Pathways for Rare and Orphan Solutions ("PROS")

Pathways for Rare and Orphan Solutions  ("PROS Foundation")

1. Helping patients in Sub-Saharan Africa obtain care for their rare craniofacial conditions.

In many areas of Sub-Saharan Africa, people with physical or intellectual disabilities are stigmatized, fueled by beliefs that they are cursed, possessed, or their condition is caused by sin. Disabled children are social outcasts, likely to be denied healthcare, unable to attend school, and at higher risk of abuse and sexual violence. These children are often hidden away, out of sight, or worse. One such class of rare disorders is craniofacial abnormalities such as cleft palate, but especially rare syndromic craniosynostosis. Craniosynostosis is a birth defect in which the bones in a baby’s skull join together too early, affecting the shape of the head and face. Examples include Apert, Pfeiffer, and Crouzon syndromes – all caused by mutations in FGFR1-2 genes, and Treacher Collins Syndrome, caused by variants in TCOF1, POLR1C or POLR1D. Respiration, hearing, vision, and sometimes neurodevelopment can all be affected, and most certainly, appearance. Many individuals have life-threatening complications, including airway and central nervous system compromise, leading to early death without proper medical and surgical management. Even in the US, these children live a childhood filled with medical emergencies, unwanted stares, bullying, and 6-50 surgeries before reaching adulthood. Children in LMICs where there are no specialized capacity often die early or are isolated, while in other cases, they may be “sacrificed” by parents who think they are cursed. The estimated prevalence of these syndromes in Sub-Saharan Africa is 810 million. However, with proper surgical intervention, individuals can live normal adult lives. The hope is that one day there will be a drug treatment that could minimize the need for surgeries, but this is not likely for at least 7 years since there are none that are close to clinical trials.  

Complex craniofacial surgery other than for cleft lip and palate is practiced mainly in the advanced countries of Europe and North America. Treating patients with these rare syndromic craniofacial conditions requires an interdisciplinary team, including a plastic surgeon, neurosurgeon, ophthalmologist, otolaryngologist, and more. Early diagnosis and appropriate medical care are crucial for the survival of individuals with these conditions, but few patients in Africa have access to either. The main reasons for this include the lack of care centers with the necessary expertise and equipment and financial reasons. There is typically no reimbursement for these procedures, and most patients cannot afford to pay out of pocket. It is incredibly sad to see patients stigmatized, suffering and losing their lives for financial reasons. 

2. Developing clinical trial capabilities for rare diseases in Africa 

The conduct of high-quality clinical trials in low—and middle-income countries (LMICs) is vital for providing equitable access to healthcare innovations and ensuring that products, technologies, and practices are safe and effective in LMICs’ diverse populations. However, few healthcare facilities have experience conducting clinical trials, too few African patients have received diagnoses for their rare conditions, and African patients are significantly underrepresented in clinical trials.

1. Building capabilities for treating complex craniofacial conditions in Africa

Dr. Obiri-Yeboah is one of the very few craniofacial surgeons in Africa. He completed training at the U. of Alabama nine years ago and is working to build a Craniofacial Center at the Komfo Anokye Teaching Hospital in Ghana. PROS is endeavoring to support him by:

• Coordinating continued education
• Acquisition of state of the art imaging and surgical technology and intensive care resources
• Fnancial support for patient surgeries.

Dr. Obiri-Yeboah hopes to continue his training in the US and subsequently share his expertise with other doctors in Africa, beginning with Nigeria and Liberia, so that they can establish additional centers. 

Based on our 4 years of experience working with a US organization called Born a Hero, PROS has become knowledgeable about rare syndromic craniosynostosis. We have built a Centers of Excellence network of the top US institutions treating patients with these disorders which PROS is leveraging to support Dr. Obiri-Yeboah. The US institutions currently engaging in this effort include CHOP, CHLA, and Boston Children’s. We are developing opportunities for Dr. Obiri-Yeboah to receive ongoing education at one or more of these three US institutions so he can provide better treatment to patients and also train others in Africa. PROS is also raising funds to help purchase equipment and support surgeries and care costs. 

