Breaking Barriers In Rare Disease Clinical Trials

By Ben Zimmer, CEO, Priovant Therapeutics

Conducting large-scale clinical trials in rare diseases presents a unique set of scientific and operational challenges. Dermatomyositis, a serious autoimmune condition affecting only an estimated five to 10 people per million each year, has historically been difficult to study at scale due to limited patient populations and complex disease management. To address this challenge, Priovant Therapeutics designed and executed the VALOR trial, which ultimately became the longest and largest interventional study ever conducted in dermatomyositis. VALOR’s results were recently published in the New England Journal of Medicine, where brepocitinib 30mg demonstrated statistically significant and clinically meaningful improvement over placebo on the primary endpoint and all nine key secondary endpoints, spanning global disease activity, muscle strength, skin involvement, physical function, and corticosteroid reduction.

Last month, the FDA granted Priority Review to brepocitinib’s New Drug Application, with a PDUFA target action date in the third quarter of 2026, underscoring both the urgency of the unmet need for a new standard of care that prioritizes rapid, sustained, steroid-sparing efficacy and the potential for this therapy to meaningfully shift the treatment paradigm in dermatomyositis. Delivering a trial of this magnitude required careful study design, deep collaboration with physicians and patient communities, and sustained operational focus.

Executing A Global Trial In An Ultra-Rare Disease

Enrolling and executing a rare disease trial like VALOR is challenging across so many dimensions. It’s difficult to enumerate every single one of these, but it mostly boils down to one big theme. In contrast to some clinical trials in more prevalent conditions, in a rare disease study, every step of the process — from site selection to patient selection to the screening process to the conduct of the clinical assessments — requires an artisan’s touch from an expert who is deeply invested and committed to ensuring high-quality outcomes at each step. Identifying, inspiring, and motivating a group of hundreds of such individuals across the sponsor, key vendors, patients, and study site teams around the world is not a straightforward exercise. We put a huge amount of effort into this.

Designing A Study For Meaningful Long-Term Outcomes

Our true north was always to prioritize what would make the study results most meaningful to patients in the real world - not what was easiest to execute. This is easy to assert as a principle, but much harder to actually implement in the real world, and not always the default in sponsor behavior (or human behavior, more generally!).

One of the clearest examples was our decision to conduct a 52-week placebo-controlled study with a 52-week primary endpoint. Previous dermatomyositis trials generally had a shorter 16-week or 24-week primary endpoint. FDA regulators recommended a 52-week endpoint, and we also felt this design would make our study results as meaningful as possible to clinicians and patients by evaluating not just short- to medium-term impact of the drug, but also its ability to provide sustained, durable benefit over time.

This decision came with real tradeoffs. Asking patients with a severe disease such as dermatomyositis to risk being on placebo for a full year is inherently difficult. Many believed this design would be infeasible. Yet the durability of the results, including sustained improvements through Week 52 and meaningful corticosteroid tapering, ultimately validated this approach.

We ultimately were able to overcome this through complementary design decisions (such as allowing patients who needed it to go on rescue therapy and accounting for this in the primary analysis by treating patients who required rescue therapy as non-responders) and tenacity in execution. I am so grateful to the patients who agreed to participate in a one-year placebo-controlled trial to help advance the development and understanding of new medicines for all patients.

Keeping Patients Engaged In A Year-Long Study

Despite the challenges of the one-year trial mentioned above, we achieved fairly low dropout rates in the trial. There wasn’t a single magic-bullet tactic we used to achieve this. It really comes back to the big picture — ensuring everyone involved in the study (including patient advocacy groups and patient thought leaders) brought an appropriate level of intensity and passion to what we were all collectively working toward. This sort of intensity and positive energy was contagious, and may have helped inspire patients to remain committed throughout the full study.

A culture that supports this level of care and dedication is built intentionally through clarity of purpose, hands-on leadership, and alignment across all stakeholders. In rare disease, when teams understand what’s truly at stake for patients, it creates intrinsic motivation that goes beyond a typical job. That has to be reinforced by leaders who stay close to the work — not delegating at arm’s length — and by hiring and partnering with people who bring urgency, ownership, and resilience. Consistent communication, shared accountability, and a focus on solving small problems quickly keep teams aligned, while a sense of momentum and belief builds over time. When done right, that intensity becomes self-reinforcing and extends beyond the company to investigators, patient communities, and ultimately patients themselves.

This collective commitment helped sustain engagement and ultimately contributed to the robustness of the dataset.

The Role — And Limits — Of Digital Tools In Rare Disease Trials

We used a number of digital engagement tools to help with enrollment. Some of these involved utilizing third-party vendors, but our most successful digital tool was one we built ourselves. That said, rare disease trials ultimately need to be enrolled primarily with patients already under the care of expert physicians at study sites, rather than through third-party referrals from digital tools or otherwise. Dermatomyositis is a complex and highly morbid condition and, from both the physician and patient perspective, the entire process goes best when the investigator and patient are not meeting for the first time at a study screening visit.

Partnering With The Patient And Physician Community

We worked very closely with patient advocacy groups and other patient leaders starting on day zero — from the very early stages of study design through the study readout and beyond. This played a critical role in helping to raise awareness about the trial and its importance. I am certain this helped with both enrollment and retention.

We also worked very closely and directly with physicians who treat dermatomyositis and their teams — again, starting with the very early stages of study design through analysis and communication of the data after the study was completed. They, like the patient groups, provided critical input into study design and analysis. Having these direct relationships with sites during the study (not intermediated through vendors) also allowed us to hear directly from them about their enrollment and study execution experiences. We jointly problem-solved how to overcome every micro-bottleneck, and that’s a big part of what enrollment success requires — just overcoming thousands of tiny tactical bottlenecks each week, not some single “eureka” insight.

Lessons For Sponsors Running Rare Disease Phase 3 Trials

My biggest advice would be to not fall into the trap of over-delegation. Don’t over-delegate to vendors and, even within the sponsor, make sure the top executives and drug developers at the company are hands-on, not on the golf course or TED talk circuit. A “9 to 5 only” mindset is a death knell for a rare disease study.

The reality is rare disease trials can’t be enrolled or properly executed without physicians and study teams at centers of excellence (which are most frequently academic medical centers) putting significant time and effort into the trial. However, as much as these centers of excellence care about the study, their attention is inevitably pulled in multiple directions — their physicians spend many hours in clinic, teaching residents/fellows/med students, and leading their own research projects in addition to working on therapeutic trials. If the sponsor team that owns the investigational medicine is not willing to work day-and-night to bring it to patients, how can we expect others to?

About The Author:

Ben Zimmer has been CEO of Priovant since the company’s creation in 2021. Prior to joining Priovant, he served on the leadership team of Roivant as acting COO (2018-2019) and president, Roivant Health (2018-2021). In this role, Ben led the incubation, launch, and board oversight of Datavant (majority stake acquired by New Mountain Capital), Sinovant (included in Roivant-DSP transaction), and VantAI. From 2015-2018, Ben worked at Roivant in a variety of roles across business operations, clinical operations, and public affairs. Before Roivant, Ben founded and ran a public policy-focused nonprofit and worked as a consultant at McKinsey. He holds an A.B. in history from Harvard College and a J.D. from Yale Law School.