Adverum Biotechnologies Reports Positive Interim Data of ADVM-022 Intravitreal Gene Therapy for Wet AMD

Source: Adverum Biotechnologies

Adverum Biotechnologies announced new interim clinical data from Cohorts 1-3 of the OPTIC phase 1 dose-ranging clinical trial of ADVM-022 intravitreal (IVT) injection gene therapy in patients requiring frequent anti-VEGF injections for their wet age-related macular degeneration (AMD) and provided a business update.

For the first time, interim data are being presented from patients in Cohort 31, 2 and updated data are being presented from Cohorts 1 and 2 following treatment with a single IVT injection of ADVM-022. April 1, 2020 is the cutoff date for all data being presented. According to Adverum, new data as detailed in the table below further demonstrate the transformative potential of ADVM-022 to greatly reduce anti-VEGF injection burden in wet AMD:

  • ADVM-022 continues to show robust efficacy
  • Long-term durability beyond 1 year from a single IVT injection with zero rescue injections in Cohort 1
  • Further evidence of a dose response:
 6×1011 vg/eye: 6/6 patients rescue injection free
–  2×1011 vg/eye: 8/113patients rescue injection free
  • ADVM-022 continues to be well tolerated with a favorable safety profile in all 3 cohorts:
  ADVM-022 related ocular AEs mild (69%) to moderate (31%)
–  No ADVM-022 related SAEs or non-ocular adverse events 
– No evidence of vasculitis, retinitis, or choroiditis
–  Ocular inflammation, when observed, has been responsive to steroid eye drops
  • Early evidence from Cohort 3 suggests that a 6-week prophylactic regimen of steroid eye drops results in fewer adverse events and less inflammation, compared to a 13-day prophylactic regimen of oral steroids as used in Cohorts 1 and 2. In all 9 patients in Cohort 3:
 No cellular inflammation graded at a score above 1+ in any patient
–  No patients have required more than steroid eye drops
–  Only 8 ADVM-022-related AEs in 4 patients have been observed, all mild or moderate
  • Early anatomic and vision improvements observed in Cohort 3, with first 5 patients with 20 weeks follow-up showing:
–  Mean CRT4reduction (-137.8 mm)
–  Mean BCVA5 gain (+6.8 letters)

OPTIC Phase 1 Clinical Trial Data:

Results Following a Single ADVM-022 Dose:

Cohort 1

Cohort 2

Cohort 31




n= 9

Dose ADVM-022

Higher Dose
6 x 10^11 vg/eye

Lower Dose
2 x 10^11 vg/eye

Lower Dose
2 x 10^11 vg/eye

Follow-up (median)

60 weeks

36 weeks

20 weeks

Prophylactic steroid regimen

13-day oral

13-day oral

6-week eye drops2

Rescue Injections:


Number of patients requiring anti-VEGF rescue injections

0/6 patients

2/6 patients

1/5 for first 5 patients with 20 weeks follow-up

Total anti-VEGF rescue injections

0 injections

8 injections

2 injections



Follow-up BCVA5 and CRT4:

52-64 weeks
(median 60)

32-40 weeks
(median 36)

First 5 patients with 20 weeks follow-up


All Patients
100% (6/6) Rescue Free

All Patients

Rescue Free Patients
67% (4/6)

All Patients

Rescue Free Patients
80% (4/5)

BCVA mean change from baseline (letters)






CRT mean change from baseline (mm)






1 The first 5 patients had 20 weeks of follow-up as of April 1, 2020. The remaining 4 patients had 4-12 weeks of follow-up, insufficient for assessment of efficacy.
2 In Cohort 3, patients received 6-week prophylactic topical steroid regimen in place of the 13-day prophylactic oral steroid regimen used in Cohorts 1 and 2.
3 4/6 patients from Cohort 2 and 4/5 patients from Cohort 3 with 20 weeks follow up
4 Central retinal thickness (CRT)
5  Best corrected visual acuity (BCVA)

Arshad M. Khanani, MD, MA, director of clinical research, Sierra Eye Associates and principal investigator in the OPTIC trial said, “It’s impressive to see the long-term durability demonstrated at the higher dose of ADVM-022 in a patient population that previously required frequent injections to maintain their vision and are now beyond one year of follow-up with no rescue injections. Additionally, preliminary evidence in Cohort 3 shows vision and anatomical improvements and that the 6-week prophylactic steroid eye drop regimen is effective at minimizing early ocular inflammation. These are very positive data, and it is exciting to see that this intravitreal gene therapy has the potential to completely change the treatment paradigm for patients with wet AMD.”

Aaron Osborne, MBBS, chief medical officer of Adverum, added, “We are encouraged by the robust efficacy signal and evidence of a dose response in the OPTIC trial with interim data from 3 cohorts. Also, momentum in OPTIC is strong as we are currently enrolling patients in Cohort 4 at the higher dose of 6 x 10^11 vg/eye using the same steroid regimen as Cohort 3. We look forward to reporting additional data in the second half of this year from OPTIC. Beyond wet AMD, we are on track with our plans to advance ADVM-022 in diabetic retinopathy, our second indication, and we continue to expect to begin enrolling patients in our planned clinical trial in the second half of this year.”

Business Update

  • Adverum reports $297 million in cash, cash equivalents and short-term investments as of March 31, 2020, compared to $166 million as of December 31, 2019. In February 2020, Adverum raised approximately $140.8 million in net proceeds from an underwritten public offering. The Company expects this quarter-end cash position to fund operations into 2022.
  • Due to COVID-19, and the shelter-in-place mandated in the State of California, Adverum implemented a mandatory work-from-home policy for all non-essential activities.
–  To minimize the chance of community infection, the company has limited on-site activities to only the most time-critical or necessary operational activities.
–  Pursuant to the SEC’s recent order under section 36 of the Securities Exchange Act of 1934, Adverum now expects to file its Form 10-Q for the first quarter of 2020 with the SEC on May 28, 2020.

2020 MilestonesFirst half

  • Submit an investigational new drug application for ADVM-022 in diabetic retinopathy, a key VEGF-driven cause of vision loss among working-age adults

Second half

  • Present data from all four cohorts of the OPTIC trial
  • Begin enrolling patients in a planned Phase 1/2 clinical trial for ADVM-022 in diabetic retinopathy to expand Adverum’s clinical development pipeline


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