2. Encouraging clinical trials for rare diseases

Some rare patients may benefit from participating in a clinical trial if treatments are unavailable, especially if an expanded access program is planned upon trial completion. Connected to the craniofacial initiative as a resource is building a Clinical Research Organization in Africa focused on rare diseases.  

PROS has introduced free genetic testing resources to several groups in Africa, and as a result, several hundred patients have been diagnosed. We are promoting the use of Facial Recognition/AI tools to inform geneticists in making a diagnosis and have also developed a patient registry to gather information from physicians and patients, which we plan to roll out via patient groups in Namibia, Rwanda, and South Africa.

PROS is helping to establish a new Clinical Research Organization based in Ghana called Optima Clinical. Optima is led by a Ghana native with over 15 years of rare disease experience in US pharmaceutical companies. The hope is that the patient registry “locator” coupled with this CRO, will encourage more companies to consider Africa for rare disease clinical trial recruitment, potentially helping patients and, at the same time, increasing trial diversity. PROS will reach out to companies with development programs matching diagnosed patients. 

Our solution serves neglected Sub-Saharan African patients who are living with rare diseases, with our biggest impact on patients with rare craniofacial disorders in West Africa. With continued education, adequate equipment, and financial support, Dr. Obiri-Yeboah’s clinic alone could help more than 100 patients annually, including at least ten rare syndromic patients. That number could be multiplied by the number of other doctors he trains, but it also depends on the financial support PROS and others can provide. With some conditions, a single surgery can completely correct a child’s condition, resulting in acceptance and the end of isolation so the child can have an improved quality of life. For the syndromic patients, actual lives will be saved since many of these patients can not survive without surgeries or will live with permanent damage to the brain, vision, hearing, and more. We also plan to provide some mental health and emotional support to patients and their families by connecting them to organizations in the US, including the Children’s Craniofacial Association (CCA Kids), Born a Hero, and Headlines in the UK, and in some cases with “buddies” all of whom can provide emotional support to help them cope with being different and the surgeries they face.

Optima Clinical is an African CRO that will primarily benefit African residents—both patients and employees. The company will bring rare disease clinical trials to patients who have no other treatment options and provide local Africans with training and jobs. At least two drug therapies are in pre-clinical development for FGFR-associated craniosynostosis syndromes that will minimize the need for so many surgeries. Trials for treatments such as this could be opportunities for patients as long as the ethics of treating disadvantaged populations are kept at the forefront.

 As a small organization, we certainly can’t save the world, but even if we help just a handful of patients each year to live healthier and happier lives, we will consider our efforts successful.  

For more than four years, PROS has worked as part of the US-based Born a Hero Research Foundation, supporting patients with rare syndromic FGFR-related craniosynostosis in the US. Through this work, PROS has helped organize and conduct annual conferences, launched and supports a patient registry, connected with drug developers, and developed a network of Centers of Excellence through which collaboration to improve patient care is underway. We are currently working with several of these institutions to form a rare disease consortium to study syndromic craniosynostosis.

Born a Hero has developed several resources for families such as Pre-Op and Post-Op tips for kids undergoing reconstructive surgery, dietary plans, a list of resources such as free Apps, 1 pager for schools, and has created a curriculum that can be presented at schools to help break barriers between kids and their peers by encouraging healthy conversations in the classrooms. Born a Hero has a private Facebook Group that specifically supports the FGFR community through education and opportunities, which includes 770 members. We also partner with the Children’s Craniofacial Association which supports families with any craniofacial condition through education, financial support, and by hosting a yearly family retreat

PROS is now expanding its support of rare syndromic craniosynostosis to Sub-Saharan Africa, which presents new challenges. Collaboration among the surgeons in Ghana with the US Centers of Excellence is in the early stages. 

Optima Clinical, a rare disease CRO that will eventually provide financial support to rare craniosynostosis patients, has been founded and is in the start-up phase. 

