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The <a href="https://www.als.org/">ALS Association</a> is partnering with <a href="https://mytomorrows.com/">MyTomorrows</a>, a global health technology company, to make it easier for people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) to find and participate in clinical trials, and to know about &#8220;pre-approval treatment options,&#8221; the company said in a <a href="https://mytomorrows.com/blog/partnership/mytomorrows-partners-with-the-als-association-to-support-als-patients-in-accessing-clinical-trials/">press release</a>.
The collaboration will allow the nonprofit to tap into the company&#8217;s database of ongoing clinical trials — granting treating physicians, patients, and families access to information about experimental treatment options in ALS and guiding them toward relevant studies.
&#8220;We look forward to witnessing the impact of our partnership with the ALS Association, one of the most effective and impactful patient advocacy groups in the United States,&#8221; said Michel van Harten, MD, myTomorrows’ CEO, who noted the &#8220;high unmet needs&#8221; of ALS patients.
“Partnering with leading patient advocacy groups such as the ALS Association will help an even larger cohort of ALS patients and their treating physicians discover clinical trials, thereby reducing the barriers they may face in accessing their treatment options,&#8221; van Harten added.
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<h3>Collaboration to make use of myTomorrows digital platform</h3>
ALS is caused by the progressive dysfunction and death of motor neurons, the nerve cells that control voluntary movements. This results in progressive muscle weakness, with <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a> such as trouble walking, and difficulty speaking, swallowing, and breathing.
Because ALS has such a great impact on a person&#8217;s everyday life and typically progresses at a fast rate, searching for clinical trials that patients can get involved in is a particularly difficult task, according to myTomorrows.
The company offers a digital platform that connects pharmaceutical companies and trial sites with physicians and patients — conducting extensive searches of databases worldwide to provide up-to-date information on available experimental treatments and clinical trials.
Providing patient and clinician access to such information will be helpful for the pharmaceutical companies developing novel ALS therapies, according to myTomorrows, which noted that treatment developers commonly face struggles in patient recruitment.
The longer these trials take to enroll their target number of participants, the greater the delay in treatment development and the longer it will take to bring these treatments to the market, the company noted.
&#8220;myTomorrows explores each patient’s case individually, helping ALS patients and their loved ones identify and understand all of the available clinical trial options in a well-rounded manner, guided by expert patient navigators,&#8221; the release states.
The goal, according to the company, is to help patients and their physicians to be aware of treatment options and make informed decisions on the best treatment journey.
[quote=&#8221;center&#8221;]Research participation is so impactful to finding treatments and cures as well as reducing the harms of ALS.[/quote]
The company also provides information on international expanded access programs, which allow patients who fail to qualify for clinical trials to in some cases get access to an investigational therapy.
Pam Knott, the ALS Association’s vice president of data and technology, said the nonprofit is &#8220;very excited about this new partnership.&#8221;
&#8220;Research participation is so impactful to finding treatments and cures as well as reducing the harms of ALS,&#8221; Knott said. She added that the collaboration is &#8220;an opportunity to allow more people with ALS to enroll in clinical trials faster while also reducing burden.&#8221;
The ALS Association serves more than 20,000 people living with ALS in the U.S. The nonprofit organization raises awareness of the disease, provides funding to support research and development of new treatments and clinical trials, and offers care services for both patients and caregivers.

