Welcome to your weekly digest of approaching regulatory and clinical readouts. MEI Pharma expects topline phase II results on pracinostat as front-line treatment for myelodysplastic syndrome later this month, and as this, its lead pipeline asset, is unpartnered it will need to show impressive results to attract interest.
Also in the first quarter, Auris Medical is expected to release an interim futility analysis of a trial testing AM-101 in acute tinnitus. This will be the first look at phase III data for the project.
Pracinostat: MEI Pharma
Pracinostat is an oral HDAC inhibitor being tested in myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Approximately 30% of patients with MDS will go on to develop AML.
Topline data are expected in March from a phase II trial called MEI-003 testing pracinostat and Celgene's Vidaza versus placebo and Vidaza in 102 patients with previously untreated MDS. The primary endpoint is an efficacy estimate at six months measured by complete remission rate. Overall and progression-free survival are included in the secondary endpoints, and full data are expected at Asco in June.
In 2012 results from a 10-patient pilot study of pracinostat, again tested in combination with Vidaza, showed an overall response rate of 90% in advanced MDS, but it is difficult to draw meaningful conclusions from such a small trial.
At last year’s ASH conference the California-based company failed to excite the markets with a phase II pracinostat poster in AML. In combination with Vidaza 15 out of 33 patients achieved the primary endpoint of complete response; however, survival data are seen as the only clinically meaningful endpoint, and at the time shares fell 22%. Full topline data on 50 patients are expected in June.
The company intends to start phase III in first-line AML in June, recruiting 450 elderly patients and using overall survival as the endpoint. Analysts at Bank of America Merrill Lynch expect US launch for elderly AML patients in 2019, followed by MDS in 2020, noting that the MDS population is over twice as large as elderly AML. They model peak risk-adjusted US sales of $160m in 2026 for AML, and $460m in 2025 for MDS.
MEI acquired pracinostat in 2012 from S*Bio in 2012 for $500,000 in shares and milestone payments of up to $75.2 million. It has $79m in cash including $43m from an equity raise at the end of last year, which should fund operations through 2016, so it will likely need to raise more during phase III, or hope a bigger partner takes notice.
AM-101: Auris Medical
AM -101 blocks cochlear NMDA receptors to suppress aberrant excitation of the auditory nerve caused by injury or infection, resulting in high pitched ringing or hissing known commonly as tinnitus. It is Auris Medical’s lead asset and is in two phase III trials, one in North America called TACTT2 and one in Europe called TACTT3.
The upcoming interim futility data will be from the first 150 patients in the Stratum B arm of the European study. Stratum B aims to recruit a total of 300 patients with post-acute tinnitus – between three and 12 months from onset. Meanwhile Stratum A of the same trial will include 300 patients with acute tinnitus – up to three months from onset.
The US study TACTT2 intends to recruit 330 patients in the acute stage only. Topline efficacy data from the trials are expected next year and will be measured by patient reported outcomes. Both studies are running under a special protocol assessment, and AM-101 will be administered by intratympanic injection into the middle ear.
Past clinical results have been mixed. A phase II trial failed to show a treatment benefit for the primary endpoint of minimal masking level, defined as the lowest level at which the tinnitus can be masked by a stimulus.
The study tested AM-101 in 248 patients with persistent acute tinnitus after noise trauma, idiopathic sudden sensorineural hearing loss (ISSNHL), or acute otitis media, an ear infection.
AM-101 was statistically better than placebo in patient-reported outcomes such as tinnitus loudness, annoyance, sleep difficulties, and impact in patients with tinnitus after noise trauma or otitis media. In the ISSNHL subgroup the results were inconclusive.
The Swiss company completed its $65m Nasdaq IPO last August. It floated at a 45% discount to the intended filed price, and shares have been stagnant to date. As AM-101 is its lead asset investors will be looking for it to improve sentiment.
|Pracinostat||MEI-003 (untreated MDS)
MEI-004 (elderly AML)
MEI-005 (refractory MDS)
|AM-101||TACTT2 (North America)