Welcome to your weekly digest of approaching regulatory and clinical readouts. In the fourth quarter results are due from the second phase III schizophrenia trial of Intra-cellular’s (NASDAQ:ITCI) ITI-007, which in its first study proved effective and, most importantly, free from the side effects associated with older antipsychotics. A repeat would reaffirm its blockbuster potential.
Meanwhile, topline results from the phase III TACTT2 trial of Auris Medical’s (NASDAQ:EARS) tinnitus candidate AM-101 are expected in August. A European trial is also due to report before the end of the year. These could put it on track to become the first drug approved for the acute form of the disease, though earlier clinical data were mixed.
Pipeline in a drug
Intra-cellular's second phase III study is in 696 schizophrenia patients experiencing an acute exacerbation of psychosis, and subjects will receive 60mg or 20mg ITI-007, the active control risperidone (4mg), or placebo. The oral treatment will be given once a day in the morning for six weeks.
The primary endpoint is change from baseline at day 42 on the positive and negative symptom scale (PANSS) total score, and the key secondary endpoint is change in clinical global impression scale for severity of illness (CGI-S). When the first phase III trial reported positive results last September the company’s shares rocketed 87%.
In that trial 40mg and 60mg were given over four weeks versus placebo; the higher dose showed a statistically significantly greater improvement in the PANSS score. The improvement was seen after one week of treatment (Intra-Cellular’s schizophrenia success could tempt a buyer, September 17, 2015).
The project had no major side-effects and seemed free from the metabolic issues seen with some older drugs – it did not lead to weight gain or changes in metabolic measures.
ITI-007 is Intra-cellular’s lead asset, and is also in trials for bipolar disorder and agitation in dementia, with preclinical work in other mood disorders. According to EvaluatePharma’s consensus 2022 worldwide sales are forecast to reach $2.5bn, $1bn of which are through partnering the drug in Europe. It has an NPV of $3.4bn, nearly double Intra-cellular’s market cap.
It is wholly owned by the company, but partnering is essential to generating peak sales, and positive results could attract a buyer. ITI-007 is likely to be a first-line treatment, but availability of generic antipsychotics could affect its use in clinical practice.
ITI-007 will need to play on its impressive side-effect profile to claw out a place in the market. The top branded players are injectables, often with monthly dosing; preclinical work on a long-acting injectable version of ITI-007 has started.
All ears for tinnitus data
The co-primary endpoints in Auris's phase III TACTT2 trial are change in tinnitus loudness and the tinnitus functional index score, which measures tinnitus impact and burden, from baseline to day 84.
AM-101, also known as Keyzilen, is an NMDA receptor antagonist designed to suppress aberrant excitation of the auditory nerve that is thought to underlie the development of tinnitus.
There are no treatments approved for the disorder, but commonly used agents include oral corticosteroids, ginkgo biloba and benzodiazepines, as is masking by another stimulus. 84% of US ear, nose and throat physicians are dissatisfied with these, according to LifeSci Capital analysts.
If AM-101 succeeds it will hit a market ripe for disruption. But the signals so far have been mixed: a phase II trial failed to show a treatment benefit on its primary endpoint of minimal masking level – the lowest level at which the tinnitus can be masked by a stimulus – although it did hit other endpoints including tinnitus loudness (Upcoming events: MEI’s HDAC inhibitor data and futility from Auris in tinnitus, March 6, 2015).
AM-101 is also in a European trial, TACTT3, expected to report results in the fourth quarter. This has a similar design to TACTT2, but includes a second cohort evaluating patients with post-acute tinnitus between three and 12 months from onset.
Auris will likely wait until the TACTT3 data are available before filing the project with the FDA, Leerink analysts believe. They give it a 60% chance of success and put peak risk-adjusted sales at $350m.
LifeSci Capital analysts are more optimistic, saying the potential US market size for AM-101 is up to $630m. The acute form of the disease affects around 500,000 people in the US. The analysts note that the volume of patients could increase if an effective treatment becomes available.
Auris is also developing AM-111, which is in phase III for treating acute sensorineural hearing loss.