2023-08-23 14:46:51 ET
Summary
- 14-week data from the phase 2 LUNA study, using Ixo-vec for the treatment of patients with wet age-related macular degeneration, expected in late Q3 of 2023.
- Preliminary safety and efficacy data from phase 2 LUNA study, using Ixo-vec for the treatment of patients with wet age-related macular degeneration, expected Q4 of 2024.
- The age-related macular degeneration market is expected to reach $15.4 billion by 2032.
- Other gene therapies in the pipeline are being developed to target patients with retinitis pigmentosa and geographic atrophy.
Adverum Biotechnologies ( ADVM ) has made great progress lately in advancing the use of its gene therapy, known as ixoberogene soroparvovec [Ixo-vec], which is being developed for the treatment of patients with wet age-related macular degeneration [Wet-AMD]. It is currently in the process of running two clinical studies known as OPTIC and LUNA. The thing is that in the phase 1 OPTIC study, it was noted that patients given Ixo-vec were able to maintain best corrected visual acuity [BCVA] over a 2-year period. Not only that, but it was also shown that mean annualized injection were reduced by 81% to 98% in all patients. Why I believe it is important to highlight this biotech now is because there are two catalysts, which are expected to be released in the 2nd half of 2023. The first catalyst, which is expected in late Q3 of 2023, is going to be the release of aflibercept protein levels in patients who have undergone a minimum of 14 weeks of follow-up as of data cutoff. The second catalyst of which, is going to be preliminary results from the phase 2 LUNA study, whereby Ixo-vec was used to treat these patients with wet-AMD. With encouraging data to date over a 3-year period, plus the release of two catalysts approaching, I believe that investors might be able to benefit from any potential gains made here.
Ixo-vec For The Treatment Of Patients With Macular Degeneration
The main clinical program in the pipeline for Adverum Biotechnologies is Ixo-vec for the treatment of patient with wet age-related macular degeneration. Wet age-related macular degeneration is a result of abnormal blood vessels forming in the macula. It is a huge market opportunity for sure and any biotech that can greatly capture this space, can possibly generate a lot of revenue because of it. It is said that the age-related macular degeneration market is expected to reach $15.4 billion by 2032 . This is based on the overall macular degeneration market, which includes both wet and dry AMD. It is said that Wet AMD accounts for approximately of 10% of AMD cases . Even if only accounting for 10% of the expected market opportunity, it is still a good target market for Adverum to go after. The thing is that this biotech already ran a phase 1 study known as OPTIC . This study tracked Wet-AMD patients who received either the 6E11 or 2E11 dose levels. The end results were that patients gained a lot of benefit from just only having received one dose of Ixo-vec. It was noted that there was an 81% to 98% reduction in annualized anti-VEGF injections. In addition, 80% of patients given the 6E11 dose and then 53% given the 2E11 dose were supplemental free over a two-year period. Lastly, another huge positive highlight is that continuous therapeutic aflibercept protein levels were observed through 3 years in patients in the extension study. This last finding is also important, because it shows the mechanism of action of this gene therapy. That is, Ixo-vec is developed with an AAV.7m8 vector capsid carrying a cassette coding sequence of anti-VEGF protein aflibercept. The whole point of this protein is to allow for long-term delivery of anti-VEGF action over an extended time, with only one single intravitreal injection.
With this positive clinical data on hand, Adverum Biotechnologies was able to initiate the phase 2 LUNA trial . This is a double-masked, randomized study which recruited wet AMD patients who are 50 years of age or older. Not only that, but for patients to be recruited into this study they had to have been able to generate a response from anti-VEGF treatment. The first patient of this phase 2 study was dosed back in September 2022 . The primary endpoint of this study is going to be the average change in best corrected visual acuity [BCVA] from baseline to 1 year and the incidence and severity of adverse events [AEs]. The most recent milestone which was achieved for this program was that the company announced that enrollment of 72 wet-AMD patients was completed . Thus, this sets up the two key catalysts that I highlighted in the beginning for this phase 2 LUNA study. Hopefully, the results end up being highly positive. That's because data from the phase 1 OPTIC study, along with findings from the phase 2 LUNA study, will be able to inform the biotech of the design for a phase 3 study if warranted. Not only that, but Adverum will have to go up against other competitors, who have or are already dominating the wet-AMD space. The first of which is Regeneron Pharmaceuticals ( REGN ), because of its drug EYLEA, which has been approved to treat these patients. However, it has had sales of its drug slip to $1.5 billion in Q2 of 2023 because of substantial competitive pressure from rival Roche ( RHHBY ) with VABYSMO. However, it might be able to capture a lot of lost market share thanks to the FDA approving its higher dose version of EYLEA. Speaking of Roche, this is another possible competitor that Adverum Biotechnologies may ultimately have to deal with. A competitive advantage for it, should it get its gene therapy approved for wet-AMD, is that it will only need to be given once over a several year period. Whereas these other drugs will require frequent injections.
Financials
According to the 10-Q SEC Filing, Adverum Biotechnologies had cash, cash equivalents and short-term investments of $141.5 million as of June 30, 2023. This biotech is in good shape with respect to the cash on hand that it has. The reason why state that is because its cash burn rate is not that high and gives it plenty of quarters to fund its operations. In the most recent Q2 2023, its total expenses for the period ending June 30, 2023, were $33.1 million. With the cash on hand, it believes that it will be able to fund its operations into 2025. However, being that it has two data readouts expected in the 2nd half of 2023, the financial need might change. That's because if either it releases positive data from either of these catalysts, then the biotech may not hesitate to raise cash right away.
Risks To Business
There are several risks that investors should be aware of before investing in Adverum Biotechnologies. The first risk deals with the release of the 14-week follow-up results from the phase 2 LUNA study, which is using Ixo-vec for the treatment of patients with wet-AMD. These results are expected to be released in late Q3 of 2023. There is no guarantee that aflibercept protein levels were maintained as patients were monitored, even though this was observed from the conclusion of the phase 1 OPTIC study. A second risk would then be with respect to the preliminary safety/efficacy data expected for a cohort from the phase 2 LUNA study, which is expected to be released in Q4 of 2023. There is no assurance that the data will be positive, nor that the data will be viewed positively. A third risk to consider would be the competition in the wet-AMD space. Even if Ixo-vec gets through all clinical studies and is ultimately approved, it will have to go up against Regeneron Pharmaceuticals with EYLEA and Roche with VABYSMO. The fourth and final risk would be dilution. Despite the guidance that it will have enough cash into 2025, I wouldn't bet on a cash raise coming sooner, especially if the two data readouts in the 2nd half of 2023 are positive.
Conclusion
Adverum Biotechnologies had done well to advance its gene therapy candidate Ixo-vec thus far for the treatment of patients with wet-AMD. What investors can look forward to in the coming months would be the two data readouts, which are expected to take place in the 2nd half of 2023. If results from these studies turn out to be positive, then that would allow the company to possibly advance to a pivotal phase 3 program for the treatment of this patient population. Besides advancing Ixo-vec for the treatment of patients with wet-AMD, it is also developing gene therapies for other eye diseases like Geographic atrophy and retinitis pigmentosa.
For further details see:
Adverum: H2 2023 Data Readouts For Wet-AMD Gene Therapy