Pharma Review

Recent years have seen a significant increase in basic scientific research as well as in clinical trial developments for tinnitus, hearing loss, and vertigo. Several of the otology pharma companies are in late-stage clinical trials and are traded entities on the public stock exchange. However, specifically for “inner ear disorders” it is important – when reviewing clinical trials – to keep in mind how hearing loss and tinnitus both differ in terms of the acute- versus chronic-stage.

Cochlear Info is not affiliated with any of the pharmaceuticals listed.

Ticker symbol: EARS

Programmes: acute tinnitus, acute hearing loss, vertigo, mental health supportive care

Auris Medical AG
Founded: 2003
CEO: Thomas Meyer
Website: www.aurismedical.com

Auris Medical is a leading Swiss-based pharma company within the field of inner ear disorders. Founded in 2003, Auris Medical has two advanced-stage clinical trials in its pipeline for the treatment of acute tinnitus (AM-101) and sudden hearing loss (AM-111), as well as a further preclinical-stage development for tinnitus (AM-102). In addition, a future drug candidate (AM-125) has been to be added to the pipeline for the treatment of vertigo (with phase-I trial results anticipated during Q3 2018). The same drug (betahistine) being explored in AM-125 has been found to have potential efficacy in the treatment of side-effects from antipsychotic medication (weight gain and drowsiness) and has been added to the pipeline under the name AM-201.

AM-101

AM-101 is currently the most late-stage clinical trial for the treatment of acute cochlear tinnitus (completed in 2018). After failing to demonstrate efficacy in the overall study population (in two separate trials – one of which was extended), Auris Medical is apparently attempting to bring AM-101 to market through partnering. The implication of that intention is therefore that there is still a belief the drug could work but that the inability to demonstrate efficacy in a placebo double-blinded trial is due to other factors such as patient profiles or clinical trial inconsistencies. The research behind AM-101 goes back many years when scientists at INSERM discovered intratympanic injections with an NMDA-receptor antagonist were observed to diminish the symptoms of tinnitus in rats. Based on a robust animal model, the AM-101 drug cleared both phase-I and phase-II trials in humans but did fail to demonstrate overall efficacy in the first of two phase-III trials (TACTT2) in 2016. The 2nd phase-III trial (TACTT3) was then extended to include additional enrollment of participants while adding the TFI as a 2nd co-primary efficacy endpoint. As an NMDA-receptor antagonist drug, esketamine (the active component in AM-101) works by blocking the effects of an excess release of glutamate which can lead to cell toxicity and subsequent nerve-fibre loss in the cochlea (a common observation seen after excessive noise exposure).

AM-111

AM-111 is a phase-III clinical trial programme for the treatment of sudden sensorineural hearing loss (administered while symptoms are still in the very acute stage). The application of the drug is via intratympanic injection. There are currently no approved therapies for SSHL. The first of two phase-III studies (“HEALOS”) failed to meet its primary endpoint; a subsequent on-going phase-III study (“ASSENT”) was halted before full enrollment had taken place. However, post-trial analysis showed that a subpopulation of trial participants – specifically those with profound hearing loss – did benefit from the intervention. A conference call hosted by Auris Medical on January 4th suggested that it is still their intention to try to bring AM-111 to the market (which would require a further clinical trial with a focus on the profound hearing loss subpopulation).

AM-102

AM-102 is a 2nd generation programme for the treatment of tinnitus. The preclinical development of AM-102 was first mentioned in the scientific literature back in 2009 as part of an industry review of emerging pharmacotherapies for the treatment of tinnitus. At the time, AM-102 was being developed by XIGEN SA as an intratympanic therapy but a new collaborator has since been found (King’s College London). Very little is known about AM-102 (incl. the undisclosed mechanism of action, delivery mode, and expected patient profile). However, as part of a conference call hosted by Auris Medical during March 2017, it was mentioned that the collaboration with KCL will continue for AM-102 with the aim to “identify and characterize our lead compound with high potential to treat acute tinnitus”. Although AM-102 is a 2nd generation programme, it would therefore seem that it is likely “just” an improvement upon AM-101 in the sense that it will target the same patient category (acute stage tinnitus) but with an enhanced treatment effect.

