Eli Lilly Steps Up Focus On Autoimmune Diseases

By Ed Miseta, Chief Editor, Clinical Leader

Managing patients having an autoimmune disease can present special challenges for researchers, from correctly diagnosing the disease to recruiting specific patients for clinical trials. I recently spoke with Chin Lee, global senior medical director in the immunology therapeutic area at Eli Lilly and Company. Lee has been with Lilly for more than six years. Prior to joining the company, he worked in the immuno-science group at Abbott Laboratories and prior to entering the pharmaceutical industry, he spent the earlier part of his career in academia, studying clinical outcomes in patients with lupus and osteoporosis at the Northwestern University Feinberg School of Medicine. He also spent time as a practicing rheumatologist while performing clinical research.

In this interview, Lee discusses his decision to move from academia to pharma and the challenges inherent in performing clinical trials on autoimmune disease patients.

Ed Miseta: Why did you decide to make the move from a practicing physician to the pharmaceutical industry?

Chin Lee: Before I joined Lilly, I was aware of the company and some of the therapeutic areas it was known for, such as diabetes and its research in osteoporosis.  However, I was less familiar with Lilly’s efforts in the autoimmune/immunology space.

One of the things that attracted me to Lilly was the ability to work on its autoimmune platform, which was an emerging therapeutic area for the company. It was an area that was internally termed “white space,” meaning the team would explore opportunities and move forward if they felt there were good possibilities to deliver medicines that would benefit patients. In my view, Lilly appeared to be very committed to establishing a research focus in this therapeutic space, and the idea of being part of this new venture represented a compelling career move.

I was one of a handful of rheumatologists at Lilly when I joined the company and we have added many more since then. It was an exciting time to join the company because the molecules being developed were in early- and mid-phase development, but we also had assets ready to move into Phase 3 trials.

Miseta: Has the company made a lot of progress in the auto-immune area since then?

Lee: We have.  One molecule, ixekizumab, recently received regulatory approval for plaque psoriasis in the U.S., European Union, and Japan, and for psoriatic arthritis in Japan. We have another molecule, baricitinib, in late-phase development. If that’s successful in gaining future regulatory approval, it should offer clinically meaningful outcomes for patients with rheumatoid arthritis. In addition, we have other molecules in the pipeline with mechanisms of action that may have a role in treating other immunologic conditions.

I’m really excited about where we are. Things are looking very promising for us, but more importantly for patients. We are not talking about drugs that will incrementally increase the levels of efficacy. For example, with ixekizumab, we are seeing levels of skin clearance that have not been seen before, and it represents a new therapeutic option for patients with psoriasis.

Miseta: There are many autoimmune diseases. Are all of these diseases somehow related to each other?

Lee: That’s a really good question. The simple answer is there may be a relationship between them. Under healthy states, the immune system is able to recognize what is you and what is foreign and/or harmful and appropriately respond to remove what is foreign, for example, in the case of an infection. If you look at the immune system on a spectrum, on one end you might have patients who are immunocompromised.  Examples would be those who have advanced HIV/AIDS or those patients with certain cancers who may be receiving chemotherapy. On the other end of the spectrum, the immune system may fail to appropriately recognize what is “self,” and that can result in the immune system essentially attacking the “self” rather than foreign agents. This represents what happens in the case of autoimmune conditions.

Two classic examples are lupus and rheumatoid arthritis. In those diseases, we have found there are auto-antibodies. The presence of these auto-antibodies indicate that in these patients, their immune system is mounting an immune response to some component of “self” that results in the formation of antibodies. So, conceptually, your immune system is in effect responding in a manner that is clinically detrimental to yourself, your tissue, and your body in the context of autoimmune diseases.

Miseta: Will this manifest itself in patients in different ways?

Lee: Absolutely. If you look at patients with rheumatoid arthritis, many of them have some of the similar clinical features that revolve around damage to the joints and related physical impact, such as pain and physical disability. But we find the degree of severity can vary between patients. If you look at diseases like lupus, which is more clinically heterogeneous, you have patients with very mild disease and limited organ manifestations. But at the same time, other patients may have very severe disease and life-threatening organ manifestations such as kidney failure.

Miseta: Because of these differences, is working with these diseases a challenge to researchers trying to understand it?

Lee: Yes, absolutely. If you look at the average time for these different autoimmune conditions to be diagnosed in a patient, there can be a delay. That delay can vary because some of these diseases might be easy to diagnose while others can be quite challenging. For example, if you look at patients with psoriatic arthritis, it can be mistaken for other types of arthritis such as rheumatoid arthritis, gouty arthritis, or osteoarthritis. Their complaints might even resemble something that’s more related to a musculoskeletal injury resulting from overuse.

This can lead to patients being misdiagnosed and delay the appropriate therapy. That delayed diagnosis can be a problem when running clinical trials, which depend on patients having a physician-diagnosed condition. But keep in mind that some of these immune-related conditions are more prevalent than others.  For example, psoriasis is more prevalent in the population. But if you have a condition that is less prevalent, there are a relatively limited number of available patients to be candidates for clinical trials.  Further, even patients who have a diagnosis will need to meet the entry criteria of the trial.

Miseta: So it sounds like patient recruitment becomes an even bigger challenge than it already is?

Lee: Patient recruitment is always a challenge. A certain number of patients are required to determine whether a drug is efficacious. Difficulties will arise when there is a delayed diagnosis or a misdiagnosis. Patients may not even know they have the right conditions to be included in a clinical trial. Additionally, their physician may not think about referring patients to be considered for a trial.

Miseta: To say this is a challenge for researchers seems to be a great understatement.

Lee: It can definitely be challenging. But remember it varies by disease. With psoriasis we tend to enroll our trials fairly quickly. The disease is also more prevalent than many of the other autoimmune diseases. Furthermore, psoriasis can be relatively easy to diagnose by a dermatologist.

In other programs, that is not always the case. There was a lupus program we worked on that took a long time to recruit, and the delay was related to making sure we had patients who were correctly diagnosed with that condition and also fulfilled some of the entry requirements for the study.

Miseta: Does recruitment require additional creativity on your part?

Lee: We need to be very thoughtful in how we approach the design and implementation of our clinical program from a patient, as well as the investigator perspective. I think a lot of the legwork is done upfront to identify sites where there is a higher likelihood of finding the right pool of patients. Also, an important component of the site selection process is to locate sites where there are physicians who are experienced in making appropriate diagnoses and treating these patients, coupled with investigators who have experience running clinical trials.

Additionally, we work with our sites to ensure they have the resources they need to perform the proper outreach to patients and clinical practices in their communities.

Miseta: Have you put any focus on working with patient groups?

Lee: Absolutely. From an advocacy standpoint, we work closely with organizations such as the National Psoriasis Foundation and the Arthritis Foundation to ensure they are aware Lilly is focused on the medical conditions that are important to these groups.  They can also be very helpful at disseminating trial information to their local chapters. This is helpful because when a patient receives a diagnosis, one of the first things he/she may do is try to learn more about their condition, and some may search for a support group.

I would add that when designing our trials, we need to be cognizant of the requirements to meet our endpoints and meet regulatory guidelines, but also make sure those requirements will not be onerous for sites and patients participating in our trials. There’s a delicate balance between the information we need to gather and what we can realistically expect patients to undergo in the course of a clinical trial. To better accomplish this, we have discussions with patients, advocacy groups, and industry thought leaders to understand what is pragmatic and what is not.