Somebody’s got to be the first, the pioneer, the risk taker.  Two publicly traded companies, Genvec (NASDAQ:GNVC) and its big pharma partner, Novartis (NYSE:NVS) have taken on this moniker.  Genvec is a pioneer in the design, testing and manufacture of viral vectors (adenoviral-based products) and Novartis is a big pharma company with the money ($248B market cap) and courage to move a gene therapy product into first-in-man clinical trials.  GenVec’s lead product candidate, CGF166, is licensed to Novartis and is currently in a Phase 1/2 clinical study for the treatment of hearing loss and balance disorders.

The Genvec / Novartis gene therapy approach

Approximately 90% of hearing loss is sensorineural, characterized by loss of sensory hair cells in the inner ear.  These sensory cells are critical to both hearing and balance and can become damaged or destroyed due to aging, infection, trauma from certain medications, or exposure to noise.  The goal of the therapy is to regrow the damaged sensory cells and restore hearing.

A common surgical procedure is used to gain access to the inner ear where the drug product (CGF 166) is directly infused. CGF 166 uses a viral vector to deliver the atonal gene (Atoh1) to the supporting cells of the inner ear.  The introduction of the Atoh1 gene triggers the conversion of supporting cells into sensory hair cells in the inner ear.

The Trial

The trail is a phase I/II study that will evaluate the safety / efficacy of the drug as well as the delivery mechanisms (vector, surgical procedure and infusion process).  Who is eligible to participate? Subjects must have bi-lateral, acquired, severe to profound hearing loss.  This counts out those persons with congenital (hereditary) hearing loss like my son.

The primary endpoint is to measure changes in hearing before treatment and after treatment.  Prior to treatment, patient baseline hearing thresholds are established (frequencies 0.125 KHz to 16 KHz).  After treatment, hearing threshold improvements greater than 10db can be considered clinically significant. The trial began recruiting in 2nd QRT of 2014 (at 3 sites: Kansas, MD and NYC) and the first patients were dosed in 4th QRT of 2014.

The Principal Investigator- Hinrich Staecker

 Dr. Staecker is the public clinical face of the trial.  He’s the Neil Armstrong of therapies to restore hearing.  Like Neil Armstrong, there are countless, nameless people who have dedicated their lives to the research that has moved the science to this point.  He will gain the notoriety if the therapy works and bear most of the criticism if the therapy doesn’t work or if somebody gets hurt. While many in the research community believe that therapies to restore hearing loss are 10 years away, Hinrich Staecker is the person who’s stuck his neck out and choose to move forward today.

Wrap up

 The hearing loss world is eagerly awaiting the data from the CGF 166 trail.  The questions are many:

  • Does the treatment improve hearing in humans (vs mouse)
  • How long does the treatment last (4mos, 12mos, lifetime)
  • Does the viral vector delivery mechanism have long term adverse effects on humans

There is no shortage of heroes in this effort.  Not only the ones mentioned above but consider the patients who volunteered to participate in the trial.  An excerpt from the Novartis website “Hearing loss can be frustrating, isolating, and disabling — suffering that is evident from the reaction Hinrich Staecker received after the trial’s launch. Following coverage of the clinical study in the magazine New Scientist in April 2014, he received more than 600 emails and dozens of daily phone calls from potential patients. “There’s a huge amount of interest in this,” he says.