A Phase 2 Clinical Trial is a trial that is conducted to evaluate clinical efficacy of a drug for a particular condition in hundreds of patients and to determine the common short-term side effects and risks. A Phase 3 Clinical Trial is a larger trial in a wider variety of patients, which is needed to confirm the results before the regulatory authorities approve the drug for wider use. It is usual for more than one Phase 3 trial to be conducted to show how a potential drug works in a specific patient group.
The Company has concentrated on developing and testing its second-generation tau aggregation inhibitor (TAI) LMTX®, which has increased bioavailability and tolerability compared with its first-generation TAI rember®. This process required the completion of a number of preclinical toxicology studies as well as preclinical and clinical bridging studies required by the regulatory authorities.
The three Phase 3 clinical trials of LMTX® as described on this website have finished. While we have not started to recruit subjects for further clinical trials, we anticipate doing so later in 2017. We will place an announcement on the website when this process gets underway. If you or a relative are interested in participating in such trials, we suggest that you check our website from time to time for an announcement of trial recruitment.
TauRx’s drug rember®, a first-generation tau aggregation inhibitor (TAI), provided a potential breakthrough in disease treatment. Phase 2 clinical trial results provided the first evidence of a drug that substantially modified the Alzheimer’s neurodegenerative process (slowing down progression and halting further decline) rather than just treating the symptoms. Currently available prescription drugs treat symptoms by offering a transient boost to mental function, whereas rember® appeared to have the ability to halt decline in mental function for as long as the drug is taken. An improved version of rember®, TauRx’s second-generation TAI LMTX® is currently being evaluated in Phase 3 clinical trials. Only when all Phase 3 trials have been analysed will TauRx comment on the results as data analysis is still ongoing.
Current therapies for Alzheimer’s disease do not affect the progress of the disease itself, but only provide a temporary boost to mental function, with no long-term benefit. TauRx’s new approach is based on Tau Aggregation Inhibitors (TAIs), in which a drug acts on the abnormal tangles of tau protein that form in the brain cells of people with Alzheimer’s disease, and prevents them from forming. Importantly, the TauRx TAIs act on the early stage pre-tangle tau aggregates that are thought to have particular toxicity for nerve cells. To TauRx’s knowledge, no company other than TauRx has a TAI in later-stage clinical development. Data from Phase 3 clinical trials using TauRx’s second-generation TAI LMTX®, continue to support the possibility that LMTX® could be effective as monotherapy. One or more additional Phase 3 clinical trials are necessary to provide further data.
TAIs are the first treatments thought to attack an underlying cause of the disease rather than treating symptoms. In Alzheimer’s disease, tau tangles first destroy neurons critical for memory and then attack neurons in other parts of the brain as the tau aggregation process spreads from neuron to neuron throughout the brain. LMTX® works by preventing formation of the tangles that cause dementia. Tangles form first, and most severely, in the areas of the brain that are most critical for memory.
TauRx is currently investigating LMTX® in people with mild to moderate Alzheimer’s disease. Whilst both Phase 3 trials failed to meet primary endpoints, they did demonstrate promising results which warrant further investigation. Positive results were seen in a subgroup of patients from both Phase 3 trials who were on LMTX® monotherapy (i.e. taking no additional Alzheimer’s disease medications), and TauRx will need to investigate these specific findings further as the initial trial designs were not set out to test for this. The findings could be an exciting step forward.
The first-generation TAI rember® – the drug developed by scientists at the University of Aberdeen and tested in Phase 2 trials – is a new formulation of an existing chemical entity, but created especially for the treatment of neurodegenerative disease. LMTX® is the second-generation TAI, and has been the subject of the recent Phase 3 trials. The active ingredient in both drugs (methylthioninium, MT) is the same as that in an older chemical entity, methylthioninium chloride (MTC), which has been used in a variety of clinical indications for over a century. However, in the standard MTC form, the tolerability and bioavailability are limited meaning that it is unsuitable as the basis for chronic oral use. Patients and their care-givers should not source MTC themselves for use for Alzheimer’s disease as it is unlicensed for this indication.
It can be dangerous to buy any drug over the internet or from other sources. This is because you will not know what you are buying - it may not be pure and could be toxic and cause harm. TauRx’s proprietary TAIs have been specially created to be pure with good absorption and tolerability profiles at therapeutic doses and their properties will be guaranteed and regulated by the authorities.
Three Phase 3 studies are now completed and TauRx is planning further Phase 3 trials for LMTX® in Alzheimer's disease. If successful in future trials, LMTX® is likely to be the first TAI to come out of development. The clinical trials process, and subsequent regulatory approval processes, are long and rigorous to ensure that future therapies have been thoroughly proven to be safe and effective for patients before they are made available for use.
All drugs can cause side effects, and people taking LMTX® will be elderly and may have a number of other health conditions in addition to Alzheimer’s disease or frontotemporal dementia. Until the full Phase 3 study programme is complete, it is not possible to define the compound’s side effect profile. Preliminary safety findings can be found in the Lancet publication.
Three Phase 3 clinical trials of LMTX® as described on this website have finished. We are not recruiting patients for further clinical trials at this moment, but we anticipate doing so later in 2017. We will place an announcement on the website when this process gets underway. If you or a relative are interested in participating in such trials, we suggest that you check our website from time to time for an announcement of trial recruitment.
Your doctor will be unable to prescribe LMTX® for you, as it is unlicensed and is currently under investigation as a potential treatment for Alzheimer’s disease. Only when a drug has been approved by regulatory authorities and receives formal marketing authorisation can it be prescribed by physicians, as only then has it been deemed safe and effective for treatment. As always you should discuss any concerns about your health with your GP.
Only when the efficacy and safety of the drug have been confirmed in Phase 3 trials will the regulatory bodies give approval for the drug to be made generally available to the wider population.