Spinal muscular atrophy (SMA) is a disease caused by a genetic deficiency in a gene known as SMN1. Because of that deficiency, which impacts patients early in their life, the motor neuron cells in the spinal cord are impaired or sometimes die off. That in turn leads to patients being unable to perform basic tasks such as standing or walking. The disease can be fatal without treatment.
Scholar Rock recently completed a Phase 2 proof-of-concept trial and is excited about the results and the potential it represents for patients with SMA. The company has plans to move forward with a Phase 3 trial.
“This is a very serious illness with a high unmet medical need,” says Yung Chyung, CMO for Scholar Rock. “More recently we have seen progress in this disease area with the advent of SMN (survival motor neuron) genetic targeted therapies. For patients to fully benefit from these therapies, however, they need to be initiated early in life, and even then, there continues to be further medical need. Our hope and our goal is to complement these SMN therapies by directly targeting the muscle with our molecule to increase motor function in patients.”
With SMA, researchers are faced with some unique patient recruitment challenges. Patients with SMA are geographically dispersed and come from all ethnicities. SMA is also a rare disease, which means there is not a large patient pool. There are also a limited number of clinical centers or sites with personnel who have experience with the disease.
“When thinking about clinical trials, we have to take a very thoughtful and strategic approach in regard to patient recruitment,” says Chyung. “That strategy begins before we ever get to the clinical stage. We think about recruitment when designing the trial and doing what we can to make it patient centric and eliminate potential burdens.”
A Patient Centric Approach
To better understand the patient journey, Scholar Rock partners with patient organizations. The company solicits advice from those organizations and has participated in patient focus groups to gain thoughts and insights from potential trial participants. For example, patients with SMA have physical disabilities that will make it difficult just to get to a clinic.
“Most patients with SMA are unable to walk and often need assistance from a caregiver just to get to the site,” states Chyung. “That is something we cannot take lightly. We cannot put them in a situation where they are constantly going back and forth between their home and the clinic. Since this is a rare disease, many of those patients also must travel long distances. That forces us to be efficient and thoughtful when planning the number of visits required. We had to consciously decide how many visits were needed and what needed to happen at each visit.”
Chyung notes Scholar Rock also put a lot of thought into selecting sites and what would be required of site staff. Equipment was required to perform certain efficacy assessments, and site staff generally need to be trained on using the equipment. Patients would need to navigate hallways to get to the equipment. Some thought even had to be put into the assessments that patients were required to complete. Patients with SMA are easily fatigued, which can also impact the assessments.
“The details really matter,” adds Chyung. “When a patient enters the clinic, the temptation is to get as much information as possible. But we must stop and ask ourselves what assessments we are asking our patients to do. Whatever we ask of patients and sites, we want to make sure we are thinking about the therapeutic hypothesis we are trying to address while also being patient- and site-centric. A lot of careful thought is necessary to narrow down a long list of potential assessments, prioritize them, and try to be as efficient as possible to minimize the burden on patients.”
Plan For Success
If patients had to undergo an important assessment, care was taken to ensure they were not put through other activities prior to the assessment. Any exertion on the part of the patient could later impact the assessments being performed. To avoid that situation, assessments were performed early in the visit. Other procedures, along with administration of the drug (an IV-infusion), were done later in the visit.
If patients had to travel a long distance, logistical considerations we put in place, including overnight stays at a nearby hotel. That would enable patients and care givers to recover from the travel before being asked to visit the clinic for assessments. According to Chyung, these details were planned out during the trial design phase.
“Our trial design was heavily influenced by the patient voice,” says Chyung. “Feedback from patients and patient advocacy groups were very important to us and were instrumental in the planning for the trials. Two patient groups that we worked closely with were Cure SMA and the SMA Foundation. We consider them to be true partners and they provided us with advice and many helpful insights.”
Don’t Throw Recruitment Over The Fence
Even when a lot of thought has been put into making trials site- and patient-centric, recruitment can be a challenge. Chyung notes when you are faced with a complex challenge, partners can be the best way to overcome the hurdles.
“That is not the time for sponsors to take a back seat approach,” says Chyung. “They need to be very proactive and involved. Site selection and patient recruitment should not be outsourced or delegated to a CRO alone. Our philosophy is to work closely with both the site staff, patient groups, and our CRO partner. We take pride in designing studies that eliminate burdens to both the site and patients, and that requires a lot of careful thinking.”
Site selection is an important step, and Chyung is a big proponent of deep scientific engagement with sites. He believes in having these scientific discussions with not only the site investigators, but the physical therapists as well. Those therapists are instrumental to the success of the trial. The goal is to ensure everyone understands the scientific rationale and the underlying therapeutic hypothesis being tested. If everyone at the site understands what Scholar Rock is trying to accomplish, they will be in a better position to identify patients who may be a good potential candidate for the trial.
If you’re wondering about the company name, Chyung notes co-founder Timothy Springer is a collector of scholar rocks. Scholar rocks are naturally occurring rock formations that get sculpted through time via wind and water to form interesting shapes. When the leadership team was brainstorming names for the company, they realized the sculpture of one of Springer’s scholar rocks looked like the crystal structure of one of the drug targets the company was investigating. They decided to adopt that name for the company and according to Chyung, it is always a fun conversation starter.