Selecting the right endpoint for a clinical trial can make or break a drug’s success. But it can also exclude unique patient groups with high unmet needs, especially in the rare disease space.
For example, drug developers often exclude non-ambulatory patients from neuromuscular studies because they can’t measure their progress using common endpoints like the six-minute walk test or the four-stair climb. BridgeBio took a different approach, however, when the company designed its phase 2 study for BBP-418, an oral investigational treatment for limb-girdle muscular dystrophy type 2I/R9. At the urging of the LGMD patient community, the trial’s participation criteria included both ambulatory and non-ambulatory patients, according to patient advocate Kathryn Bryant Knudson.
That change might not have happened without high involvement with a patient advocacy group.
“That is a clear example of where they were listening to the patient voice,” said Knudson, CEO and founder of the LGMD patient advocacy organization The Speak Foundation who is also an LGMD patient herself. “We wanted to have non-ambulatory patients to have the opportunity to take BBP-418.”
If it’s OK’d, BBP-418 would be the first approval of a therapy for any form of LGMD. Its scheduled PDUFA date is Nov. 27.
Patient-centered drug development has become a larger goal in pharma in recent years, with the FDA encouraging sponsors to incorporate it throughout the regulatory process. Large companies like Pfizer and Astellas Pharma have also highlighted their work in this arena.
“I think we need to include patients in any kind of development discussions with FDA."
Kathryn Bryant Knudson
CEO, founder, The Speak Foundation
The benefits are well-known. Tapping patients can help speed and improve trial recruitment, potentially increase participant diversity and influence trial endpoints. This is especially important in rare disease, where patient populations are limited and endpoints can be hard to measure.
But pharma and biotech companies still often miss the mark when it comes to bringing patients into the R&D fold. According to a Rare Patient Voice survey of more than 2,000 respondents, 69% were unaware that clinical trial co-design exists and just 4% had participated in it. Additionally, an FDA-backed report found mentions of patient experience data in regulatory review documents for about 73% of 315 original new molecular entity drug applications and original biologics license applications approved between Feb. 5, 2021, and Dec. 31, 2025.
Getting patient involvement right
Since launching The Speak Foundation in 2008, Knudson has watched the LGMD drug R&D pipeline grow to include multiple new candidates from different biotechs. She’s also learned how pharma and biotech companies can best incorporate the patient voice into drug development. In the best case scenario, it starts in the earliest stages.
“We need to engage patients before the protocol and evidence plan are fixed,” she said. “We need to be involved because we can inform a lot of these decisions.”
For instance, calling for ambulatory patients in a trial’s inclusion criteria might sow confusion among patients who only occasionally use a wheelchair about whether they’re eligible to participate, Knudson said. When companies incorporate that patient feedback into the trial design from the very beginning, they avoid creating unnecessary gray areas for patients, and then costly delays or revisions.
“I've seen many trials where recruitment has been a challenge, and then later on [sponsors] coming back to the patient community and realizing that there was an issue with trial design,” she said.
Knudson also believes that the patient voice belongs at the regulatory table throughout the development process. And often, highly educated patients can speak to both the patient experience as well as the science.
“I think we need to include patients in any kind of development discussions with FDA,” she said.
She again points to her experience with BridgeBio, which “brought the community in from the start, before the first patient was ever given a dose,” she said.
“Patients helped shape the design of the early phase 2 study, then we partnered directly on the phase 3 protocol, giving input and feedback on endpoints, visit burden and eligibility criteria,” she said. “We were also part of BridgeBio's FDA engagements from early on, so the agency heard the unmet need and urgency directly from patients and families, not secondhand.”
Drug developers also often fail to account for the burdensome challenge of collecting natural history data, which track how a disease progresses over time, especially among small pools of rare disease patients, Knudson said.
“Patients are not a renewable resource,” Knudson said. “Rare disease communities have very few eligible participants, and when we start any kind of clinical trial, the same people in our community are repeatedly asked to contribute blood, tissue, biopsies, data and time. And our health, energy and our participation are finite.”
Instead of repeatedly asking the same patients to contribute natural history data, Knudson encourages sponsors to “inventory existing data before requesting more from patients” and even share data sets.
As she awaits the upcoming PDUFA date for BBP-418, Knudson is continuing her advocacy, joining patients on Capitol Hill this week for The Speak Foundation’s annual LGMD Day on the Hill.
“We see professionals speaking for the patients, which never works,” she said. “You have to have the authentic voice of the patient.”
