By Caroline Copley and Ben Hirschler
ZURICH/LONDON (Reuters) - When Swiss biotech firm Auris Medical wanted to recruit patients to test its experimental hearing loss drug, it decided to enlist partygoers deafened by firecrackers on New Year's Eve.
In the weeks leading up to December 31, 2005 it advertised in the subway and on radio stations in Munich and Berlin, urging victims of sudden firecracker-induced hearing loss to turn up at designated clinics for treatment on January 1.
"We had just one single day of enrolment, we didn't know how many people would show up," Thomas Meyer, managing director of Auris, told Reuters.
Luckily, his gamble paid off and the small private company is now one of the leaders in what has been an empty space for the pharmaceutical industry.
Auris managed to recruit enough people to show that its compound AM-111 posed no safety risk and has since successfully completed a mid-stage trial in acute sensorineural hearing loss, or sudden deafness, involving 210 patients.
While there is no guarantee that its drug, which is injected through the eardrum, will pass muster in final-stage tests, the progress by Auris and a clutch of rival biotech firms is making large pharmaceutical companies sit up and take notice.
There are currently no approved disease-modifying drugs for hearing loss, which affects nearly a third of people aged 65 to 74 and half of those over 75.
But the science is developing and investor interest is growing, piqued by the huge commercial success of recent new treatments for sight loss, such as Lucentis from Novartis and Roche and Eylea from Regeneron and Bayer.
British charity Action on Hearing Loss conservatively puts the potential Western market for new drugs at $4.6 billion a year - a figure that could grow quickly as ageing populations swell the ranks of those with hearing problems.
"It's one of the few areas that, as yet, hasn't really been tackled by the drugs industry," said Kate Bingham, managing partner at SV Life Sciences Advisers, a venture capital firm with investments in new drugs for both eyes and ears.
Bingham sits on the board of Autifony Therapeutics - a hearing loss firm spun out of GlaxoSmithKline in which the British drugmaker retains a stake.
Historically, hearing loss has received little attention from Big Pharma, given the lack of obvious targets for drug intervention, the difficulties of running clinical trials and a widespread belief that most deafness could not be reversed.
Now the big companies are getting involved, although the work is early-stage.
"A drug that is therapeutic and priced right could be quite a blockbuster. That's why they've put their toe in the water," said Jonathan Kil, chief medical officer at Seattle-based Sound Pharmaceuticals, which is enrolling young iPod users in a trial of an oral drug for noise-induced hearing loss.
U.S. giant Pfizer is arguably the most advanced of the big players, with a drug in initial Phase I clinical testing trial for age-related sensorineural hearing loss that looks to enhance the function of existing hair cells.
Some of its biggest rivals are laying bets, too. Last year French drugmaker Sanofi inked a two-year research deal with privately held Dutch biotech firm Audion Therapeutics to develop small molecule drugs to improve hearing.
In October, Roche joined forces with venture capital firm Versant Ventures and biotech Inception Sciences to find molecules targeting ear hair cell protection and regeneration in the cochlea, the spiral-shaped cavity in the inner ear.
Cross-town competitor Novartis, meanwhile, struck a 2010 deal potentially worth more than $213 million with U.S. biotech GenVec to develop gene-based treatments to replace hair cells in the ear that transmit sound.
"We're looking at restoration as our main line of work and we're interested in whether there are chemicals that might also play this role instead of having to introduce a gene," said Novartis research head Mark Fishman.
"This is an area that's a bit more futuristic and ultimately restoring the hair cells will be the cure."
EYES AND EARS
Unlike new eye drugs, which work by inhibiting an unwanted process, hearing drugs will need to restore damaged function - a more difficult proposition.
Experts say the first drugs will target niche areas, such as damage caused by loud noise or as a result of chemotherapy.
"Hearing loss is not just one condition. It's like cancer - there are lots of different types and there is work to be done to segment the market," said Ralph Holme, head of biomedical research at Action on Hearing Loss.
Heading the field for noise-induced hearing loss is South Illinois University, which has launched a late-stage trial with the U.S. military for an drug to increase protection for people exposed to very noisy environments like soldiers.
Canada's Adherex also has a late-stage trial to test a drug that may protect against hearing loss caused by platinum-based anti-cancer agents in children.
While protective treatments could become available within the next few years, regenerative approaches - such as injecting stem cells into the ear or chemically intervening to switch on genes that control cell growth - are much further off.
Despite recent promising tests in gerbils, the potential to replicate this in humans is still uncertain, said Pascal Senn, an ear specialist at the University of Berne.
"If something grows inside the ear, you must be sure that it doesn't grow excessively or form tumors. There are a lot of roadblocks that need to be overcome in this field. It's highly risky, but I think it's also the hottest area," he said.
One intriguing possibility for the future is the convergence of future drugs and devices. Hearing aid manufacturers have certainly not been deaf to the noises from the pharma sector.
Sonova, the world's largest maker of hearing aids, has invested in two start-up companies - one in the United States for drugs to protect hearing and another Swiss biotech working on a treatment for acute tinnitus.
It bought U.S. cochlear implant manufacturer Advanced Bionics in 2009 in a bid to increase its focus on the inner ear and understand how drug treatments could work with implants.
"It will be interesting whether the innovation will be driven by pharma companies moving in or whether the hearing aid companies will branch out," said Auris' Meyer.
(Editing by Philippa Fletcher)