Ocular Therapeutix (NASDAQ:OCUL) is aiming to transform the treatment of eye diseases with sustained-release therapeutics, creating a paradigm shift from frequently administered topical ophthalmic drugs to an entire course of therapy in as little as a single dose.
“We have multiple late-stage product candidates based on our proven hydrogel technology platform, addressing the largest markets in ophthalmology, including glaucoma, inflammation and back-of-the-eye diseases like wet age-related macular degeneration (AMD),” chairman, president and CEO, Amar Sawhney, says in an interview with BioTuesdays.com.
Dr. Sawhney explains that current therapies for the front-of-the-eye are typically eye drops, which have a tendency to clear from the eye very rapidly. Patients have difficulty administering their medications properly or forget to take them altogether, creating compliance issues. Intravitreal injections for diseases of the back-of-the-eye are typically administered once or twice a month, which places an undue burden on both patients and caregivers.
“What we are trying to do is alter the delivery of drugs from several administrations a day, to a comfortable, non-invasive depot which can deliver a therapeutic regimen for up to 3 months in a single dose,” he adds. “For treatment of back-of-the-eye diseases, fewer injections will not only improve convenience for a patient but may limit side effects associated with frequent injections.”
The company also received FDA approval last year for its ReSure Sealant, a first-in-kind ophthalmic sealant for corneal incisions following cataract surgery. There were approximately 3.65 million cataract procedures in the U.S. last year.
“Our commercial focus for the ReSure Sealant is currently very limited but we intend to construct our own sales channel after approval of our first sustained- release drug for pain and inflammation, since both products address the same surgical market,” Dr. Sawhney says.
Ocular’s lead program for the front-of-the-eye is a one-month punctum plug, OTX-DP, delivering dexamethasone for the treatment of post-surgical pain and inflammation.
The company has completed enrollment in two Phase 3 clinical trials of OTX-DP and recently reported promising top-line data from the Phase 3a study and expects to announce results from the Phase 3b trial by the end of the current quarter.
Last November, Ocular announced positive results from a Phase 2 clinical trial for OTX-DP for the treatment of allergic conjunctivitis and plans to move into a Phase 3 trial in the first half this year. It also has initiated a Phase 2 trial for OTX-DP for the treatment of inflammatory dry eye disease.
Dr. Sawhney explains that steroids, such as dexamethasone, are known to increase intraocular pressure when used over long periods of time, but the company uses less than 7% of the eye drop equivalent dose. “This allows us to mitigate side effects associated with steroids and increase the number of diseases that can be addressed with the use of steroids,” he adds.
In addition, Ocular has initiated patient enrollment in a Phase 2b clinical trial with OTX-TP, delivering travoprost in an up-to-three-month punctum plug for the chronic treatment of glaucoma and ocular hypertension. The company hopes to report results of the trial in the second half this year.
According to Dr. Sawhney, limitations of current therapies for glaucoma, a leading cause of blindness, include poor compliance, as more than 50% of patients discontinue therapy within 12 months, resulting in diminished efficacy and disease progression.
In addition, current therapies for glaucoma are difficult to administer, need high concentrations, since less than 5% of the dose actually penetrates the intraocular tissue because of washout, and can cause side effects because of antimicrobial preservatives, he adds.
On the other hand, Dr. Sawhney says punctum plugs have the potential for sustained and tailored delivery over time, improved compliance, vastly reduced dosing frequency and reduced patient burden.
In its back-of-the-eye program, Ocular has signed an early-stage feasibility agreement with a fourth biopharmaceutical company to evaluate an oncology drug for the treatment of wet AMD. Feasibility studies with pharma partners for the sustained delivery of anti-VEGF drugs are expected to be completed in the first half this year.
Citing industry and research reports, Dr. Sawhney says Ocular’s hydrogel technology platform is targeting markets that currently total more than $9-billion in the U.S., including all inflammatory conditions at $2.9-billion, glaucoma at $2.1-billion, anti-VEGF at $3.3-billion and anti-infectives at $700-million.
In an earlier Phase 2 study with OTX-DP for pain and inflammation in 60 patients after cataract surgery, the company did not find any intraocular pressure spikes using a 7% of the eye drop equivalent dose. It also found effective absence of pain at day 8 and effective clearing of inflammatory cells in the anterior chamber of the study eye at day 14.
In allergic conjunctivitis, Ocular met with the FDA in December to discuss its Phase 2 data and next steps in the clinical development of OTX-DP. The FDA agreed to a refined Phase 3 protocol based on the Phase 2 trial results in two pivotal studies, with 72 patients each. In addition, the company will be allowed to submit safety data from its pain and inflammation studies to support a filing for regulatory approval.
Dr. Sawhney says a Phase 3 studies in allergic conjunctivitis are planned to start in the middle of the year, with data readouts expected by the end of the year.
That’s also the approximate time frame for data from a Phase 2 “exploratory” trial in 40 patients with dry eye disease caused by chronic inflammation. “A longer-term strategy will be formed by this study,” he adds.
Also by the end of the year, Ocular could have data from a Phase 2b clinical trial with 80 glaucoma patients, comparing OTX-TP against Timolol eye drops. The study is more than 50% enrolled.
Assuming efficacy of OTX-TP is achieved in the Phase 2b study, Dr. Sawhney says the company would move into two Phase 3 studies in the first half of 2016. The FDA has indicated that the studies will need to include 500 patients, of which 300 treated patients will be studied for up to six months and 100 treated patients for up to 12 months for safety evaluations.
Last August, Ocular raised approximately $66.5 million in net proceeds from an IPO to advance pipeline programs to late-stage development and commercialization.
Dr. Sawhney points out that the company runs its own clinical trials, with its own clinical research associates, runs its own databases and also does its own manufacturing. “As a result, our burn rate is significantly lower than other companies in the field. That, combined with our technology, differentiates us from the competition.”