18 Oct Adverum Biotechnologies Presents Additional Clinical Data From its Phase I Intravitreal Gene Therapy for Wet AMD
Adverum Biotechnologies (NASDAQ: ADVM), a clinical-stage Company focused on developing therapeutics for ocular and rare diseases through gene therapy, released additional clinical data from its ongoing OPTIC phase 1 clinical trial of ADVM-022. ADVM-022, the Company’s lead ocular candidate, is an adeno- associated virus (AAV). 7m8-aflibercept, which uses a proprietary capsid (AAV.7m8) for the treatment of wet age-related macular degeneration.
The data was presented at the Retina Subspecialty Day Program of the American Academy of Ophthalmology (AAO) 2019 Annual Meeting in San Francisco, CA. OPTIC Phase I is a multi-center, open-label, dose escalation trial to test the safety and efficacy of ADVM-022 in patients with Wet AMD, who are amenable to anti-vascular endothelial growth factor (VEGF) treatment. The Data from the first cohort will be discussed with key opinion leaders at the conference.
The first cohort has six patients who were administered ADVM-022 at a dose of 6 x 10^11 vg/eye, while the second cohort has an additional six patients receiving a dose of 2 x 10^11 vg/eye, based on the anatomical response from the first cohort. The treatment involves the administration of a tapering prophylactic corticosteroid regimen. Adverum announced the plans to initiate a third and fourth cohort with 9 patients each with doses of 2 x 10^11 vg/eye and 6×10^11 vg/eye respectively. Additionally, patients in the third and fourth cohorts will receive prophylactic steroid eye drops instead of prophylactic oral steroids to treat inflammation.
In September 2019, the Company reported data from the first cohort of the OPTIC study, which demonstrated that a single ADVM-022 injection was adequate to maintain vision, proved by a stable mean BCVA compared to baseline, with zero rescue injections for any of the patients. The subjects also showed retinal anatomy improvements as observed on OTC Scans. The candidate was shown to have no serious adverse events, dose limiting toxicities or Grade 3 adverse events. Inflammation, which is characteristic of ocular gene therapies, was also shown to be manageable with steroids.
Aaron Osborne, MBBS, chief medical officer of Adverum commented
“The clinical profile of ADVM-022 demonstrates this gene therapy’s potential to be a significant advance for patients with wet AMD. It is very encouraging that there continues to be zero rescue injections in this cohort of treatment-experienced patients with more than 6 months follow-up on all patients. We are expanding the development of ADVM-022 and are excited to share that enrollment is now open for the third cohort in OPTIC. We look forward to being able to deliver this novel intravitreal gene therapy candidate as soon as possible to patients with wet AMD and diabetic retinopathy, our second indication for ADVM-022”.
Furthermore, Adverum plans to submit an investigational new drug application for the treatment of ADVM-022 in diabetic retinopathy in the first half of 2020 as per the Company’s future outlook.
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Addressing Unmet Needs in Macular Degeneration
Macular Degeneration is caused by the age related deterioration of the central portion of the retina named Macula. Macula is responsible for focusing the central vision in the eye and regulates reading, driving, facial and color recognition abilities. It collates the images from the center of the field of vision, and sends it to the optic nerves, so that it can be relayed to the brain. Macular degeneration is characterized by wavy or blurred vision and loss of central vision eventually, though peripheral vision may still be working fine.
The Disease is categorised into “Dry” or “Wet” with an estimated 85% of the cases being “Dry” or atrophic and over 15% of the cases being “WET”. It progresses in three stages namely early-AMD which is characterised by yellow deposits named Drusen being accumulated underneath the retina. The Intermediate stage sees some changes in vision and pigment in the retina followed by the final Late AMD stage, where vision loss is noticeable.
Though the exact cause of this illness is still unknown, certain hereditary and environmental factors have been found to play a crucial role. Age is one of the most important factors with people over 55 years at a greater risk of contracting the disease. In addition genetics, a family history of AMD and smoking are some of the other factors that can cause this disease.