1. African Craniofacial Capabilities

Except for the center that Dr. Obiri-Yeboah is building, no known craniofacial centers in West Africa can care for patients with complex craniosynostosis syndromes. A few organizations, such as Operation Smile, address relatively simple craniofacial disorders such as cleft palate, but they cannot tackle the disorders that require ongoing surgeries and care needed to treat the syndromes. Likewise, some doctors may do missionary work to perform surgeries from time to time, but these syndromic patients need ongoing care management. By partnering with the top craniofacial institutions in the US that share advancements in treatment protocols, Dr. Obiri-Yeboah can apply the same innovative techniques as in the US. One example of this under discussion with the Craniofacial Centers of Excellence Network is new non-invasive techniques for monitoring the visual pathway function via surrogate biomarkers to assess raised intracranial pressure that can cause brain damage and blindness. Acquisition of new technology will be needed. 

2. Promoting Facial Recognition as a first step in diagnosis.

We are introducing our African colleagues to free tools that aid in rare disease diagnosis by collecting history and symptoms together with photos and videos. Companies such as FDNA have tools that caregivers and physicians can use to hone in on a disease using databases of genetically relevant phenotypic information. This information can then determine the panels to be ordered and correlate with variants to provide a diagnosis. This is especially useful for craniofacial disorders and will contribute to understanding the genotype-to-phenotype relationships in these rare patients. 

3. Clinical Trials

Of the approximately 118 clinical trials currently recruiting or planned in Sub-Saharan Africa, only 2 are for rare diseases, and pharmaceutical companies sponsor none. Reasons for this may include the absence of information about where to find the patients, the lack of rare disease experience to run the trials, the lack of qualified sites, and the inability of patients to travel to sites from remote areas. Optima Clinical and PROS are addressing these issues.

 Patient recruitment for clinical trials for rare diseases is challenging, especially for ultra-rare genetic diseases. For some indications, sponsors may open a site for just a handful of patients. At this time, most sponsors are not aware of the rare genetic diseases in Africa (which may be more prevalent than in other parts of the world) because few patients have been diagnosed. More African patients are being diagnosed thanks to several free genetic testing services. PROS plans to capture some of this information in the registry database in numerous countries and make portions of the de-identified data available for clinical trial sponsors to help locate patients. No such database exists at this time. The registry has been developed but is undergoing enhancements before launch. 

 Since travel can be difficult in Africa, Optima Clinical will use a technology platform and processes to facilitate decentralized trials paired with software that allows offline data capture when internet service is unavailable. 

1. To raise awareness about rare craniofacial conditions
2. To raise money to support initial equipment purchases, patient surgeries and patient travel in Africa
3. To get support with lessening the stigma associated with craniofacial conditions in Africa

PROS has assembled a diverse team of individuals in the US and various African countries working together to help rare disease patients in Africa. Each individual brings a different perspective to the project, including craniofacial experience and direct experience working in and with patients in Africa and other LMICs.

Ellen Morgan, the Founder and President of Pathways for Rare and Orphan Solutions (PROS), is passionate about helping underserved patients. Although based in the US, she has considerable African experience. In 2011, she started a non-profit organization to run clinical trials for neglected diseases and provide clinical research training in several African countries. In addition, Ellen founded and led two successful CROs, Synteract and Agility Clinical (rare disease focus), which were both acquired. Ellen started the PROS Foundation in 2017 to support rare disease patient organizations. The organization has worked with numerous rare disease patient organizations over the years, including several in Africa. During her career, Ellen has received numerous awards for leadership and entrepreneurship.  Ellen has been working with the Born a Hero Research Foundation since 2020 becoming very knowledgable about rare syndromic craniosynostosis. 

Craniofacial Center Project

Solomon Obiri-Yeboah is a Cranio-Maxillofacial Surgeon, at the Komfo Anokye Teaching Hospital, Kumasi, GHANA. He has been performing craniofacial sugeries in Ghana for 8 years and is the lead surgeon for the Craniofacial Center Project in West Africa. 

Jesse Taylor, MD, Co-Director of the Craniofacial Program at the Children's Hospital of Philadelphia is one of the most recognized craniofacial surgeons in the US. He has served on international surgical mission trips to developing countries and is enthusiastic about using his expertise to support and guide Dr. Obiri-Yeboah. 

