In Clinical Trials: A Potential Self-Administered Treatment for Diabetic Macular Edema

retina with diabetic retinopathy

Aerpio Therapeutics, Inc. is a new Cincinnati, Ohio-based biopharmaceutical company focused on developing new therapies for vascular [i.e., blood vessel] diseases, including diabetic macular edema (DME) and age-related macular degeneration (AMD).

This week, Aerpio announced positive clinical trial results for AKB-9778, which shows potential for self-administered subcutaneous [i.e., beneath-the-skin injection] treatment of DME, offering an alternative to the current treatment standard of EYLEA, Avastin, and Lucentis, administered via eye injection.

The as-yet-unnamed AKB-9778 demonstrated promise in initial trials with laboratory mice, as reported in the September, 2014 edition of The Journal of Clinical Investigation, and subsequently initiated two new human clinical trials: the TIME-1 DME study (completed) and the TIME-2 DME study (in progress).

More about AKB-9778 and Diabetic Macular Edema

From Aerpio Therapeutics Announces Publication of Preclinical Data on AKB-9778 for Common Eye Diseases at BusinessWire:

Aerpio Therapeutics, Inc., announced the publication of preclinical data demonstrating that lead candidate, AKB-9778, reduces abnormal blood vessel growth and leakage in mouse models of ophthalmic diseases, such as diabetic macular edema (DME) and age-related macular degeneration.

These data were published in collaboration with researchers at Johns Hopkins School of Medicine, Max Planck Institute, and Duke University. AKB-9778 is a small molecule activator of Tie2 currently in a Phase 2 clinical study for the treatment of DME.

[Editor’s note: Tie2 plays a central role in blood vessel maturation and maintenance, which prevents the blood vessel leakage that is characteristic of retinal diseases, such as DME.]

“Importantly, the results support the benefit of AKB-9778 as either a mono [i.e., stand-alone] therapy or as an adjunct to anti-VEGF agents [explained below]. Taken together, the results strongly support our ongoing development program in patients with diabetic eye disease and the expansion of the program into other major retinal diseases such as wet age-related macular degeneration and retinal vein occlusion,” said Kevin Peters, MD, Chief Scientific Officer of Aerpio.

“We also showed that AKB-9778 was effective in these models when administered either directly into the eye or when given systemically by subcutaneous [i.e., beneath the skin] injections. Given the high cost and inconvenience of current therapies for retinal disease, which are typically injected directly into a patient’s eye at a physician’s office, we sought to develop AKB-9778 as a potential self-administered subcutaneous alternative that could be used as a mono therapy or potentially [in combination with] anti-VEGF agents.

About Diabetic Macular Edema (DME)

Diabetic macular edema [edema = a swelling or accumulation of fluid] (DME) can occur in people with diabetes when retinal blood vessels begin to leak into the macula, the part of the eye responsible for detailed central vision. These leakages cause the macula to thicken and swell, which, in turn, creates a progressive distortion of central vision.

Although this swelling does not always lead to severe vision loss or blindness, it can cause a significant loss of central, or detail, vision, and is the primary cause of vision loss in people with diabetic retinopathy.

Anti-VEGF Treatments and Diabetic Macular Edema (DME)

Angiogenesis is a term used to describe the growth of new blood vessels and plays a crucial role in the normal development of body organs and tissue. Sometimes, however, excessive and abnormal blood vessel development can occur in diseases such as cancer (tumor growth) and retinal and macular bleeding.

Substances that stop the growth of these excessive blood vessels are called anti-angiogenic (anti=against; angio=vessel; genic=development), and anti-neovascular (anti=against; neo=new; vascular=blood vessels).

The focus of current anti-angiogenic drug treatments is to reduce the level of a particular protein (vascular endothelial growth factor, or VEGF) that stimulates abnormal blood vessel growth in the retina and macula; thus, these drugs are classified as anti-VEGF treatments.

At present, these drugs are administered by injection directly into the eye after the surface has been numbed. Current anti-VEGF drugs in use include EYLEA, Avastin, and Lucentis.

About Clinical Trials

Most clinical trials are designated as Phase 1, 2, or 3, based on the questions the study is seeking to answer:

  • In Phase 1 clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe and effective dosage range, and identify possible side effects.
  • In Phase 2a/2b clinical trials, the study drug or treatment is given to a larger group of people (100-300) to determine if it is effective and to further evaluate its safety.
  • In Phase 3 studies, the study drug or treatment is given to even larger groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
  • In Phase 4 studies, after the Food and Drug Administration (FDA) has approved the drug, continuing studies will determine additional information, such as the drug’s risks, side effects, benefits, and optimal use.

The completed Phase 1b/2a TIME-1 DME Study, entitled Safety and Pilot Efficacy of AKB-9778 in Subjects with Diabetic Macular Edema, evaluated the safety and effectiveness of one month of twice-daily subcutaneous injections of AKB-9778 in 24 subjects with DME. The treatment was well-tolerated and improved visual acuity in some subjects.

The ongoing Phase 2 TIME-DME Study, entitled Safety and Efficacy of AKB-9778 as Monotherapy or Adjunctive to Ranibizumab Compared to Ranibizumab Monotherapy in Subjects with Diabetic Macular Edema, will evaluate the safety and effectiveness of AKB-9778 alone and in combination with ranibizumab [i.e., Lucentis] for three months in subjects with DME.

Additional Information

From Aerpio Therapeutics at the ARVO Annual Meeting, via an Aerpio news release:

“Alternative therapies are needed for treating patients with DME who have persistent macular edema and vision loss despite frequent anti-VEGF injections and also for patients who don’t want or don’t tolerate intravitreal injections,” said Jeffrey Heier, MD, Ophthalmic Consultants of Boston.

“Based on these early clinical data, AKB-9778 may provide a patient self-administered alternative that could be helpful in the treatment of diabetic macular edema.”

VisionAware will continue to report the results of this ongoing, yet still unproven, research as they become available.