For this month's Retina Minute, I have the pleasure of speaking with my dear friend, Rahul Khurana, MD, who is a partner and president/CEO at Northern California Retina Vitreous Associates and a clinical associate professor in ophthalmology at UCSF Medical Center.
Dr. Khurana, you presented some interesting data on a new molecule from Genentech Roche for the treatment of patients with macular edema secondary to uveitis. Can you explain it to our readers?
Unfortunately, uveitic macular edema is the leading cause of vision loss in patients with uveitis. Even when you have systemic immunosuppression and good control of the uveitis itself, nearly 50% of patients with uveitis can still have persistent uveitic macular edema. We have some effective treatments for uveitic macular edema involving steroids. However, side effects involving increased pressure and cataract are usually rate-limiting steps, especially when patients need repeat injections, so there is an unmet need for alternative treatment options for these patients.
Interleukin-6 (IL-6) is an exciting new molecule. It is elevated in patients with uveitis, specifically in aqueous humor. There is a lot of strong scientific rationale to target this molecule. We know that when IL-6 is dysregulated, it causes corneal permeability, macular edema, and inflammation. What I presented at Academy Subspecialty Day was data on a new molecule called vamikibart, which targets IL-6. Phase 1 showed that suppression of IL-6 with vamikibart lasts up to 6 months in aqueous humor taps.
Tell us about the trials.
There were 2 phase 3 global clinical trials: MEERKAT and SANDCAT. These trials randomized patients with uveitic macular edema in 1:1:1 arms of a 0.25 mg or 1 mg vamikibart intravitreal injection compared with sham. They received 4 injections, and the primary endpoint was change in visual acuity after the injections. We found that patients improved about 10 letters with both doses of vamikibart compared with about 3 to 4 letters with sham. Vamikibart also decreased the retinal anatomy by about 200 µm in both doses.
We also saw a good safety signal. Despite their uveitis, patients had low rates of intraocular inflammation, cataract, and intraocular pressure and no cases of vascular occlusive vasculitis, which are the side effects we worry about with steroids. Vamikibart was tolerated through week 16.
How many patients were in the trials?
MEERKAT and SANDCAT had approximately 480 patients who were randomized.
Did higher doses do better?
The dosing was interesting. In MEERKAT, there was a dose effect. The 1 mg dose had a better response at vision, but there was not a dose effect in the SANDCAT study. The pharmacokinetic data showed that both the 0.25 mg and the 1 mg suppressed IL-6 up to 6 months.
Did both studies reach statistical significance?
Both doses met statistical significance for the primary endpoint in MEERKAT. In SANDCAT, the 0.25 mg did, but the 1 mg missed it with a P value of 0.057.
What is the next step?
We want to see the full-year data through week 52. It will be up to the regulators to look at the data, but I think it looks promising from what we have seen so far.
If this IL-6 molecule gets approved, how do you see it playing out in your treatment of this disease process?
It is good to have extra tools in the toolbox. We know that a lot of these patients, especially the really challenging ones, need repeat injections, so I think this is going to be a great option for patients who have pressure issues or complications. One of the effective attributes regarding steroids, is that the injection burden is much less. But I think vamikibart’s pharmacokinetic data so far shows that, even after the initial treatments, the suppression can last up to 6 months, so that is optimistic that there is durability. I think when we get the data from week 16 to week 52, we will have a better idea of whether these patients need an injection every month or not.
This is a fascinating molecule. We have been treating uveitis with 1 type of drug in different ways, but obviously the safety profile keeps us up at night. Having something else in our toolbox would make this treatment much easier to tolerate for patients who are being significantly affected by this condition.
I think the exciting part is that it is a new mechanism of action. We know steroids work, and now we are getting a little bit more specific looking at IL-6, which could be an exciting target for macular edema in general.
I agree. Thanks for being here, Dr. Khurana.
