When Sound Pharmaceuticals Inc. initially submitted an investigational drug application to the FDA for SPI-1005 in the prevention and treatment of hearing loss, it caused a moment of confusion for regulators.

While hearing loss is a well-addressed indication on the device side, with its hearing aids and cochlear implants, the FDA's Center for Drug Evaluation and Research had no division dedicated to otologic drugs, and no need of one until Sound prepared to enter the clinic with its first product for noise-induced hearing loss.

"It's been an educational process for us," said Jonathan Kil, president and CEO of Seattle-based Sound, which recently began Phase I testing of SPI-1005, a selenium-based small molecule designed to mimic glutathione peroxidase to treat, and potentially protect, auditory hair cells damaged by loud noises.

The study is evaluating SPI-1005, a twice-daily oral capsule, in 32 healthy volunteers, with the aim of determining safety at high doses of administration, as well as confirming the drug's absorption, distribution, metabolism and pharmacokinetic profile.

Later this year, Sound expects to start two Phase II trials, one with the U.S. Army and one with the U.S. Navy. Both studies will test the ability of SPI-1005 to prevent and treat hearing loss in military personnel exposed to intense noise as part of routine training, such as handheld rifle training, which can involve "firing hundreds of rounds over a two- to three-day time frame," Kil said. "While they have hearing protective devices in place, a significant percentage of them will develop not only temporary hearing loss but permanent hearing loss."

In fact, he added, "hearing loss is the leading cause of disability in the [Department of Veterans Affairs]."

Sound has ongoing collaborations with the Army and Navy, both of which agreed to fund Phase II and Phase III trials of SPI-1005, and would help facilitate product sales to the Department of Defense upon FDA approval.

Outside the military, SPI-1005 could become important in the prevention and treatment of noise-induced hearing loss. As the third leading chronic disorder - behind high blood pressure and arthritis - hearing loss affects twice as many people as diabetes and three times as many as vision loss.

"Our environment just gets louder and louder," Kil said. "Anytime you go to a bar or restaurant and have to raise your voice to be heard, you're already exceeding [Occupational Safety and Health Administration] limits."

Add to that the fact that some jobs lend themselves to loud noises - construction, manufacturing, mining, forestry and aviation are a few tracked by OSHA - and the increasing popularity of gadgets such as MP3 players that pipe "amplified noise directly into the ear," Kil said.

Once into Phase II, SPI-1005 will be evaluated for its ability to treat temporary hearing loss within a two-week window following intense noise exposure and to prevent patients from developing permanent hearing loss.

"After exposure to a very loud sound, you might experience temporary hearing loss, and if it doesn't resolve in a couple of days," it could lead to permanent loss, Kil said. With SPI-1005, Sound is hoping to attack that temporary loss early.

"The therapeutic window, we believe, is two days to two weeks," he added, and like drugs to prevent lasting damage from strokes, "the earlier we get to it, the better the outcome."

The drug's mechanism also might make it a potential treatment in retinal diseases, such as macular degeneration, and in neurodegenerative diseases, such as Alzheimer's and Parkinson's.

Sound anticipates taking SPI-1005 to the market on its own, especially since only a small sales force likely would be needed to sell it to the DoD. If the drug is to become available to the general population, the firm might consider partnership opportunities, Kil said.

SPI-1005 is the lead candidate to emerge from Sound's otoprotective program, and the company steadily is moving toward INDs in its two other programs.

The first of those is a drug candidate aimed at protecting the hearing of patients undergoing chemotherapy or antibiotic treatment. Last year, Sound reported results from preclinical testing showing that SPI-3005/6 prevented hearing loss in rats treated with cisplatin without interfering with cisplatin's antitumor activity.

Sound's other preclinical program focuses on regenerating auditory hair cells within the ear to restore hearing loss. That program is being funded by the Office of Naval Research and the Defense Advanced Research Products Agency (DARPA).

The regeneration platform is "our most ambitious," Kil said. "We've been able to do it in animals, and it works about a third of the time," though more research is needed before advancing that program.

Sound began operations in 2002 and has 10 employees. To date, the privately held firm has brought in about $3 million in seed money, though Kil said it's on the verge of closing a $10 million institutional round.

"I think this will be a very strong year for us," he said.

No Comments