Noteworthy Media Releases

Website: www.aurismedical.com

Ticker symbol: OTIC

Programmes: tinnitus, hearing loss, vertigo

Otonomy Inc
Founded: 2008
CEO: David A. Weber
Website: www.otonomy.com

Otonomy is another leading pharma company with a focus on the treatment of ear disorders using an intratympanic delivery mode. Based in the United States, Otonomy has a number of drugs in its pipeline (both early and late stage, as well as market launched). Although the method of intervention is similar to Auris Medical, there is one point of differentiation: Otonomy has developed a sustained delivery exposure formulation for its platform thereby allowing drug application using a single intratympanic injection. The procedure is hence patient-friendly and may yield superior therapeutic results (due to the sustained exposure of the cochlea). Included in the Otonomy pipeline is OTIPRIO for the treatment of ear infections, OTIVIDEX for the treatment of vertigo-symptoms from Ménière’s disease, OTO-311 (renamed “OTO-313”) for the treatment of tinnitus, as well as preclinical trial programmes for hearing loss (OTO-413 for hidden hearing loss, OTO-5xx for ototoxicity-related hearing loss, and OTO-6xx targetting severe hearing loss).

OTIVIDEX

OTIVIDEX for the treatment of vertigo symptoms saw the first of the two phase-III studies (AVERTS-1) miss its primary endpoint causing the OTIC-share price to plummet. A 2nd phase-III study conducted in Europe demonstrated treatment efficacy with a placebo-response on par with earlier phase-II clinical data. Despite the initial setbacks, Otonomy is now pursuing a path to bring OTIVIDEX to the market.

Hearing Loss

At the beginning of 2018, a presentation was held at the JP Morgan Healthcare Conference with senior OTIC-management present. The update provided insights into what is slated to be three separate programmes for the treatment of three distinct types of hearing loss. Specifically, the most progressed component to the hearing loss programme, OTO-413, will target so-called “hidden hearing loss” while OTO-5xx and OTO-6xx will be indicated in cases of chemotherapy-ototoxicity and severe hearing loss, respectively.

Noteworthy Media Releases

Website: www.otonomy.com

Ticker symbol: ALSEN

Programmes: vertigo, hearing loss

Sensorion Pharma SA
Founded: 2009
CEO: Nawal Ouzren
Website: www.sensorion-pharma.com

French pharmaceutical, Sensorion Pharma, is currently in the process of advancing its early stage clinical trial platform for the treatment of inner ear disorders. But unlike Auris Medical and Otonomy, Sensorion Pharma has devised easy administration formulations of its drug pipeline thereby positioning itself differently with non-invasive interventions which do not require ENT expertise but where treatment could be handled by general practitioners (in a future market launch scenario). The platform includes SENS-111 for the treatment of symptoms of vertigo, SENS-401 for the treatment of sudden sensorineural hearing loss, and SENS-300 for the prevention of ototoxicity-induced hearing loss.

SENS-111

The patient profile for  SENS-111 includes people with acute symptoms of vertigo and works by reducing neuronal input from the vestibular nerve so as to create an alignment of vestibular signals from both the left and right ear. The drug (histamine) has no curative effects but aims to address the vertigo symptoms until they pass.

SENS-401

The clinical trial programme for SENS-401 is based on an enantiomer of SENS-218 (a drug only marketed in Asia named “azasetron”). SENS-401 has been shown to have superior efficacy (vs. SENS-218) with anti-lesional properties within the cochlea. The compound has demonstrated efficacy in terms of preventing noise-induced damage and is expected to head into phase-II clinical trials later on for sudden sensorineural hearing loss.

Website: www.sensorion-pharma.com

Ticker symbol: (privately owned)

Programmes: hearing disorders, psychiatry, neurology

Autifony Therapeutics Ltd
Founded: 2011
CEO: Charles Large
Website: www.autifony.com

Back in mid-2014, Autifony Therapeutics was slated to be the first mover for a future treatment for chronic tinnitus. Research had been under way for several years investigating a series of novel compounds that target the ion channels of the nerves of the auditory processing system. By modulating the specific ion channels in question, deficits such as tinnitus and certain types of hearing loss were thought to be treatable – something which had been confirmed in animal models. However, after successfully clearing a phase-I safety trial, the phase-II trial enrolling patients with tinnitus was halted already after a mid-term review in October 2015. The termination of the trial (named QUIET-1) was confirmed in April 2016. A 2nd trial investigating the same compound for the treatment of hearing clarity was also found to be lacking evidence of efficacy.

