Maximizing Success in Rare Disease Studies

Moe Alsumidaie interviews Sanjay Shukla, MD, MS, CEO of aTyr Pharma, about the company's clinical operations and ongoing Phase III study for pulmonary sarcoidosis. Shukla explains the challenges in conducting a large trial for a rare disease and the company's approach to overcoming them. The trial design, incorporating patient feedback and decentralized clinical trials, are seen as essential for clinical trial and commercialization success.

Moe Alsumidaie: Sanjay, thanks for taking the time to talk with me today. To start, could you tell me about the current state of aTyr Pharma's clinical operations and the ongoing Phase III study for pulmonary sarcoidosis?

Sanjay Shukla: We are currently recruiting patients for a Phase III study of efzofitimod in patients with pulmonary sarcoidosis. This study is one of the largest trials ever conducted in this rare disease, with the goal of enrolling more than 260 patients worldwide. The goal of the study is to evaluate the safety and efficacy of efzofitimod in improving lung function and reducing symptoms in patients with pulmonary sarcoidosis, including cough and shortness of breath. Efzofitimod is an intravenous therapy that is administered through a one-hour infusion, once per month. The fast-track designation from FDA is a testament to the potential of efzofitimod and highlights the need for new treatments for this condition. Additionally, we have also received an orphan drug designation—not just in the US, but also in Europe—which is a great recognition of our efforts in developing new treatments for rare diseases.

MA: What are three significant challenges that aTyr faces in clinical operations, and how are you overcoming them?

SS: The first challenge is recruiting for such a large trial in a rare disease. We have engaged with clinical trial sites in about ten countries to participate in this trial. The second challenge is the ongoing pandemic, which has created fear and concerns for patients. Despite these challenges, we were able to finish recruiting for the last trial during the worst parts of the pandemic, thanks in part to the motivation of the patients to continue coming to the clinic. The third challenge is ensuring that we have the financial resources to carry out this trial, which is why we are fortunate to have strong investors, including groups like Fidelity, a well-known large mutual fund.

MA: Have you involved patients and investigators in the design of the protocol for the Phase III study?

SS: Yes, we have incorporated patient feedback into the design of our trial. In fact, we were the first company in the lung disease space to include a steroid reduction element in our protocol, which is directly from patient feedback. This has created a paradigm shift in the industry and has been recognized by worldwide regulators as the most critical endpoint to prioritize.

MA: Can you tell me why the trial design is essential for competitiveness and commercialization success?

SS: The trial design is essential because it focuses on what is most important to patients, which is improving their symptoms and reducing their use of steroids. We are looking at the most validated symptom indexes, such as the King's Sarcoidosis Questionnaire, which tracks cough and shortness of breath, and forced vital capacity, to measure lung function. Additionally, we are also looking at disease related inflammatory markers that have been identified as critical by medical experts. All of these are essential factors that make this trial design one that lends to commercialization success.

MA: Have you taken into account the elements of decentralized clinical trials in your study and what potential obstacles do you foresee?

SS: Yes, we can incorporate some elements into our trial. For example, we can track steroid reduction through electronic diaries in addition to in-person visits with the investigator. This element can reduce the burden of the number of times patients have to come on site as part of the study. However, for this rare disease, we are not yet at the stage where patients can perform more sophisticated tests at home.

MA: Women and some minorities are at greater risk of developing pulmonary sarcoidosis. How important is it that your clinical trials are diversified?

SS: Diversity in clinical trials is incredibly important to us. We understand that women and minorities are at a greater risk of developing sarcoidosis, and that is why we have set up our clinical trial centers in urban areas like Atlanta, Birmingham, and Washington, DC. We are also working closely with the Foundation for Sarcoidosis Research to educate patients about the importance of participating in clinical trials and to ensure that our trials are representative of the patient population. By addressing a real patient-relevant endpoint, such as steroid reduction, we are confident that our trials will be relevant and meaningful to patients, regardless of their race or gender.

MA: Capital is tight, and interest rates are rising. How do you, as a small biotech, plan to survive?

SS: We are fortunate that we raised approximately $90 million ahead of the declining financial climate, which has allowed us to maintain a healthy balance sheet of north of $70 million. Our robust investor base is confident in our ability to hit our milestones and execute our plans, which has allowed us to remain confident in our ability to get through the trial and find a cure for sarcoidosis. As a small but mighty team based in San Diego, we are committed to carefully managing our capital and focusing on our goal of developing innovative treatments for rare diseases.

MA: What motivates you to find a cure for a rare disease like sarcoidosis?

SS: As a medical student in Washington, DC, I had the opportunity to meet patients with sarcoidosis. This is where my interest in this disease began. I believe that by shining a light on this condition and raising awareness, more companies will get interested in finding a cure. As a clinician, my goal is to help patients and make a difference in their lives, and finding a cure for sarcoidosis would be a step in that direction. I hope that by getting involved in this study, we can accelerate research efforts worldwide and make a positive impact on the lives of patients suffering from this disease.

Moe Alsumidaie, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and regular contributor to Applied Clinical Trials.