A conversation with Ching Yu Christina Wen, MD, Chief Medical Officer at Pellage Pharmaceuticals
Approximately 50 percent of men and women suffer from male pattern baldness, or androgenetic alopecia. There are many different types of alopecia, including chemotherapy-induced alopecia and autoimmune alopecia such as alopecia areata, but male pattern baldness is by far the most common, and most people will experience it in their lifetime, says Qing Yu Christina Weng, MD, CMO of Perage Pharmaceuticals.
Wen and his team at Pelage are embarking on a Phase 2a clinical trial of PP405 as a treatment for male pattern baldness.
In this interview, Wen talks about Pelague’s desire to buck existing trends in hair loss treatment, expand studies to include patients with all skin and hair types, and incorporate an element of decentralization into the trial design.
We explore the current state of male pattern baldness, first detailing the patient population affected and its impact, and then assessing the currently available treatments. What’s missing in terms of treatment options?
Although male pattern baldness affects all genders, the symptoms of hair loss differ between men and women. In men, hair loss mainly affects the frontal hairline and scalp at the top, while in women, the most common sign is a widening part. This is of course a generalization, and both men and women with male pattern baldness will also experience generalized hair thinning.
Hair follicles normally cycle through periods of resting (telogen) and anagen (growth) phases. This cycle can be disrupted by a variety of factors, including age, hormones, stress, and genetics, which can cause the stem cells in hair follicles that initiate new hair growth cycles to go dormant over time.
While current treatments can slow the progression of hair loss, most target secondary factors such as hormones. There are only two FDA-approved drugs for the treatment of male pattern baldness: finasteride and minoxidil, and no new drugs have been approved in the past 20 years. Both have limited effectiveness and only a small proportion of users experience improved hair growth. Additionally, hormonal therapies such as finasteride have significant side effects.
Other treatments for male pattern baldness include over-the-counter supplements, red light therapy, platelet-rich plasma injections, and hair transplants. These are costly, time-consuming, have limited effectiveness, and most have not been tested in rigorous clinical trials.
Due to the shortcomings of current hair loss treatments, Pelage’s collaborating scientists set out to develop a new treatment option based on strong science that directly targets hair follicle stem cells. This investigational, hormone-free treatment is designed to be non-invasive and is suitable for all genders, hair and skin types.
What hope does PP405 bring to patients?
PP405 aims to provide a non-invasive, topical hair loss solution based on stem cell biology that is suitable for all genders, skin types, and hair colors and textures. Unlike existing treatments that target the indirect causes of hair loss, PP405 is designed to reactivate dormant hair follicle stem cells that may remain in the resting phase, initiating a new hair growth cycle.
Due to its mechanism of action, this approach is expected to be effective for both men and women, and for all hair and skin types.
Pelage has just started dosing patients with PP405 in a Phase 2a study to confirm safety and preliminary efficacy. With regards to enrollment, what has been the response and willingness of patients with male pattern baldness to participate?
“We are pleased to see such strong interest from individuals interested in participating even before our Phase 2a study has begun, reflecting both how prevalent male pattern baldness is and the excitement surrounding our new mechanism of action. We are currently actively enrolling participants across the United States.”
Specifically, the study has inclusion/exclusion criteria that welcome participants of both genders and of various skin tones and hair types. Has this always been the case with studies looking for treatments for alopecia?
Unfortunately, alopecia clinical trials do not always include all genders or skin pigment types. This reflects several factors, including the treatment mechanism and the technology used to assess the endpoints. For hormonally active agents such as finasteride, many women may not be eligible due to hormonal effects and the risk of birth defects, which automatically limits the population that can be enrolled. Additionally, high-resolution imaging technologies used to assess hair count as a clinical trial endpoint have evolved significantly. Historically, darker hairs against lighter skin were easier to image and assess, limiting the inclusion of darkly pigmented skin in clinical trials. Thanks to continued innovation in this field, we are fortunate to have imaging technologies available that can quantify hair density and other objective measures across all hair types and skin pigment types. We are aware of the existing limitations of imaging technology and discussed early with our imaging provider to ensure that this capability was built in from the beginning of our Phase 2a study to allow adults of all genders, hair types, and skin types to participate.
