Applied Genetic Technologies Corporation (Nasdaq: AGTC), a gene therapy company in Florida, has reported encouraging interim six-month data from dose-escalation cohorts of a Phase 1/2 trial in patients with achromatopsia.  According to the sponsor, interim results demonstrated “encouraging signs of biologic activity and a favorable safety profile”.  The study is listed at the US clinical trials database, entitled “Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia” and has the identifier of NCT02599922 at clinical trials.gov, also referred to “ACHMB3 Achromatopsia Phase 1/2 Clinical Trial”, listed at the AGCT company.

Achromatopsia (ACHM) is a rare disorder with an estimated prevalence of 1:30,000, characterized by reduced visual acuity, pendular nystagmus, photophobia, eccentric fixation and reduced or complete lack of colour discrimination.  Best visual acuity varies with severity of the disease; it is 20/200 or less in complete achromatopsia and may be as high as 20/80 in incomplete achromatopsia. The disorder is an inherited condition caused by mutations in one of several genes, with the two most common being mutations in either the CNGB3 or CNGA3 genes.  According to the company, there is no specific treatment for ACHM, “although deep red tinted glasses or contact lenses can reduce symptoms of light sensitivity and daytime blindness”.  Two separate AAV gene therapy product candidates for the two most prevalent forms of ACHM are caused by either a genetic mutation in the CNGB3 or CNGA3 genes. Two genetic mutations account for up to 75% of the ACHM patient population.  AGTC’s ACHM programs are designed to provide a functional copy of the cyclic nucleotide gated (CNG) ion channel B3 or A3 subunit genes to cone photoreceptors.

To date, the interim study reports that the experimental treatment is generally safe and well-tolerated, and describes “preliminary signs of biologic activity”.  Dosing two higher groups of adult patients and three groups of paediatric patients are included across both trials – 17 patients in B3 patients and 15 patients in A3.  At present, more than half of the patients already are enrolled with 3-6 month data available in second half of 2020.  Commenting on the milestone, Sue Washer, CEO of AGTC has stated that, “we are pleased that both of our achromatopsia clinical candidates are demonstrating preliminary signs of biologic activity for patients who have no current treatment options for a disease that significantly compromises their vision and quality of life. We are further encouraged by many patients’ real-world positive anecdotes. We are continuing dose escalation in order to determine the highest safe dose with the potential to provide maximal benefit.”