June 1, 2023
By Kristen Dalli, Managing Editor, Review of Myopia Management
At this year’s Global Specialty Lens Symposium, Mark Bullimore, MCOptom, PhD, and Ian Flitcroft, DPhil, presented on Vyluma’s CHAMP (Child Atropine for Myopia Progression) Study, which evaluates NVK002, a preservative-free, low-dose atropine in two concentrations — 0.01% and 0.02%. The CHAMP Study marks the first true placebo-controlled three-year study, and included both U.S. and European children. The primary goal of the study is to generate safety and efficacy data to support FDA approval of a new pharmacological treatment for myopia. Low-dose atropine is not FDA-approved to treat myopia.
CHAMP is the first study to evaluate a broad cross-section of children ranging in age from 3 to 17 years. It is the first study to include children across six countries and across a broad range of races and levels of myopia (from -0.50D to -6.00D).
Measuring Efficacy in Three Different Ways
In a clinical trial such as this, safety and efficacy are of particular interest. During his presentation, Dr. Flitcroft explained that there were three measures of efficacy for the CHAMP Study: biometric, refractive, and responder analysis, the last of which is a request from the FDA.
Dr. Flitcroft explained, “Biometric analysis asks the question: does the axial length slow down? Refractive analysis looks at the mean change from baseline in refractive error. Basically: does this treatment slow down myopia progression? The last one is an FDA request; it is how they analyze trials and relate a trial result to the individual patient, which is responder analysis. This is a metric of how many people meet a pre-specified endpoint. For our study, this endpoint is progression of less than -0.50D over three years. This is a really relevant clinical endpoint because what that means is that most of those kids’ glasses would not need to be changed or updated over that time.”
Drs. Bullimore and Flitcroft also made an excellent point as to why this metric is so important as it relates to practice management and getting parents on board to treat their children’s myopia. When practitioners have parents in their exam room, and their child’s glasses do not need to be changed at the follow-up visit because of this pharmaceutical intervention, the practitioner has succeeded at impressing that parent. Most parents come into the office with the expectation of spending a few hundred dollars on a new pair of glasses, and Drs. Bullimore and Flitcroft explained that the results from the CHAMP Study may support that this pharmaceutical agent could prevent some kids with myopia from needing stronger prescriptions as frequently.
0.01% vs. 0.02%
When looking at NVK002 in the 0.01% concentration, the drug met clinical significance in terms of biometric, refractive, and responder analysis. Compared to the placebo, NVK002 at 0.01% slowed axial length growth and had a lower change from baseline in refractive error in the three-year trial. The responder analysis showed that compared to a normal level of progression, 30% of children using NVK002 at 0.01% did not progress more than -0.50D at the end of 36 months. Importantly, 40% of the children using the drug did not progress more than -0.75D over that time. Such a small progression over three years should not be noticeable to the child. Dr. Flitcroft suggested this was potentially an indication that use of this investigational drug could positively impact those children’s visual outcomes. The trial also showed that NVK002 in the 0.02% concentration slowed axial length growth, but it did not reach statistical significance when it came to either refraction or responder analysis.
NVK002 Was Very Well Tolerated in Terms of Health and Safety Risks
Overall, Dr. Flitcroft shared that NVK002, in both concentrations, was very well tolerated for patients and did not raise any significant safety concerns. There were no serious ocular or systemic events related to the use of the drug, and very few children dropped out of the study due to medication related issues.
One of the critical factors to consider when looking at the health and safety of any drug is NNT, or “number needed to treat.” Dr. Flitcroft explained that this is a standard metric in assessing drugs, and it is the number of patients needed to treat with NVK002 to prevent one additional child from progressing -0.50D over three years. “With NNTs, the higher the number, the less effective the drug,” he said. “We found that the NNT for NVK002 is 9. ” This is comparable with many commonly used ophthalmological medications. The NNT for resolution of bacterial conjunctivitis within five days is also 9.1
Dr. Flitcroft also encouraged the audience to be aware that parents will not have to worry about their kids tolerating the drops, as the CHAMP Study showed very few issues in this area. “Kids really do take them without too much bother at all and for extended periods of time,” Dr. Flitcroft said. “The attractive part of these results is that young patients and low myopes tend to respond best of all. This is an ideal early intervention group. Some of these kids will be too young for a contact lens intervention, but you do not want to delay treating them. Or, you do not want to try to force them into a contact lens, and they have a poor experience with it from such a young age. So, this allows them to get into atropine early and move into lenses later.”
The ‘Wild West’ of Compounding Pharmacies
To wrap up the presentation, Dr. Bullimore discussed why FDA approval is important from the standpoint of moving away from compounding pharmacies. He explained that while the FDA has standards for sterility and the potency of approved drugs, the way compounding products are produced lead to different methods and standards for sterility. Additionally, the failure rate where FDA-approved drugs do not meet their specifications can be around 1-2%. Comparatively, studies of drugs that have come from compounding pharmacies may show much higher failure rates, even as high as one in three. From a practitioner’s perspective, this means that the formulation they intend to give to their patients may not actually be what the patient receives ultimately when it comes from a compounding pharmacy versus a drug that is pharmaceutically manufactured and approved by the FDA.
The researchers explained that should NVK002 receive FDA approval, it would resolve many of these issues for practitioners. They will not have to worry about inconsistent state regulations at compounding pharmacies, whether the final formulation will vary between different compounding pharmacies, if the product the patient receives has been stored correctly, or if any preservatives have been added to the drug. Without this worry, practitioners might feel less skeptical about prescribing an atropine solution to their myopia patients, and parents would also feel less apprehensive about giving their children these drops.
Dr. Bullimore shared a message of hope about the future of myopia management. “We need to move away from compounding pharmacies, where we often do not have any great assurances of what is in the bottle,” he said. “If we have something that’s FDA-approved, there will be greater assurance and greater uptake. This could offer a safe, effective, and easy way to initiate myopia treatment in even our youngest myopia patients.”
The presenters also left attendees with a critical piece of advice for practitioners: don’t wait for myopia to progress. The best course of action is to start myopia interventions as early as possible, as this is likely to yield the best outcomes.
“We often get asked, ‘Should I wait and demonstrate progression in a child before I initiate treatment?’” Dr. Bullimore said. “Personally, I say absolutely not. If you’ve got a myopic child with clear recent onset, a -1.00D 7-year-old let’s say, where they haven’t previously had myopia, there is a very high probability that that myopia is going to progress, and it’s never going to progress as fast as it does in the first year. So, it’s key to get in early.
“Pediatric myopia is a rapidly growing concern,” Dr. Bullimore continued. “While we know that some lifestyle factors contribute, we have to get on top of it because the long-term consequences are dramatic. There’s a clear benefit to slowing myopia. We’ve got to get in there early because myopia starts at a young age and stabilizes later.”
1 Sheikh A, Hurwitz B, van Schayck CP, McLean S, Nurmatov U. Antibiotics versus placebo for acute bacterial conjunctivitis. Cochrane Database Syst Rev 2012;(9): CD001211.)