4 Takeaways From Building A Differentiated Franchise In Clinical Immunology
By Pete Salzmann, MD, MBA, CEO, Immunovant
Autoimmune diseases affect as much as 4% of the world’s population.1 There are at least 80 types of autoimmune diseases, which are chronic, unpredictable, and often have debilitating conditions, with symptoms that can wax and wane.2 Despite treatment advances, available therapies don’t always sufficiently control symptoms and can be difficult to take — either due to side effects or requiring administration by infusion, which can mean clinic or hospital visits for people living with the disease.3,4,5
It’s in this context that Immunovant was founded, with a clear and simple vision: enable normal lives for people with autoimmune diseases. A common thread through our community conversations is a desire for life to return to “normal” — without interruptions from disease and, just as importantly, from treatment. “Normal” sets a high bar — it means achieving more than incremental improvements and leaving patients with a noticeable impact.
It’s this vision that’s powering our efforts to develop a broad portfolio of neonatal Fc receptor (FcRn)--targeted therapies to meet the complex and variable needs of people with autoimmune diseases. While we are a young company, founded in 2018, we are currently running five studies — three of which are pivotal — across four different autoimmune indications. On reflection, several key factors have allowed us to achieve this significant progress — and could serve to help others desiring a similar path.
1. Build a scalable infrastructure led by seasoned executives and exceptional talent.
While it’s critical to build a bench of senior leaders who have deep drug development and commercialization experience, we know that’s not enough. It’s equally important for companies to hire employees who have the passion, drive, and resourcefulness to pivot quickly and capitalize on new opportunities. Other key criteria to consider when building a team include people who align with a company’s values, have diverse experience, and are curious and open-minded about trying innovative approaches.
2. Focus on a validated target that has broad applicability to potentially address a large market.
While there has been a lot of innovation in autoimmune disease, there’s been markedly less in conditions that are autoantibody-driven. Autoantibodies vary from person to person, which has historically made it difficult to develop targeted therapies. The emergence of the anti-FcRn mechanism has provided a unique approach to targeting autoantibody conditions.
Immunovant is developing anti-FcRn therapies that reduce harmful immunoglobulin G (IgG) autoantibodies. Rapid and deep IgG reduction consistently correlates with clinical efficacy, as has been shown by Immunovant and other companies, which can guide and expedite drug development. FcRn is now a validated target following the regulatory approval of efgartigimod and rozanolixizumab for myasthenia gravis.
Drug development is a fine balance between potential and unknowns. Biomarkers, like IgG reduction in autoimmune disease or dystrophin in Duchenne muscular dystrophy, can play a key role in focusing efforts for the best chance of success. Identifying and characterizing a strong biomarker isn’t easy, but this upfront work can pay big dividends down the road in terms of speeding innovation to patients.
In addition to the relatively straightforward biology of anti-FcRns, there is a large potential market for these therapies. One of the reasons that I joined Immunovant in the first place was because I was so impressed by both the number of autoimmune diseases where harmful IgG autoantibodies play a role and also the sheer number of people affected. Most of these people are treated with older, broad-spectrum immunosuppressants or intravenous immunoglobulin (IVIg). With 22 indications across the anti-FcRn class announced or in development, there is considerable opportunity.
Guided by a biomarker in a proven mechanism, others may find it helpful to consider several factors to assess future market potential. These include the addressable population, the unmet patient need, competitive differentiation, technical success probability, and the regulatory pathway.
3. Anchor product development to patient needs.
Industry has become so conditioned to the term “patient centricity” that its true meaning is sometimes easy to gloss over. Our clinical development programs are anchored in the patient experience, which includes the desire for more freedom during treatment. Our two product candidates, batoclimab and IMVT-1402, were “born sub-Q,” meaning that from the outset, they were designed for simple subcutaneous administration so patients may ultimately take them at home.
We also heard from patients and physicians about the fluctuating severity of many of these autoimmune conditions and that newer treatments, which generally come in a single dose, are often not sufficiently flexible for controlling their symptoms. For example, our 2023 patient survey of Graves’ disease patients with unstable disease and diagnosed over 18 months showed that up to one-third of people are unable to control their symptoms despite treatment with anti-thyroid drugs.6 Similarly, 70% of people with myasthenia gravis (MG) currently on treatment, including recently approved therapies, say their disease isn’t well controlled — often due to disease fluctuations.7
It's essential for companies, even when entering an established market, to conduct their own patient surveys or partner with patient advocacy groups or medical associations to ensure they fully understand the patient journey and to truly appreciate points of tension for people with the condition. We have also found convening patient advisors and committing to ongoing dialogue with patients and advocates informs our daily work.
Across our clinical development programs, we are studying tailored dosing strategies so that treatment regimens can be responsive to patient needs and help alleviate symptoms when patients experience flares. In MG, this includes higher induction doses to achieve short-term maximal IgG suppression for initial disease control and lower doses for more sustainable long-term control. This is a proven approach in many immunology indications, but it was a new approach when it came to the anti-FcRn class.
4. Bring innovation to clinical program design and execution.
Because it’s critical to bring new treatment options to market as quickly as possible, we realized the importance of de-risking our trials through innovative trial design. As mentioned, our Phase 3 FLEX study is the first to incorporate a flexible design in MG, although it’s a common approach in immunology.
Another example is our work in chronic inflammatory demyelinating polyneuropathy (CIDP), an autoimmune condition that is both frequently underdiagnosed and misdiagnosed. Given the importance of getting appropriate patients into the trial, our Phase 2b trial of batoclimab includes the use of a diagnostic algorithm that aims to ensure all participants have confirmed CIDP. It also uses three separate patient enrichment strategies to select participants with active, progressive CIDP who are more likely to respond to treatment. Finally, it is designed to analyze participants with different treatment histories separately, to help researchers more clearly understand what types of people with CIDP will benefit the most from anti-FcRn treatment.
Building these checks and balances will help us answer outstanding questions about CIDP, inform future clinical trial design, and ultimately maximize our chance of success. Drug development can enable the study of critical scientific questions about the biology of disease and how treatment can be optimized in the future.
References:
- National Stem Cell Foundation. Autoimmune Disease. Available at: www.nationalstemcellfoundation.org/glossary/autoimmune-disease/. Accessed January 2023.
- National Library of Medicine. Autoimmune diseases. Available at: https://medlineplus.gov/autoimmunediseases.html. Accessed January 2023.
- Lallana E et al. Toxicities of immunosuppressive treatment of autoimmune neurologic diseases. Curr Neuropharmacol. 2011.
- Bartalena L et al. Management of Graves’ Ophthalmopathy: Reality and Perspectives. Endocrine Reviews. 2000.
- Smith et al. Graves disease. N Engl J Med. 2016.
- Immunovant Patient Survey, 2023.
- Health Union. The 2022 Myasthenia Gravis in America Survey. Survey conducted June 13, 2022 and August 9, 2022.
About The Author:
Pete Salzmann, M.D., MBA, is the chief executive officer of Immunovant, a member of its board of directors, and a member of the board of directors at Corbus Pharmaceuticals. Before joining Immunovant in 2019, Pete served as a global brand development leader in immunology at Eli Lilly and Company, where he had increasing roles of responsibility over almost two decades. Pete earned a B.A. in chemistry from Northwestern University, an M.D. from the University of Chicago’s Pritzker School of Medicine, and an M.B.A. from Stanford University’s Graduate School of Business.