Developing bold medicines to preserve vision and transform the treatment landscape for DME

My training as a clinical ophthalmologist and retinal surgeon led me to a career dedicated to developing better therapies for people suffering from debilitating eye diseases and the many consequences of vision loss.

Eye disease impacts much more than vision: it changes lives and takes a toll on the ability to work, stay productive and active, and remain strongly connected with family and community. Diabetic macular edema (DME), the leading cause of blindness in the US among working-aged adults, is a disease with increasing incidence and impacts that go beyond patients’ health, generating significant financial and care delivery costs for the healthcare system and society. New and better treatment options are desperately needed that serve patients better and reduce the tremendous systemic burden of DME.

Diabetic eye disease

In the last 20 years, the incidence of adults diagnosed with type 2 diabetes has more than doubled, and the complications related to this diagnosis are also on the rise. One of these complications is diabetic retinopathy (DR), which is often unnoticeable in its early stages. DR affects approximately one-third of adults with diabetes and is the leading cause of vision loss in the working-age population between 20 and 65.

In DR, the high blood sugar levels associated with diabetes can damage the retina’s blood vessels, leading to fluid and blood leakage into the macula. The macula is the central part of the retina responsible for high-resolution vision. When fluid accumulates in the macula, it causes swelling and thickening, leading to DME, a severe vision-threatening complication of DR.

DME can affect individuals with both type 1 and type 2 diabetes. The risk of developing DME increases with the duration and severity of diabetes. Early detection and regular eye examinations by an ophthalmologist or retina specialist are crucial for individuals with diabetes to monitor, manage, and treat diabetic eye disease.

A treatment landscape with unmet need

Currently, there are over 750,000 DME patients in the US and 21 million worldwide - and most of these patients are treated with anti-vascular growth factor (anti-VEGF) inhibitors delivered by monthly or bi-monthly injections directly into the eye over long periods of time to preserve vision. Anti-VEGF treatments are a class of medications used to treat a variety of eye conditions, including DME, that target the vascular endothelial growth factor- a protein that plays a significant role in developing and maintaining blood vessels. In DME, VEGF is overproduced, leading to the abnormal growth of blood vessels and increased vascular permeability, contributing to macular edema.

Regular anti-VEGF injections are typically required to maintain the treatment effect, and patients are required to return to the clinic to have their ophthalmologist or retinal surgeon assess the progression of disease. Frequency of injections varies depending on the specific medication used, the severity of DME, and individual patient response. Patients may initially receive monthly injections, followed by maintenance therapy, which may require injections every month or bi-monthly. In most cases, as patients are often not able to see or have compromised vision, they are very dependent on caregivers to get them their appointment and for aftercare support.

Due to their invasive route of anti-VEGF administration requiring a consistent regimen of eye injections, which can come with the occasional serious side effects, there is a tendency to delay treatment. As a result, retina specialists prefer to wait until the disease has progressed, while patients often struggle with long-term compliance. This treatment paradigm, which is the current standard of care, is both burdensome and ineffective over time for nearly half of all patients. The result is undertreatment and suboptimal vision outcomes for DME patients.

Reducing invasiveness, improving vision prospects

Patients deserve new treatment options for preserving their vision, and the field of ophthalmology recognises that a treatment paradigm shift is needed that advances novel therapeutic approaches to address DME. Rezolute is driven by this need, which is why it is developing a less invasive and potentially more effective treatment for DME patients.

Progressing a novel, small molecule oral therapy for the treatment of DME- which can potentially eliminate the need for intra-ocular injections - RZ402 is a selective and potent plasma kallikrein inhibitor (PKI), an approach with the possibility to halt vision loss. By inhibiting the formation of kallikrein, RZ402 is designed to block downstream bradykinin production and the pro-inflammatory, pro-coagulant, and fluid-leakage contact-activation cascade.

By providing a new, more convenient and less invasive treatment option that can be taken at home and does not require administration by a retinal surgeon, patients can initiate therapy sooner and more easily adhere to prescribed treatment guidelines. This approach represents a better opportunity for preserving vision than the current standard of care, and meaningful improvement of treatment can also restore the ability for people to continue working and remain connected to families, communities, and society as a whole.