Mark Urata, MD, DDS is the Division Head; Chief, Division of Plastic and Maxillofacial Surgery, Keck School of Medicine of USC. He is the Principal investigator of the International Craniofacial Children's Fund (ICCF) enabling children with severe craniofacial abnormalities from medically underserved countries to benefit from care they might otherwise be unable to receive. He is the co-principal investigator of the Teledentistry/Telecraniofacial Program, designed to use state-of-the-art technology to deliver services to underserved populations. 

Carolina Sommer is the Founder of Born a Hero and mother of a child with Pfeiffer Syndrome, a rare syndromic craniosynostosis.

Diagnosis in Africa 

Bianca Özcan is the Founder of Namibia Alliance for Rare Diseases (NARD). She is working with PROS to facilitate diagnoses and treatment of patients in Namibia.

Manzi Ndamukunze is Center-Alliance, Rwanda's Founder and managing director, and the father of a rare disease child. 

Rare Disease Clinical Trials in Africa 

Yaw Asare-Aboagye, Founder and President of Optima Clinical, GHANA. Yaw returned to his native Ghana in 2019 after 15 years in rare disease clinical trials in US pharmaceutical companies. Most recently he established clinical research capabilities for DNDi in Kenya. Yaw is passionate about helping rare disease patients, especially on his home continent. 

Watiri Kamau-Kelley is a native of Kenya with Clinical Affairs Senior Leadership experience in US pharmaceutical companies. She is supporting PROS with African initiatives. 

• African Craniofacial Centers: Continue to push for collaboration across continents while not allowing busy schedules to halt progress.
• Subsidize the cost of advanced imaging and surgical support technology  surgeries for up to 10 patients per year.
• Introduce craniofacial patients to communities, especially CCA kids, Born a Hero, and Headlines UK.
• Support the travel of 1-5 African patients and their families to the annual CCA kids retreat. CCA’s Annual Family Retreat & Educational Symposium provides individuals affected by a facial difference and their siblings and parents an opportunity to interact with others who have endured similar experiences. The unique format of the Retreat allows families to share ideas, problems, and solutions and make life-long friendships. These kids deserve the same chances in life as anyone else.
• Facilitate diagnosis—The goal is to double the number of patients diagnosed in Africa each year.

• Bring at least 2 new rare disease clinical trials to Africa annually, and generate revenue to support the Craniofacial Center. 

Craniofacial Center –We Will Save Lives

The "Elevator Pitch" video link below provides some information about Apert Syndrome, one of the rare craniosynostosis syndromes that will be treated in the Craniofacial Center in Ghana. Patients with rare craniosynostosis syndromes can thrive with the right care but may fail to survive without it. Of the 2 patients diagnosed via WGS over the last 2 years with Pfeiffer Syndrome, one has already passed away. 

Our specific actions include:

• Arrange for Dr. Obiri-Yeboah to receive up-to-date and ongoing educational support from US Institutions.
• Spread information about craniofacial deformities so that they become better understood and people who have stayed hidden will be more open to receiving treatment. In addition to expertise and cost, one of the barriers to treating craniofacial deformities in Africa is the perceived stigma associated with them. The Craniofacial and Neurosurgery Department at KATH (Komfo Anokye Teaching Hospital, Kumasi, Ghana) is forming a link with the local newspaper, the most authoritative and widely read newspaper in Ghana.
• Raise funds to upgrade the facility’s equipment and technology and to subsidize each complex patient who requires MRIs and/or CTs and multiple surgeries. By Year 2, Dr. Obiri-Yeboah’s clinic may be able to treat 15-20 complex cases annually. Treating one complex case in Ghana costs approximately $6,000-$10,000 USD per year. PROS aims to raise funding to subsidize equipment purchases and surgeries for as many patients as possible.
• Through Dr. Obiri-Yeboah’s work and efforts to train other surgeons in Africa, we estimate that more than 30 complex patients who might otherwise not survive can be treated by Year 3, with an increase in each subsequent year.

