Clinical Trial Frequently Asked Questions
TauRx reported rember® Phase 2 results in 2008. What has the company been doing since then?
TauRx has made significant R&D, infrastructural and commercial advancements since 2008. On the R&D side, TauRx has discovered and is developing alternative Tau Aggregation Inhibitors (TAIs) as second -generation forms of the same active moiety present in rember®. These have been chemically optimized to have enhanced tolerability and bioavailability, enabling their use at higher doses than rember®. TauRx’s TAIs are backed by a robust patent estate.
TauRx’s lead second-generation TAI, LMTX™, is now under investigation in clinical trials conducted under an open US IND. The results of these trials and those of a range of supportive preclinical studies are so promising that LMTX™ has been prioritized as a replacement for rember® in our Phase 3 clinical program. Under a development plan agreed with US and EU regulatory authorities, we are now evaluating LMTX™ in pivotal international Phase 3 trials in mild and moderate AD and related neurodegenerative diseases.
Structurally, TauRx has enhanced its R&D and commercial expertise with numerous appointments. Also, we will shortly announce the appointment of several internationally recognized scientists in the field of neurodegenerative diseases to our Scientific Advisory Board.
Lastly, but importantly, we have also conducted a preliminary clinical study using rember® in patients diagnosed with Frontotemporal dementia (FTD) with promising results. FTD is one of several lethal neurodegenerative diseases characterised by the formation of Tau aggregates for which no treatments are available. A pivotal clinical trial has started in FTD and we hope to expand our clinical development projects to include a second Tau aggregate related disease. Due to the classification of FTD and the additional diseases we are considering as orphan indications, provisions agreed by the US and European regulatory authorities permit fast-tracked regulatory reviews and marketing approvals in orphan diseases where disease prevalence is low and there is a compelling medical need.
How big a breakthrough are TauRx’s drugs?
TauRx’s drug rember®, a Tau Aggregation Inhibitor (TAI), is a breakthrough. Phase 2 clinical trial results showed the first evidence of a drug that actually modified the Alzheimer’s process (slowing down progression and halting further decline) rather than just treating the symptoms. Currently available prescription drugs treat symptoms only by offering a temporary boost to mental function, whereas rember® continues to halt decline in mental function for as long as the drug is taken. Because of what we know about the correlation of the accumulation of Tau Aggregates with the onset of Alzheimer’s disease, there is a strong potential that TAIs could actually stop or even prevent disease if given at an early enough point in the disease process.
How are TauRx’s drugs new/different to what is already available for Alzheimer’s?
Current therapies for Alzheimer’s 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 rember® trial was the first successful trial of a new approach, in which a drug acts on the abnormal tangles of Tau protein that form in the brain cells of people with Alzheimer’s, and disrupts and ‘dissolves’ them. More importantly our TAIs act on the early stage pre-tangle aggregates that are thought to have particular toxicity for nerve cells. To our knowledge, no company other than TauRx has a TAI in preclinical or clinical development, although there is an increasing research momentum by discovery groups following TauRx’s lead, particularly given the failures of the amyloid-based approaches to date. However, the long time-frame required for clinical trials in Alzheimer’s means that these programs are unlikely to reach the market until after 2020.
Could TAIs be the magic bullet/miracle cure for Alzheimer’s? When will the Phase 3 trials begin?
The rember® results from our Phase 2 trial are exciting and encouraging, and we are now conducting two Phase 3 trials to confirm these results in people with mild and moderate AD. We will then seek to make this drug available as soon as possible for people in the mild to moderate stage of the disease.
At the same time we are conducting more research to investigate the future potential of this approach and type of drug - to find out if we can actually reverse the disease at the milder stages of the disease. Then we want to ultimately prevent it from occurring in the first place. That is the ultimate goal of TauRx and one that would have enormous benefit for millions of families worldwide, in addition to huge cost savings for national economies and health services.
Does it work on everyone with Alzheimer's?
Our Phase 2 trial tested the drug in over 300 people with mild or moderate Alzheimer's and found these encouraging results. We do not have any evidence that the drug could dissolve the tangles in the brain of a person with advanced Alzheimer's in which many nerve cells will already have been destroyed. This will form part of our ongoing research.
How do TauRx’s TAIs work?
The drugs appear to be able to disrupt and ‘dissolve’ the tangles of Tau protein which form abnormal ‘aggregates’ in the brain cells of people with Alzheimer’s and ultimately destroy the cells. More importantly our TAIs act on the early stage pre-tangle Tau aggregates (“oligomers”) that are thought to be particularly toxic to nerve cells. We know that these tangles form earliest and most severely in the areas of the brain that are most critical for memory, and we have seen from the brain scans of people exposed to our TAIs during our Phase 2 trial that these are the very areas of the brain where rember® appeared to have the greatest effect in protecting against ongoing loss of neuronal function.
