The Rezolute team is dedicated to supporting the rare disease communities impacted by frequent hypoglycemia (low blood glucose) due to hyperinsulinism. In addition to furthering the development of RZ358, we work closely with patient advocacy organizations around the world to support family programs, patient-focused research and rare disease awareness activities. Our team understands the value of direct and meaningful involvement with advocates and members of the rare disease communities whose voices serve as a guiding light to our daily work.
Hyperinsulinism (abnormal elevations in the release of the pancreatic hormone insulin) can lead to severe hypoglycemia putting those affected at risk for brain damage and even death. When the body is working properly, the daily control of insulin secretion is highly regulated to prevent hypoglycemia. Too much insulin results in hyperinsulinemic hypoglycemia, characteristic of diseases such as congenital hyperinsulinism (HI), post-gastric bypass hypoglycemia (PGBH) and several other rare conditions noted below.
Congenital HI is the most common cause of recurrent hypoglycemia in neonates and infants. The incidence of CHI is estimated at 1/20,000 live births in the general population, but in certain populations such as in some Arabic and Ashkenazi Jewish groups, the incidence may be as high as 1/2,500. Congenital HI presents in neonates and infants as hypoglycemic episodes, with about 60% of infants with congenital HI experiencing a hypoglycemic episode within the first month of life. These episodes can result in significant brain injury and death if not recognized and managed appropriately. Recurrent hypoglycemic episodes and/or dangerously low blood sugars lead to progressive and irreversible damage over time, including serious and devastating brain and developmental problems. Although most patients with congenital HI can survive into adulthood, the damage from hypoglycemia can affect day-to-day functioning, with lasting symptoms such as seizures, developmental delay, and persistent feeding problems. To date, 14 genes have been found to be the cause of congenital HI. However, one-third or more of patients with congenital HI have an unknown genetic cause. The two most commonly used long-term medications, diazoxide and octreotide, are not Food and Drug Administration (FDA) approved for all forms of this condition and often are ineffective or have intolerable side effects. In cases of congenital HI that are unresponsive to medical management, surgical removal of a portion or the entire pancreas is required. In those with focal congenital HI where a small portion of the pancreas is affected, surgical removal of the specific affected area often results in a cure. In those with diffuse congenital HI where the whole pancreas is affected, a near-total pancreatectomy is undertaken, but still about half of these children will continue to have hypoglycemia and require medical treatment for congenital HI.
The incidence of post-gastric bypass hypoglycemia ranges broadly from an early report of 0.2% to a more recent study of non-diabetic Roux-en-Y gastric bypass patients, demonstrating a 5-year incidence of hypoglycemia of 13%. Although hypoglycemia after bariatric surgery is associated with hyperinsulinemic responses to meals, the cause may be multifactorial. Hypotheses regarding the mechanisms by which hypoglycemia arises after gastric bypass range from beta-cell expansion to altered beta-cell function as well as non-beta cell factors such as glucagon-like peptide 1 (GLP-1). Postprandial hypoglycemia can develop months to years after surgery and occurs with a range of severity in post-gastric-bypass patients. The hypoglycemia associated with bariatric surgery, especially Roux-en-Y gastric bypass surgery, can occur quickly and result in seizures, confusion, and focal neurological deficits. The hypoglycemia after gastric bypass surgery responds variably to nutritional changes and often requires treatment with medication. Current treatment options include acarbose, somatostatin (octreotide), verapamil, and diazoxide, each having the risk of undesirable side effects. In more severe cases, a partial pancreatectomy or reversal of the gastric bypass may be required.
Davelyn brings to Rezolute several key elements in her background that make her uniquely qualified to lead the scientific and patient relations work for the Rezolute team. First and foremost, she is a rare disease parent knowing firsthand the challenges parents and patients face navigating daily life with a difficult and life-threatening disease. Having a child born with congenital hyperinsulinism over twenty-years ago, Davelyn turned that life experience into action by volunteering with the patient advocacy group, Congenital Hyperinsulinism International. While there, she served on the Board of Directors for nearly nine years, seven of those as the Board President. Davelyn was also the Principal Investigator of the Congenital Hyperinsulinism International HI Global Registry, a patient-driven natural history registry, where she worked alongside key HI community stakeholders of advocates, patients and clinicians to design and launch the program. Underpinning the breadth of experience she brings to her role, she is a board-certified family physician and has worked in a variety of practice, healthcare administration and payer settings.
Whether you have been diagnosed with a condition that leads to frequent hypoglycemia due to elevated insulin levels, or you are a representative of a patient advocacy organization for these conditions, we look forward to connecting with you regarding our RZ358 program.
The organizations below—all founded by parents of children with congenital hyperinsulinism —help connect patients and families living with CHI to education, research, clinical care, support services, and the broader CHI community. These are a just a few of the organizations with whom Rezolute collaborates to inform our daily work.
Are you a non-profit patient advocacy group looking for sponsorship or financial assistance for important patient-facing programs? Rezolute is committed to supporting the mission and programs of HI patient organizations through corporate sponsorships. Click here for inquiries on Rezolute’s corporate sponsorship program.
Compassionate Use, also referred to as an Expanded Access Program, is designed to make an investigational medical product available as early as possible to patients without therapeutic options, because they have exhausted or are not a good candidate for approved therapies and cannot enter a clinical trial. Rezolute is committed to providing RZ358 to patients who have seen benefit in our clinical studies. We are actively working to implement an Expanded Access Program for those with serious or life threatening conditions associated with elevated insulin levels causing frequent low blood sugar levels who lack other therapeutic options.