So why is it important to include patients of diverse genders and races in such studies? What do we know about different skin tones and hair types as they relate to alopecia? Are there differences in the prevalence or symptoms of the disease?
We know that hair loss, in this case male pattern baldness, can happen to anyone regardless of gender, hair type or skin color. Fortunately, we have a potential treatment that directly targets the cause of hair loss at the level of hair follicle stem cells. Disruption of the natural hair cycle is common to all patients with male pattern baldness, regardless of gender or race. The factors that cause this disruption can be multifactorial, including age, stress, hormones, genetics, nutrition, environmental factors and even hairstyle. These factors vary from patient to patient, but we can work around them and intervene at the level of hair follicle stem cells. We are conscious of this unique opportunity to help patients of all genders, hair types and skin types through a common mechanistic pathway, and we are designing our trials from the beginning to reflect the diversity of our treatment audience.
And what are the risks if a more diverse group of patients is not included?
Designing clinical trials with diverse populations in mind is critical. The sooner we can enroll diverse patients, the more data we have on the safety, tolerability, and effectiveness of a particular treatment for all people. This ultimately impacts the populations for which a drug is approved and how it is used commercially, so it is in the interest of both patients and drug developers to enroll diverse populations as soon as possible.
Dermatology clinical trials can require frequent in-person consultations. How did you structure this trial’s mix of in-person and digital/remote elements to engage with patients?
PP405 is a non-invasive topical medication designed to be applied by the patient. Patients participating in our clinical trial will be able to store and apply the treatment at home. As with most clinical trials, you will be required to come into the clinic at scheduled times for monitoring visits that include assessment of safety and efficacy endpoints. However, for the majority of trials, patients will be able to perform the procedure at home.
Given the prevalence of male pattern baldness, are there many competing trials for the treatment, and if so, what are some of the strategies Pelage has used to increase awareness of PP405 among HCPs and patients?
This field is primarily experiencing incremental innovation. The majority of treatments in development, including pre-clinical assets and those in Phase 1 and beyond, still use older mechanisms of action and the market is dominated by reformulations and copycat products. We believe that PP405’s novel mechanism of directly targeting hair follicle stem cells, combined with a local delivery approach, is unique and fills a significant unmet need in the current therapeutic market for a safe, effective non-invasive product. This mechanism is also supported by translational and clinical data from in vitro facelift skin studies and our Phase 1 clinical trial.
The data, presented during a late-breaking session at the American Academy of Dermatology (AAD) 2024 Meeting, provided mechanistic evidence for PP405 that is consistent with the preclinical data. The company’s co-founders, William Lawrie, Professor of Molecular, Cellular and Developmental Biology, Heather Kristofk, Professor of Biochemistry, and Michael Jung, Distinguished Professor of Chemistry, have also published extensively in the area.
Through publication in a peer-reviewed journal and presentation of the data at conferences to clinical and scientific colleagues, we are able to highlight this positive early-stage data, share plans for continuing our clinical trials, and highlight the unique potential of PP405 to reverse the effects of hair loss for countless patients with male pattern baldness.
About the experts:
Qing Yu Christina Weng, MD, is Chief Medical Officer of Pelage Pharmaceuticals. Weng is a physician-scientist-entrepreneur, a board-certified dermatologist, and a member of the faculty at Harvard Medical School. She has experience in corporate startup strategy as Head of Business Development and Strategy at Kira Pharma and CSO and co-founder of Mymiel Skincare. She serves on the advisory board of Immunis, a regenerative medicine company developing secretome for age-related dysfunction. She serves on the board of directors of the Dermatology Innovation Forum and the Dermatology Summit. Weng received her undergraduate degree from California Institute of Technology and her MD from Harvard University, where she completed her residency and fellowship in dermatology.
