Industry Insider is a timely chat with an ophthalmic industry thought leader.

Kim Brazzell, PhD

In his role as chief medical officer for Kala Pharmaceuticals, Kim Brazzell, PhD, has helped design the company’s proprietary mucus-penetrating particle technology, Ampplify, and develop new products based on the technology. Kala’s first FDA-approved product, Inveltys (KPI-121 1.0%), received approval in August. It uses the Ampplify technology to improve the treatment of inflammation and pain following ocular surgery and is the first FDA-approved, twice-daily corticosteroid to treat such symptoms. Inveltys will be released in January.

Ophthalmology Management: What do you see as the advantages of Ampplify?

Kim Brazzell, PhD: The mucus barrier is an innate defense mechanism throughout the body, protecting it from pathogens and allergens. Unfortunately, it can also trap drugs and hamper their ability to penetrate to the target tissue needing treatment. Ampplify is comprised of selectively-sized drug nanoparticles (200-400 nm) covered with a proprietary surface coating, allowing them to penetrate through the mucus more easily. For ophthalmology, this allows topically administered drugs to avoid being trapped and eliminated by the tear film mucins on their way to tissues such as the cornea and anterior chamber. Eventually, Ampplify may even have the ability to treat diseases at the back of the eye.

OM: As a twice-daily corticosteroid, what is the significance of Inveltys to patients and eye-care professionals?

KB: With Inveltys (KPI-121 1.0%), we think we’ve achieved what others in the ocular steroid space have attempted for years — a product with strong efficacy when dosed only twice a day with one of the best safety profiles in its class, particularly regarding IOP elevation.

In the Inveltys clinical program, statistical significance favoring Inveltys given twice a day was seen for both primary endpoints — complete resolution of intraocular inflammation and complete resolution of pain, both at Day 8 — in both Phase 3 trials. In pooled data from the two Phase 3 trials, significantly more Inveltys-treated patients resolved inflammation at Days 8 and 15 (p≤0.0001) and resolved pain at Days 4, 8 and 15 (p<0.0001). Safety and tolerability were excellent, with the most common adverse events, eye pain and posterior capsule opacification occurring in only 1% of Inveltys treated patients. IOP elevation was similar between Inveltys and vehicle.

OM: What new information can you share about your product pipeline?

KB: One of our primary products in development is KPI-121 0.25%, designed for the temporary relief of DED signs and symptoms. If approved, KPI-121 0.25% will be the first FDA-approved product for short-term treatment of DED.

We have completed one Phase 2 trial with KPI-121 0.25% and two Phase 3 trials, STRIDE 1 and STRIDE 2. In all three trials, we achieved statistical significance for the primary sign endpoint of conjunctival hyperemia. Regarding symptoms, we saw a significant improvement in ocular discomfort at Day 15 in our Phase 2 trial, with a p-value of 0.0489 in a post hoc analysis.

In STRIDE 1 we achieved statistical significance for both primary symptom endpoints — ocular discomfort at day 15 in all patients and ocular discomfort at day 15 in patients with more severe baseline discomfort. There were also good trends for treatment benefit for ocular discomfort in STRIDE 2, but that did not quite achieve statistical significance.

With these data, we believe we have compelling evidence for the safety and efficacy of KPI-121 0.25%, and we recently submitted an NDA. We also started another Phase 3 trial, STRIDE 3, and anticipate top-line results in late 2019.

We expect KPI-121 0.25% will be an excellent treatment option for episodic dry eye, which we believe represents 80-90% of all dry eye patients. These are patients that don’t experience constant symptoms but have periodic dry eye symptom “flares” that can wax and wane in response to environmental triggers such as dry or windy weather, allergy season or prolonged computer use. We are optimistic we can have this treatment on the market in the next year or two.

OM: How has the ophthalmic industry changed during your time in it?

KB: Well, with age comes wisdom, though I’d certainly trade some for youth (laughs). When I started 25 years ago, the “big pharma” companies, aside from Merck, had little interest in ophthalmic pharmaceuticals. While that’s definitely changed, the biggest difference is that there are a lot more small biotech companies now.

Back then, if you approached a funding group with an idea for an ophthalmic start-up, you’d probably get a pat on the back and be shown the door. Now, you’re seeing a lot of innovative, novel therapies from small companies, like Kala.

And, of course, there have been remarkable advancements in treatments. Treating conditions like AMD and diabetic eye diseases is now a reality, when before it was just a dream.

OM: Tell us about your role as Kala’s chief medical officer.

KB: At Kala, I am responsible for clinical, regulatory, medical affairs and project management. As such, I have overall responsibility for design and conduct of clinical trials, interactions with regulatory authorities and regulatory submissions, overall management of the various R&D programs and medical affairs activities, such as medical information and communication, education, post-launch clinical trials and field medical activities. My colleagues who help lead these activities are excellent and help make my job a lot easier. OM