Ipsen takes a data and patient-driven approach to rare disease research

Ipsen is a global, mid-sized biopharmaceutical company focused on building and expanding a high-value, sustainable pipeline in oncology, rare disease (RD), and neuroscience. For example, in March 2023, the company completed the acquisition of Albireo (NASDAQ: ALBO), a biotech focused on bile-acid modulators to treat pediatric and adult cholestatic liver disease with an approved RD product, Bylvay. Ipsen has executed an internal and external innovation strategy that prioritizes best-in-class technology platforms and products that can differentiate from existing treatment options or fill unmet patient needs. We spoke with Ipsen’s Senior Vice President and Global Head of Rare Diseases, Dr. Jennifer Schranz, about what she considers best practices in navigating the challenging and fast-changing rare disease space.

Every few years, we refresh our rare disease strategy

At Ipsen, we undertake a strategy refresh every two years, which includes a rigorous examination of the rare disease regulatory and policy environment and our evolving portfolio. We set the bar high for internal programs and the acquisition of external assets. Programs we invest in—or sustain investment in—must be potential game changers based on transformational or disruptive technologies. First-in-class or best-in-class products make the biggest impact for patients and fare best in the current market. 

We define unmet need with a cross-functional group that includes scientists, clinicians, regulatory, market access, patient affairs, and other experts. We focus on conditions with no or few approved therapies available where there is a well-defined mechanism of action and preclinical data. We hone in on epidemiology to determine the possibility of developing and delivering an innovative treatment in this area. Is it rare or ultra-rare? Is the natural history of the disease well understood? Are there patient registries? Are there established patient advocacy groups that will provide a patient journey and advise on clinical endpoints? Will we need to conduct a natural history (NH) study or rely on disease registries to inform clinical development? For example, first-in-class products often require an NH study to ensure we have captured endpoints that are both clinically meaningful and relevant to patients, and acceptable to regulatory authorities. We also examine the current standard of care, the landscape of existing and future competitor treatments, and whether there are well-established regulatory and reimbursement pathways. Finally, we prioritize disease-modifying treatments over symptomatic ones to truly impact the course of the disease.

It’s an exhaustive process; it takes discipline and passion to do regularly. But we take it seriously because making wise advancement decisions is critical to the patients whose lives we hope to improve and our sustainability as a company. At Ipsen, our focus and areas of strength in rare diseases include; musculoskeletal (bone), metabolic, endocrine, gastrointestinal (liver) and neuromuscular disorders. Still, any company can apply these concepts to a strategy refresh in their area of focus. 

We consult patients to design efficient and relevant trials

We’ve found that involving patients in our protocol design process, especially in the procedures and assessments schedule, and identifying which quality of life data matters to them is valuable. Patients get fatigued if we put too many procedures or tests into the protocol. But we must balance practicality and pragmatism for patients with what regulators will allow. In general, secondary endpoints—such as the number of debilitating disease-related events per day or week—may be more important to patients than biomarkers, such as blood values or an imaging procedure. In contrast, regulators focus on primary endpoints that can be objectively measured. To gather patient insights, we invite patients to review a trial’s consent forms, schedule of assessments, and other study materials. We also conduct Patient Advisory Boards to understand the patient journey and to ensure endpoints are clinically meaningful and feasible in a clinical trial setting.

And Ipsen recently conducted a patient-led symposium at a scientific congress. A clinician moderated the session, and primary biliary cholangitis (PBC) patient advocates spoke directly to the scientific audience. The seminar was called “The Person Behind the Chart.” We wanted to give a voice to PBC patients on what it’s like to live with that disease. The patient voice is increasingly persuasive for regulators, health technology assessment (HTA) agencies, and clinicians. We see this, especially at the FDA, where their series of Patient-Focused Drug Development public meetings and their policy of allowing patients to speak at Advisory Committee meetings have given an open forum to patients. The testimony and data presented at these gatherings have reshaped the agency’s thinking in some cases.

We see long-term benefits from investing in site education and training

One challenge in rare disease drug development is the ratio of sites to patients needed for a study. You may have to educate and train many sites to find one patient and ensure ample consideration for that patient’s and family’s circumstances to allow travel to the study site for procedures. It is critical to understand that patients may have mobility issues and live in remote areas. Sites are not clinical trial factories, and preparing each one to run compliant clinical research studies takes a lot of effort. Nurses, study coordinators, logistics support staff, and clinicians need to be up to speed on good clinical practice guidelines and regulatory requirements, including some practices that may run counter to how they currently care for patients. But we’ve found a tremendous benefit for the common good because the training and education invested in a site elevate that locality scientifically and increase patient access. In addition, it prepares sites to administer new products in expanded access programs even if they don’t ultimately participate in the trial.

First-in-class or best-in-class products make the biggest impact for patients and fare best in the current market.

For us, randomized controlled trials remain the gold standard

Although NH studies can inform endpoint selection—including patient-reported outcomes—we've learned that there is nothing as convincing as data from a placebo-controlled trial. Of course, enrolling a placebo control arm is sometimes hard or impossible. Crossover studies are not always possible. Although the FDA has issued a guidance document on using an NH study as an external control for open-label single arm trials, we’ve found many unresolved methodological and statistical issues. There will always be questions on whether the patients are truly matched, even when patients serve as their own control. And if you have an ultra-rare population of patients that you first enroll in an NH study and then enroll in a pivotal clinical trial, the disease may have progressed over that time period to the point where you are not studying the same condition. Also, retrospective NH studies necessitate a lot of theoretical matching and modeling. RCTs remain the gold standard. 

We communicate with integrity, even for tough decisions

Sometimes we must make difficult decisions about assets in our pipeline, even terminating programs. If safety signals emerge during development or the risk-benefit profile of a product changes due to the potential for adverse events versus efficacy gains, we explain those tough decisions to patients and investigators. But we always put the safety of patients first, and we treat them with the respect and honesty they deserve. High integrity sometimes means communicating disappointing news with transparency, even when you know that patient organizations are waiting for this news with bated breath. This is not a conversation we want to have, which is why we take our due diligence so seriously, are thorough in our asset selection, and always listen to and act on the needs of the patients.

We've found that involving patients in our protocol design process, especially in the procedures and assessments schedule, and identifying which quality of life data matters to them is valuable.

Contributing Expert