At what stage could people with Alzheimer’s take TAIs?
It is known that disease-related changes to the Tau protein can appear as much as 20 years before the onset of symptoms. Given these timings and the action of TAIs as demonstrated in our research studies and clinical trials, we have strong hopes that further breakthroughs in the management of AD are possible. The combination of a diagnostic, such as we are developing in a collaborative project, and a disease modifying or preventative drug has the potential to identify susceptible individuals and prevent the development of AD. Our Phase 2 clinical trial in patients with mild and moderate severity AD demonstrated potential utility in these patient populations (to be confirmed in the upcoming Phase 3 trials). It is unclear if TAIs would have utility in patients with advanced disease wherein significant neuronal damage and cell death had already occurred. All these categories of drug use are being studied at TauRx.
How did the people on the rember® trial improve?
Every person is unique, and Alzheimer’s affects people in varying ways. However people in the rember® trial reported that they felt more confident and better able to cope with daily life, and did not experience the same degree of mental decline that they and their carers had expected. In terms of clinical readouts, rember® showed evidence in the Phase 2 trial of a significant reduction in the rate of clinical decline: 80% by weeks 50 and 102 of this trial, relative to controls, as measured using psychometric tools. Functional neuroimaging results from the trial supported the psychometric data: in patients exposed to rember®, the loss of function occurring in the areas of the brain known to be particularly affected by the Tau-tangle pathology of the disease was eliminated over 6 months.
What are Phase 2 and Phase 3 clinical trials?
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.
Are TAIs new drugs?
rember®, our first-generation TAI and the drug developed by scientists at the University of Aberdeen and tested in Phase 2 trials, is a new version of an existing drug, but created especially for the treatment of AD. We have patented it for use in Alzheimer’s disease. As described above, TauRx has recently brought a number of proprietary second-generation TAIs into development. One of these, LMTX™, has been prioritised ahead of rember® due to its superior tolerability and bioavailability profile as described in the above. The active ingredient in these compounds (methylthioninium, MT) is the same as an old drug existing as the chloride salt (MTC), which has been used in a variety of clinical indications for over a century. However, in the MTC form, the tolerability and bioavailability is limited. People should avoid sourcing MTC themselves for use for Alzheimer’s as it may not be pure and could prove harmful. In addition, the effective dosing range is limited by side effects and tolerability. This is why TauRx has developed LMTX™ which has been optimised for improved bioavailability and tolerability.
Can I buy MTC over the internet?
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.
When will TAIs be available?
We need to complete Phase 3 trials to confirm the therapeutic and tolerability profile of our TAI, LMTX™, on a still larger scale, and to further refine this treatment. If these trials are successful, the company will apply to the appropriate regulatory bodies for authorisation to market LMTX™ as a regulated and approved treatment for mild to moderate Alzheimer’s and one or more orphan indications.
Do TAIs and LMTX™ in particular have any side effects?
All drugs can cause side effects in some people, and people taking LMTX™ will be elderly and have a number of other health conditions in addition to Alzheimer’s. However the evidence is that rember® was generally well tolerated, although the dosing range was limited in terms of tolerability and side effects, leading to limitation in the maximum potential efficacy. The emerging data on LMTX™ indicates that TauRx’s second generation TAI has an especially good tolerability profile allowing dosing at higher levels and so possibly achieving better efficacy than the already striking effects seen with rember® in the previously reported Phase 2 trial. A feature of TauRx’s lead TAIs is that they discolour urine and this can cause staining which some people find distressing.
How can I/my relative get on a trial?
Phase 3 trials involving clinical teams in many countries including Europe and the US are underway and this website provides information on study involvement. It is up to the doctors in the clinical centres taking part in the study to select patients who would be suitable for the trial and explain to them what is involved. People cannot offer themselves or their relatives for the trial directly to TauRx.
Can I ask my doctor for this now?
Your doctor will be unable to prescribe this for you at the present time, as the drug cannot be approved by the regulatory bodies until we have confirmatory results from Phase 3 trials. In the meantime you are advised not to try to buy MTC over the internet or from other unapproved sources, since there will be no guarantee of purity and it could cause harm. As always you should discuss any concerns about your health with your GP.
Why can’t this be available now?
A Phase 3 trial is necessary to confirm the promising benefits of the drug we saw in Phase 2, and further refine the treatment. Only when the efficacy and safety of the drug have been confirmed will the regulatory bodies give approval for the drug to be made generally available to the wider population.