The disease is the leading cause of vision loss for people over 60 years in the U.S, affecting an estimated 11 million people in the United States, and is likely to reach epidemic proportions by 2050, affecting over 22 million Americans, in the absence of research and treatment breakthroughs. According to an estimate, the direct cost of vision loss in North America is over $512.8 billion, and the indirect costs were $179 billion.
According to a report by Transparency Market Research, the global macular degeneration treatment market that was worth over US$ 6.1 billion in 2017 is likely to grow at a CAGR of 6.4% to reach US$ 11.1 billion by 2026. The increase in ageing population and rise in awareness levels will propel the growth in the market.
There is no cure for this illness as yet; however some research breakthroughs are providing, hope for the patients. Current treatment options start with nutritional therapy, especially focused on an antioxidant rich diet. Laser photocoagulation was the earliest treatment for leaking blood vessels in wet AMD; this was followed by Photodynamic Therapy (PDT) with Visudyne™, wherein a Visudyne™ is injected intravenously in the patients’ arm, which is then activated through shining non-thermal laser light into the eyes. This treatment was a considerable improvement over conventional therapeutic options as it used low-level, non-thermal laser to seal off leaking blood vessels, while leaving the healthy ones intact.
However, these cannot prevent reoccurrence of the illness leading to multiple treatment sessions. Most importantly they can only halt the degeneration or rate of progression of the disease and cannot restore lost vision. Additionally, only 10-15% of CNV lesions are eligible for laser treatment. They also have side-effects such as scarring or additional vision loss on account of the use of laser.
Hence there is a need for a major breakthrough that can prevent repeated reoccurrence of the condition after treatment and offer relief from all forms of wet AMD.
Adverum develops gene therapy products that are designed to create sustained expression of a protein. The Company has extensive knowledge and expertise in clinical development, novel vector discovery, scalable process development, assay development and practices rigid quality control measures, conforming to current Good Manufacturing Practices (cGMP).
The Company’s pipeline consists of ADVM-022 for the treatment of Diabetic Retinopathy, for which the Company plans to file for an NDA in 2020. Its Hereditary Angioedema (HAE) program is presently under preclinical development. Adverum has entered into collaboration with Regeneron Pharmaceuticals to develop AVA-311 for the treatment of Juvenile X-linked Retinoschisis (XLRS). The agreement also covers 3 undisclosed targets for ophthalmic diseases, and encompasses research, development and commercialization of the candidates.
Directed Evolution is the Company’s next-generation vector development technology that uses a library of engineered AAV capsid genes, to narrow-down and shortlist a select number of engineered AAVs with the desired characteristics.
The Company uses the Baculovirus Expression Vector System (BEVS) for the production of its AAV’s, offering an industrialized and highly scalable manufacturing method.
- Gene-based therapies, especially those focussed on AAV delivery vectors hold a lot of potential for growth in the future; the Company is building a robust pipeline of candidates to address a pressing need for unmet needs in the ocular therapeutics space.
- In April 2019, the FDA had put a hold on ADVM-022 for want of more information regarding the Company’s manufacturing process such as chemistry, manufacturing and controls information, which was later lifted in May 2019 to allow for the second cohort in the company’s OPTIC Phase 1 trial for wet age-related macular degeneration (wet AMD). The Company quickly resolved the concerns raised by the FDA and ensured that its trail continued without any setbacks.
- Adverum has entered into strategic partnerships with Regeneron and Editas, a very critical component for the growth of any clinical stage company. The Company will benefit from leveraging Regeneron’s considerable developmental and regulatory experience to advance its clinical candidates to a speedy commercialization.
- Clinical trials are fraught with risk and are unpredictable. The Company will do well to build a diverse pipeline of candidates to face any setback in its clinical trials, so that it does not negatively impact its future prospects.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
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