Adverum Biotechnologies Announces Clinical Progress Across Gene Therapy Pipeline
- Dosed First Patient in Cohort 3 in the ADVANCE Phase 1/2 Trial of ADVM-043
- Submitted Investigational New Drug (IND) Application for ADVM-022
- Plans to submit an IND Application to the
FDAfor ADVM-053 in 4Q18
“We are excited to be able to share positive progress in our three lead gene therapy programs today and to share our continued commitment to improving the quality of life for patients with unmet medical needs,” said
- The first patient in Cohort 3 was dosed with ADVM-043 gene therapy in the ADVANCE Phase 1/2 clinical trial
- Adverum expects to report preliminary data from patients in Cohorts 1 through 3 in the ADVANCE trial by the end of this year
Based on a review of the preliminary safety data from patients in Cohort 2, the independent data monitoring committee (DMC) recommended dose escalation to Cohort 3, and the first patient was dosed with a single administration of ADVM-043 at a dose of ~1.5E13 vg/kg (1.2E15 total vg) in late
The ADVANCE Phase 1/2 clinical trial is a multi-center, open-label, dose-escalation study of ADVM-043 in patients with A1AT deficiency. Cohort 1 patients (n=2) received an intravenous (IV) dose of ADVM-043 of ~1E12 vg/kg (8E13 total vg), Cohort 2 patients (n=2) received a dose of ~5E12 vg/kg (4E14 total vg), and Cohort 3 patients will receive a dose of ~1.5E13 vg/kg (1.2E15 total vg). Per protocol, patients being treated with standard-of-care weekly IV infusions of A1AT protein are required to “wash-out” for at least two months prior to receiving ADVM-043. The primary endpoint in the ADVANCE trial is safety and tolerability, and secondary endpoints include changes in plasma concentrations of both total and M-specific A1AT levels. Adverum plans to use the preliminary data from the ADVANCE study to inform next steps, including potential further dose escalation. Additional information about this clinical trial can be found at ClinicalTrials.gov under trial identifier number NCT02168686.
- Submitted IND application for ADVM-022 to initiate a Phase 1
ADVM-022 long-term preclinical data in nonhuman primate model of wAMD was recently presented at the
In addition, the long-term preclinical data in nonhuman primate model of wAMD showed ADVM-022 induced sustained intraocular expression of aflibercept for up to 16 months following a single intravitreal injection. Robust levels of aflibercept protein were detected up to 16 months in aqueous and vitreous humor and, more importantly, in retina and choroid tissues, where neovascularization occurs in wAMD.
ADVM-053 for HAE
- Plan to submit an IND application to the
FDAfor ADVM-053 in the fourth quarter of 2018
ADVM-043 (AAVrh.10-A1AT) is designed as a single-administration treatment to potentially induce long-term A1AT protein expression. In a preclinical proof-of-concept study, ADVM-043 demonstrated robust protein expression above therapeutic levels in mice following either intravenous (IV) or intrapleural (IP) administration. In another study in non-human primates, evidence of stable long-term expression of hA1AT transgene was observed out to one year following IP administration of ADVM-043.
About Alpha-1 Antitrypsin (A1AT) Deficiency
A1AT deficiency is an orphan disease affecting approximately 100,000 individuals in
The market for A1AT deficiency therapeutics was approximately
Adverum’s gene therapy candidate ADVM-022 utilizes a proprietary vector capsid (AAV.7m8) carrying an aflibercept coding sequence under the control of a proprietary expression cassette and is administered as a single intravitreal injection. Vascular endothelial growth factor (VEGF) activity is associated with wAMD progression and vision loss. Anti-VEGF standard-of-care therapies administered every 4-8 weeks have shown the potential to prevent disease progression and preserve or even improve patients’ vision. Treatment with ADVM-022 is designed to minimize the burden of frequent anti-VEGF injections, the current standard-of-care treatment for wAMD.
About Wet Age-Related Macular Degeneration (wAMD)
Approximately 1.2 million Americans suffer from wet age-related macular degeneration (wAMD).The current average age of AMD patients is 80 years old. The number of people with the disease is expected to double to 4.4 million by 2050 as the population ages.
Wet AMD (wAMD) is an advanced form of AMD where blood vessels begin to invade the cellular space between layers of cells in the retina. These new blood vessels are often leaky, which results in fluid and blood in the retina and causes vision loss. While wAMD represents approximately 10% of the number of cases of AMD overall, it is responsible for 90% of AMD-related severe vision loss. The disease is more common in Caucasians than in people of other ethnicities; age-related macular degeneration accounts for more than 54% of all vision loss in this population. Each year, approximately 150,000 to 200,000 Americans develop wAMD, with the number expected to grow due to the aging US population.
Currently, wAMD is treated with frequent injections of anti-VEGF protein into the eye. Compliance with this regimen can be difficult for patients and their caregivers, leading to compliance deficiencies and loss of vision from underdosing.
ADVM-053 (AAVrh.10-C1EI) is designed as a potential single-administration treatment to provide sustained release of the C1 esterase inhibitor (“C1EI”) protein to eliminate protein level variability and prevent breakthrough angioedema attacks. In preclinical studies, a single intravenous administration of ADVM-053 increased C1EI protein expression above therapeutic levels.
About Hereditary Angioedema (HAE)
HAE is an orphan disease affecting approximately 8,000 individuals in the U.S. This disease is caused by a genetic mutation that results in low levels of C1EI. Low C1EI levels can be associated with sudden swelling and edema of respiratory airways, gastrointestinal tract, and extremities.
The current standard-of-care prophylaxis treatment regimen generally requires IV infusions or subcutaneous injections of C1EI 2-3 times a week, at an estimated cost of
Adverum is a clinical-stage gene therapy company targeting unmet medical needs in serious rare and ocular diseases. Adverum has a robust pipeline that includes product candidates designed to treat rare diseases alpha-1 antitrypsin (A1AT) deficiency and hereditary angioedema (HAE) as well as wet age-related macular degeneration (wAMD). Leveraging a next-generation adeno-associated virus (AAV)-based directed evolution platform, Adverum generates product candidates designed to provide durable efficacy by inducing sustained expression of a therapeutic protein. Adverum has collaboration agreements with
Statements contained in this press release regarding matters events or results that may occur in the future are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements regarding Adverum’s expectations to report preliminary data from patients in Cohorts 1 through 3 by the end of this year, Adverum’s plans to use the preliminary data from the ADVANCE study to inform next steps, including potential further dose escalation, and Adverum’s plans to submit an IND Application for ADVM-053 for
Contact for Adverum:
Katherine BockVice President Investor Relations & Corporate Communications 650-656-9347 firstname.lastname@example.org
Source: Adverum Biotechnologies, Inc.