Beyond the usual challenge of delivering high-quality data that answers meaningful questions, PepGen’s Michelle Mellion is dedicated to “incorporating the patient’s voice into everything we do.”
Michelle Mellion, M.D./courtesy of PepGen
Michelle Mellion, M.D., newly-appointed SVP and head of clinical development at PepGen, began her career working to deliver the best possible to care to patients and education to medical students. Now she is working to ensure the patient’s voice is heard throughout the drug development process.
Beyond the usual challenge of delivering high-quality data that answers meaningful questions, Mellion is dedicated to “incorporating the patient’s voice into everything we do.”
This means ensuring input from preclinical scientists, key opinion leaders and patients “even before the first patient is enrolled in a clinical trial,” she told BioSpace.
Prior to entering the pharmaceutical industry, Mellion maintained an active clinical practice and conducted grant-funded research in neuropathic pain that examined the effects of alcohol on the peripheral nerves.
She became involved in medical education at Brown University’s Warren Alpert Medical School (in Providence, Rhode Island) as the residency director and director of the clinical neurophysiology fellowship for the neurology program.
A Desire to do More
Mellion’s desire to make more meaningful improvements in patients’ lives led her to explore an industry career.
“I was very interested at the time in learning to conduct clinical trials that matter to patients,” she shared. Her goal was to learn, at a deep level, how the industry advanced next-generation technologies and medicines to the clinic.
In 2015, Mellion transitioned into the pharmaceutical industry to deepen her understanding and experience in order to advance meaningful therapies for patients living with diseases that otherwise have no other treatment.
She held leadership roles at Vertex and Biogen, before becoming executive medical director at Fulcrum Therapeutics. There, she led the development team from early to late phase clinical trials for a novel treatment for facioscapulohumeral muscular dystrophy (FSHD).
In April she joined PepGen, which is developing an enhanced delivery oligonucleotide (EDO) therapy for Duchenne muscular dystrophy (DMD). The asset is currently in Phase I clinical trials.
The trial, which involves healthy volunteers, will advance to EDO therapies in patients living with DMD and myotonic dystrophy type 1 (DM1) next year.
“We know that oligonucleotides are effective in modulating gene expression,” Mellion said. “The challenge has been delivery of clinically meaningful concentrations of these oligonucleotides to affected tissues.”
PepGen’s EDO technology conjugates a proprietary delivery-enhancing peptide to therapeutic oligonucleotides. The aim “is to enhance cellular uptake into those hard-to-reach tissues including skeletal and cardiac muscle as well as the central nervous system to effectively treat the underlying cause of these diseases,” she explained.
Combining the Tenets of Academia and Industry
“Part of the reason I chose clinical development is that I found it to be one of the most challenging, and most rewarding, functions at the table,” Mellion shared.
“Developing and executing clinically meaningful clinical trials…really is a team sport.” That collegial collaboration to achieve the best solutions is one aspect of academia that has carried over into industry, she noted.
Another cherished aspect is her interaction with patients.
“Keeping that part of my career active is critical,” Mellion said. “The doctor-patient relationship is special.”
Having specialized in neuromuscular disease and general neurology, many of her patients have long-term problems. “I end up seeing them for a very long time. I’m on this journey with them to find treatments that make their lives better,” she said.
Designing Clinical Trials for Patients
Those interactions, in turn, help her to design clinical trials that are more impactful to patients. In designing clinical trials, it’s important to understand what assessments are meaningful to patients, Mellion said.
“In myotonic dystrophy, we may look at the difficulty patients have opening their hands (myotonia). While many patients don’t find that (inability) especially annoying, there are correlations between their myotonia and muscle strength and fatigue,” she explained. “We would not necessarily have known that had we not talked about it with patients.”
Likewise, among DMD patients, the importance of upper extremity strength to young men and boys was undervalued. Now, she said, “Understanding how our therapies affect their upper extremity function is just as important as how it affects their ambulation, and sometimes even more so.”
Mellion frequently asks her patients, “If you were designing the clinical trial, what would you look at? What should I assess?
“We also tend to underestimate how much patients are willing to do in clinical trials,” she noted. For example, while the assumption may be that patients are only willing to do one or two muscle biopsies, “In working with rare disease populations, we found many patients…were willing to do as many muscle biopsies as needed as long as it provides the data necessary to determine whether this therapy is effective.”
The same is true of tolerability. “Patients often are willing to accept some side effects if they know that a treatment will potentially improve their lives,” Mellion said.
Another important aspect to consider is the burden participation places on patients and their families.
“Many of these patients take time from their lives and their families’ lives to travel to clinical trial sites that are far away, so understanding how to make that experience better for them is very important to us,” Mellion said.
“For our clinical trials we are exploring the potential of implementing technologies such as virtual visits and video assessments, to reduce the time spent in clinics and the burden of multiple clinical assessments, which can be exhausting for both patients and families.”
Success in clinical development to Mellion, “Is not necessarily whether the drug works but whether we gathered high-quality data, and whether we designed the right trial to answer the question we asked.” Often, that relates to efficacy and the degree to which it is meaningful to a specific patient population. “This is another way of contributing to the knowledge within that field.”