Website: www.autifonytherapeutics.com

Ticker symbol: (privately owned)

Programmes: hearing loss

Sound Pharmaceuticals Inc
Founded: 2001
CEO: Jonathan Kil
Website: www.soundpharma.com

As with Sensorion Pharma, Sound Pharmaceuticals has a clinical stage pipeline based on orally delivered medication. SPI-1005 and SPI-3005 are being investigated for the recovery of noise-induced and ototoxicity-induced hearing loss, as well as for the treatment of Ménière’s disease. The active component (ebselen) is believed to be capable of “flushing out” harmful chemicals that contribute to the degeneration of the inner ear while an injury of the cochlea is still in the acute stage. A preclinical stage programme (SPI-5557) is aimed at actual regeneration with the ambition of treating hearing loss.

Noteworthy Media Releases

● STOP Ototoxicity Study
● $30M Investment Round For Hearing Loss Programme

Website: www.soundpharma.com

Ticker symbol: (privately owned)

Programmes: eye disease (previously: epilepsy, tinnitus)

SciFluor Life Sciences Inc
Founded: 2011
CEO: Omar Amirana
Website: www.scifluor.com

Based on a derivative of Retigabine (marketed as “Trobalt” in Europe), SciFluor Life Sciences is investigating a more potent and selective Kv7 channel opener for the treatment of epilepsy and possibly for other conditions of a neurological origin (such as tinnitus). The drug candidate in question has been named SF0034 and the preclinical in vivo studies demonstrating efficacy for epilepsy and tinnitus were published back in 2015. Since then, very little new information has emerged as to a future clinical trial and intended patient profile. Company presentation material has previously suggested that a phase-I trial was expected to proceed in 2016 but this appears not to have initiated (as of yet). The 2016-annual financial statement released by the parent company of SciFluor Life Sciences (Allied Minds) indicates an IND and clinical trial progression can be expected in 2017 for SF0034. An earlier report from late 2015 by Kerrisdale Capital heavily criticised SciFluor Life Sciences (along with its parent company) and the science behind the drug development of SF034.

Website: www.scifluor.com

Ticker symbol: (privately owned)

Programmes: immunology, hematology, epilepsy, tinnitus

Knopp Biosciences Inc
Founded: 2005
CEO: Michael E. Bozik
Website: www.knoppbio.com

Another pharma company from the Pittsburgh area is Knopp Biosciences. The company was launched in 2005 and included in its pipeline is an ion-channel programme targeting the Kv7-channels. A status review of the usage of Kv7-channel openers for the treatment of epilepsy was provided in a presentation at the “Annual Meeting of The Japanese Pharmacological Society” in 2015 by Knopp Biosciences. However, progress in terms of bringing clinical trials underway has generally been slow, and in 2016, a representative from the company indicated that funding is lacking to support future clinical trials for the treatment of tinnitus, specifically (even though it is indicated via the website of Knopp Biosciences that tinnitus is an area of interest).

Website: www.knoppbio.com

Ticker symbol: (privately owned)

Programmes: hearing loss, other indications

Frequency Therapeutics Inc
Founded: 2015
CEO: David Lucchino
Website: www.frequencytx.com

Frequency Therapeutics is an early-stage pharma company developing therapies which rely on activating the body’s natural ability to heal through progenitor stem cells. The approach can have a number of uses within the field of degenerative disorders, but the recently established pharmaceutical is slated to investigate their proprietary PCA platform (Progenitor Cell Activation) for the treatment of chronic hearing loss first. An initial first-of-its-kind clinical trial (FX-322) was announced to be completed in late 2017 and registered with www.clinicaltrials.gov (use identifier: NCT03300687). The World Health Organisation estimates that as many as 1.1 billion young adults are at risk of developing hearing loss due to risky listening habits. There is hence a huge unmet need for inner ear therapies that tackle the problem.

Website: www.frequencytx.com

Ticker symbol: GNVC

Programmes: hearing loss, hemophilia, oncology, infectious diseases

GenVec Inc
Founded: 1992
CEO:
Website: www.genvec.com

Since 2014, GenVec has been conducting a phase-I/II trial (CGF-166) which examines the biological for safety and efficacy in relation to participants with severe/profound hearing loss. The trial is registered with www.clinicaltrials.gov (use identifer: NCT02132130). The first candidate to enroll in the trial (Rob Gerk) was featured in a number of media outlets. In early 2016, the trial was halted pending an interim review but has since resumed.

Website: www.genvec.com

Last date of revision: 28th January, 2018.