Privately held SARcode Bioscience Inc. has enrolled the first patient in OPUS-1, its pivotal Phase III trial of topical SAR 1118 ophthalmic solution. OPUS-1 will study the safety and efficacy of SAR 1118 in the treatment of dry eye.
SAR 1118 is a first-in-class molecule that inhibits T-cell inflammation by blocking the binding of two key cellular surface proteins – lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) – that mediate the chronic inflammatory cascade. In addition to dry eye, the compound is under investigation for other ocular inflammatory conditions, including diabetic macular edema.
The OPUS-1 trial will randomize approximately 588 patients to SAR 1118 5.0 percent ophthalmic solution or placebo twice daily over 12 weeks, according to Charles Semba, SARcode's chief medical officer. Co-primary endpoints of the study are corneal fluorescein staining score and visual-related function score (reading, driving at night, computer use and television viewing) as measured by the Ocular Surface Disease Index. SARcode also will evaluate safety and tolerability of SAR 1118 compared to placebo at 12 weeks.
Powering up the numbers – 588 patients in the Phase III compared to 232 in Phase II – is the only significant difference between the two studies, according to Semba.
"The OPUS-1 study aims to replicate the positive results observed in the Phase II dry eye trial, which demonstrated increases in tear production as early as two weeks, an improvement in corneal staining and better visual-functional outcomes in the SAR 1118 treatment groups compared to placebo," he said.
"Many companies have tried, and numerous sponsors have failed" to develop a therapy in dry eye disease, Semba added. "With the fact that we have seen a positive biologic signal in Phase II, we didn't want to get too fancy and make too many alterations" in the Phase III trial design.
The Brisbane, Calif.-based company expects to complete the OPUS-1 study and report topline data in mid-2012.
SARcode was launched in 2006 after purchasing LFA-1 inhibitor technology from Sunesis Pharmaceuticals Inc., of South San Francisco, for $2.6 million. SARcode quickly attracted a $37 million Series A financing by venture capital firms Alta Partners and Clarus Ventures, then worked quietly for a few years to develop the LFA-1 antagonists. (See BioWorld Today, Dec. 29, 2010.)
Among its seven employees, SARcode counts key members of the management team that helped to launch Lucentis (ranibizumab) at San Francisco-based Genentech Inc., including Semba and CEO Quinton Oswald.
SARcode has advanced SAR 1118 rapidly during the past 18 months. In May 2010, the company reported topline results of the Phase II proof-of-concept study, demonstrating improvements in both signs and symptoms of dry eye at 12 weeks compared to placebo.
Reporting in May at the Association for Research in Vision and Ophthalmology meeting in Fort Lauderdale, Fla., SARcode said the Phase II study also showed a statistically significant (p < 0.05) increase in tear production for SAR 1118 in as early as two weeks.
The market opportunity for dry eye is estimated at $1 .3 billion in the U.S. and growing. The condition is thought to affect some 20 million people in the U.S., and the number of patients is expected to grow substantially in the next decade due to an aging population and increased incidence of Type II diabetes, both of which contribute to higher rates of dry eye.
Restasis (cyclosporin emulsion 0.05 percent), a drug that initially was developed for dry eye in dogs before being studied in humans, remains the only therapy approved in the U.S. for the indication.
However, clinical studies of Restasis indicated the onset of action is nearly twice as long – 24 weeks – as SAR 1118. Unlike SAR 1118, Restasis also accounts for up to a 17 percent rate of ocular burning at the same dosage.
"The Restasis approval studies were over a six-month period, and they were able to get efficacy claims for tear production at six months," Semba said. "In our 12-week Phase II study, we saw increased tear production as early as two weeks, and we saw a fairly consistent trend through the 12-week experience for the patient.
"Without actually having to do a head-to-head comparison, which was not our intent, if we can achieve statistical significance at two weeks and 12 weeks, that certainly would be an improvement over the current state of the state," he added.
In July, SARcode scored $44 million in a Series B round, adding two investors and bringing the firm's total fundraising to about $73 million. (See BioWorld Today, July 18, 2011.)
The round "gives us sufficient operating capital to get our program to a [new drug application] filing" for SAR 1118, Semba said. Although the company is still targeting 2014, Semba hinted that an NDA filing could come earlier, depending on the number of required confirmatory or safety studies. "We'll have more clarity on that depending on the outcome of this trial," he said. "We'll see how the data play out."
When he joined the company in 2007, Semba never expected SARcode to pursue a Phase III trial, he admitted. "But one development has led to another, and this thing just keeps growing," he said, giving SARcode the option of seeking partners or building an in-house marketing team for SAR 1118. In fact, the company has already developed marketing and development plans even though commercialization is several years away. "We're preparing for all contingencies," Semba said.
In the meantime, SARcode is actively pursuing additional activities, Semba said, though he declined to discuss specifics. The company is known to be examining a mode of action similar to that of SAR 1118 to treat dermatologic disorders such as atopic dermatitis. "We're opportunistic," Semba said. "We want to leverage our internal expertise, broaden our horizons and deepen the pipeline."