically have been underserved.

Participants who complete either TOPAZ study are eligible to enroll in Phase 3 open-label extension study, which will continue to evaluate the long-term safety and tolerability of litifilimab in active SLE.

Smriti: Shed some light on the P-III trial evaluating Dapirolizumab pegol along with the key finding so far obtained over the evaluation period. Also, tell us about your collaboration with UCB for the development of Dapirolizumab pegol.

Priya Singhal: Biogen is collaborating with UCB to advance the development of dapirolizumab pegol, an investigational humanized monovalent pegylated Fab antibody fragment against the CD40 ligand (CD40L). Dapirolizumab inhibits CD40–CD40L interactions and is believed to suppress inflammation by reducing T cell and plasmacytoid dendritic cell (pDC) activation, the production of pathogenic autoantibodies, and inflammatory events that can lead to organ damage accrual.

Biogen and UCB’s Phase 3 trial of dapirolizumab pegol (NCT04294667) began in 2020 and is ongoing. Its purpose is to evaluate dapirolizumab pegol as an add-on treatment to standard-of-care medication for active SLE – such as corticosteroids, anti-malarials, and non-biological immunosuppressants – to achieve clinically relevant long-term improvement of moderate-to-severe disease activity. We will share the results of this study when available.

Smriti: Are there any pipeline products (incl. early stages) being assessed/ expected to be in any type of Lupus?

Priya Singhal: Despite significant advancements over the past 20 years in treating autoimmune indications, there is still a significant unmet medical need in lupus and adjacent serious autoimmune diseases.

At Biogen, our goal is to discover and develop new treatment options that not only reduce lupus disease activity but also decrease clinical manifestations that impact patients the most. We are investing in our pipeline and capabilities, leveraging decades of study on pathways at the intersection of neurology and immunology, to impact the lives of people living with serious autoimmune diseases such as lupus. We have the potential to develop the first lupus portfolio in the industry with first-in-class therapies in SLE and CLE.

Smriti: As the products in Phase 3 what HCP engagement and education programs are ongoing? Also, let us know about any digital initiatives or engagements for the same.

Priya Singhal: Since lupus mainly affects minority populations, Biogen and UCB have provided culturally sensitive training for HCPs participating in our studies. We also provide HCP-specific training modules on the disease state, unmet needs, and mechanism of action while leveraging vendors and site networks in providing training to support the HCPs.

Our digital initiatives include media tactics based on geography, demographic data, and market performance. We also provide online outreach with a study website and referral support to assist sites with recruitment.

Source: Freepik

About the Author:

Priya Singhal is the Senior Vice President (S.V.P.) and Head of Global Safety and Regulatory Sciences and interim Head of Research & Development at Biogen. She also has oversight of Japan and China R&D. In her role as S.V.P. she managed the worldwide benefit-risk strategy for the portfolio as well as for the filings and approvals of six products. She joined Biogen in late 2012 as Vice President of Clinical Trials and Benefit-Risk Management. Dr. Singhal completed her M.P.H. in International Health at Harvard School of Public Health and obtained her training in Internal Medicine in Mumbai, India.