Video transcript is below:
Hello, my name is Michael Singer, MD, and recently at the Retina World Congress I presented some new data on subcutaneous migaldendranib (Ashvattha Therapeutics), the 24-week phase 2 study results for chronic dosing for the treatment of wet AMD and DME. Obviously, we know there's a big treatment burden for in-office intravitreal injections. This is a paradigm shift. This medicine is a subcutaneous injection that will treat both eyes with a single shot, and presumably we do it at home. It's a tyrosine kinase inhibitor (TKI) like other TKIs, that blocks other forms of vascular endothelial growth factor (VEGF). What's interesting is that it's cleared in the kidney, so there's no systemic or liver toxicity. It's uptake is only by the retinal pigment epithelial (RPE) cells and macrophages in actively inflammatory lesions. It's retained in the cells for 30 days and then cleared from the body in 2 days.
There was another medicine called X-82 (vorolanib; Tyrogenex), which was an oral medicine that had to be given every day. The trial was stopped because of many moderate liver and GI effects. Migaldendranib has few effects in general and no liver or kidney effects. It’s subcutaneous.
We are presenting the phase 2 data looking at 2 mg medicine being given either monthly or every other month subcutaneously. Patients were previously treated with either 3 intravitreal injections for AMD or 5 intravitreal injections for DME. They had to have a response, and then when we gave the last shot, they had to be able to dry up at month 1 but swell up at month 2 or 3. Patients were then given either monthly or every other month migaldendranib for each of the 2 diseases. In terms of supplemental injection criteria, if the central subfield thickness (CST) went above baseline, which was the day 1 number, patients could be supplemented. If they lost 10 letters, if they had increased hemorrhage, or if they had problems in the nonstudy eye, they potentially could get rescue injections.
Forty-three percent of wet AMD patients had bilateral disease, and about 78% of DME patients had bilateral disease. There was more swelling in DME than AMD, and the fellow eye had previously 6 injections in AMD and DME. So again, both eyes were frequent flyers.
It's important to understand, is the medicine safe? It turns out there are no liver or renal effects. In our study, there were 2 SAEs, which were cellulitis before dosing and a vitreous hemorrhage. The biggest reaction was injection site reaction of 8.6%. It was localized, transient, and mostly mild. Looking at the effect, migaldendranib dried up the retina in wet AMD: CST decreased by about 45 µm and BCVA increased by about 3 letters. In DME, CST decreased by about 69 µm and BCVA increased 4.5 by letters. Looking at the fellow eye, CST decreased in wet AMD by 30 µm and BCVA increased by 2.3 letters. CST did not decrease much in DME, but these were patients who didn't have a lot of swelling to begin with, although BCVA did increase by 2.3 letters.
Looking at it another way, this decreased treatment burden for AMD and DME in the study eye by an average of 80% and in the fellow eye by an average of 74.45%. In terms of supplemental criteria, basically 1 patient was rescued for a 10-letter loss, 2 were rescued for hemorrhage, and then the other rescues were due to increased CST above the treatment baseline. Seven of the patients who received supplemental therapy didn't even make it to baseline. They had some swelling that did not reach baseline, but they were rescued anyway, and 50% of the rescues actually occurred when the CST increased under 75 µm. So this is less than what is typically used as rescue criteria in other TKI trials.
In summary, migaldendranib is safe and well tolerated. It maintains BCVA and CST in both DME and AMD. What's really nice is you're going to decrease the need for supplemental injections because one shot treats both eyes, and obviously it's a novel first-in-class potential at-home treatment to supplement our patients who are receiving intravitreal injections for DME and AMD. We're going to present more study results later in the year. Thanks for watching. RP