Diagnosis, Patient Registry and Access to Treatment

• Facilitate the diagnosis of at least 100 patients per year via facial recognition / AI coupled with genetic sequencing
• Introduce diagnosed patients to patient organization and/ or buddy to help with support
• Patients may be able to receive treatments through a humanitarian program or enroll in a clinical trial.

 Rare Disease Clinical Trials in Africa

• Attract at least 2 additional rare disease clinical trials to Africa each year, which could potentially benefit many rare disease patients.
• Hire 5+ new personnel annually, providing jobs to more Africans each year.
• A significant portion of the profits will support craniofacial patients. 

3 full time

6 part-time 

4 years

The team includes an equal mix of American, white men/women and African men/women

Key Resources:

• Grants and Donors
• Revenue Sharing from Optima Clinical
• Training support - Children’s Hospital of Philadelphia,  Children’s Hospital of Los Angeles and  Boston Children’s Hospital

Partners & Key Stakeholders

• Children’s Hospital of Philadelphia
• Children’s Hospital of Los Angeles
• Boston Children’s Hospital
• Komfo Anokye Teaching Hospital in Kumasi
• Optima Clinical

Cost Structure

• The biggest expenditures will be the support of patient surgeries
• Initial investment in Optima Clinical
• Expenditures for equipment and supplies

Key Activities

• Coordination of training programs for surgeons
• Set up of application process for patients in need of funding for treatments
• Set up of application process for patients to attend CCA Kids
• Set up of financial structure
• Business development activities for Optima Clinical

Type of Intervention

• Meetings of craniofacial experts
• Travel arrangements for physician education and patients

Channels

• Local newspapers in African countries
• Physicians

Optima Clinical Profits

• Fund patient procedures and care
• Employee compensation

Segments

• Patients with rare craniosynostosis syndromes are the primary beneficiaries
• Year 1: $12K USD for possible travel expenses for physicians and up to $75K USD for equipment
• Year 2: $70-$105K USD to support patients
• Year 3: $105-$150K USD to support patients
• 20-25 rare craniosynostosis patients receiving care in first 3 years

Funding Needed

Impact

At least 20-25 rare craniosynostosis patients receiving care in first 3 years

PROS has raised $595K previously from donors, patient registry coordination services for rare disease organizations, and clinical research consulting services.  At this time, all PROS personnel are volunteers, so expenses have primarily included education, travel and IT infrastructure. Additional expenses in the future will be the funding of equipment, surgeries and treatments for patients in Africa, and Optima Clinical personnel and operational expenses.

Funding Plans:

• PROS needs immediate funding for the Craniofacial Center training and equipment purchases. In the long term, Optima Clinical will be the primary source of funding. PROS investment costs for the CRO are estimated at approximately $50K USD, but it is expected to be slightly profitable by the end of Year 1.
• Patient Recruitment Revenues – As the “patient locator” accumulates more genetic data, study sponsors may be charged a fee for patient referrals.
• Annual FGFR Syndromes Conference (for rare craniosynostosis syndromes)—Born a Hero has been holding a conference annually since 2019. The conference includes clinicians, researchers, and patient families. Funding is generated from biopharma conference sponsors. Born a Hero has agreed to designate a portion of the conference revenues to fund patient surgeries in Africa.
• Donations and fundraising events – PROS will continue to hold fundraising events such as dinners and auctions.
• PROS will continue to generate revenues via patient registry coordination services. 

Many companies and CROs are sourcing personnel from India and other low-cost countries to supplement their staff and help avoid over-escalation rates. The initial services offered by Optima Clinical in Ghana will be Data Management and Biostatistics, which will be staffed with natives of Ghana, focusing on quality, flexibility, and responsiveness. Optima Clinical will offer rates to clients that are approximately 20-25% less than other CROs and even less than Indian CROs to attract clients, but with the lower personnel costs, profitability will be greater than the industry standard for large US or European-based CROs. Once profitable, Optima Clinical will dedicate ~40% of its profits to funding treatments for rare disease patients in Africa. While not all CROs are successful, there is a high likelihood that Optima Clinical will be successful and profitable, based on the CRO track record and industry experience of the Founders.