ALS Association, myTomorrows team up to aid clinical trial access

The technology company <a href="https://www.unlearn.ai/">Unlearn</a> has joined with <a href="https://quralis.com/">QurAlis</a> to use artificial intelligence (AI) to speed up clinincal trials for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The aim of the collaboration is to minimize variability and increase the statistical strength of QurAlis&#8217; clinical trials that are evaluating their primary ALS therapeutic candidates, QRL-201 and QRL-101.
&#8220;We are excited to partner with Unlearn to help advance our clinical program with AI and other innovative technologies to generate evidence suitable for supporting regulatory decisions and help speed new, lifesaving precision medicines to patients with ALS and other neurodegenerative diseases,&#8221; Kasper Roet, PhD, QurAlis&#8217; founder and CEO, said in a <a href="https://www.prnewswire.com/news-releases/quralis-and-unlearn-announce-collaboration-to-accelerate-and-optimize-als-clinical-trials-with-generative-artificial-intelligence-technologies-301863473.html">company press release</a>.
Unlearn uses an AI technique called machine learning to create &#8220;digital twins&#8221; of patients enrolled in clinical trials. Its patented machine learning models are trained on large volumes of completed clinical data and can predict, at the individual level, the outcomes of these digital twins if they were given the control treatment.
Data collected from each patient is fed to the AI model to generate a digital twin, which will be utilized in randomized controlled trials (RCTs) called <a href="https://www.unlearn.ai/twinrcts">TwinRCTs</a>.
TwinRCTs are designed to provide more statistical power with smaller control groups than traditional trial designs. Many patients are wary of enrolling in clinical trials because they might receive a placebo, but a smaller control group boosts the chance of getting the investigational treatment.
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<h3>Benefits of using AI in ALS clinical trials</h3>
The technology will also speed up a trial&#8217;s enrollment process, accelerating a therapy&#8217;s time to market.
&#8220;By using machine learning to leverage the wealth of existing patient data from completed clinical trials, our technology significantly shortens typical timelines by months while generating evidence suitable for supporting regulatory decisions,&#8221; said Charles Fisher, PhD, Unlearn&#8217;s founder and CEO.
At the end of the trial, outcome scores derived from the digital twins will be integrated into the primary trial analysis. This will allow for an accurate estimate of treatment effects and minimize false positives (Type-1 errors), a result that indicates a treatment&#8217;s effectiveness.
&#8220;Advances in machine learning and AI make it possible to enhance trial power to detect a positive result when one truly exists while controlling for Type-1 error and significantly shorten timelines without introducing bias into the study,&#8221; Roet said.
The technology will be used to accelerate the development of QRL-201, a treatment designed to raise stathmin-2 levels and lower the toxic TDP-43 clumps that build up and damage nerve cells in ALS.
It will also boost clinical trials of QRL-101, which is designed to reduce the excessive firing of electrical signals, known as hyperexcitability, seen in about half of ALS cases.
QRL-201 is being investigated in a Phase 1 clinical trial called <a href="https://www.clinicaltrials.gov/ct2/show/NCT05633459">ANQUR (NCT05633459)</a>, which recently <a href="https://alsnewstoday.com/news/dosing-phase-1-clinical-trial-als-qrl-201-protect-neurons/">dosed its first patient</a>. The study is testing the tolerability and safety of ascending doses against a placebo in up to 64 adults with ALS without SOD1 or FUS gene mutations.
The trial is ongoing in Canada and U.S. sites are expected to open soon. QurAlis anticipates <a href="https://alsnewstoday.com/news/phase-1-trial-experimental-als-treatment-qrl-201-opening-eu/">sites in the European Union</a> by the end of the year.
QRL-101 is also undergoing clinical testing in a <a href="https://clinicaltrials.gov/ct2/show/NCT05667779?term=NCT05667779&amp;draw=2&amp;rank=1#contacts">Phase 1 trial (NCT05667779)</a>. The study, which <a href="https://alsnewstoday.com/news/first-participants-dosed-phase-1-trial-als-therapy-qrl-101/">began dosing this year</a>, will assess the therapy&#8217;s safety, tolerability, and pharmacological properties in up to 40 healthy adults at a single center in the Netherlands.
&#8220;The AI technology we&#8217;re developing today will revolutionize the future of clinical research,&#8221; Fisher said.

QurAlis teaming with Unlearn to use AI to improve ALS clinical trials

Difficulties in measuring the progression of <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) among patients with advanced disease can cause complications in clinical trials, according to a new analysis that highlights how such problems may have affected the failed <a href="https://alsnewstoday.com/nurown/">NurOwn</a> study.
The work was led by scientists at <a href="https://brainstorm-cell.com/" rel="nofollow">BrainStorm Cell Therapeutics</a>, which is developing the cell therapy NurOwn as a potential treatment for ALS.
Late last year, the U.S. Food and Drug Administration (FDA) <a href="https://alsnewstoday.com/news/fda-declines-considering-nurown-als/">declined to consider</a> an application from BrainStorm seeking NurOwn&#8217;s approval. The company now is working to identify the <a href="https://alsnewstoday.com/news/fda-grants-jan-11-meeting-discuss-nurown-future-als-brainstorm/">next steps</a> for the experimental therapy.
The findings of the new analysis were shared at the recent Muscular Dystrophy Association&#8217;s MDA Clinical &amp; Scientific Conference, in a poster titled &#8220;<a href="https://www.mdaconference.org/abstract-library/measuring-the-rate-of-impairment-in-als-patients-using-the-revised-als-functional-rating-scale-key-insights-into-the-floor-effect-of-the-scale/">Measuring the rate of impairment in ALS patients using the Revised-ALS Functional Rating Scale: Key Insights into the Floor Effect of the Scale</a>.&#8221;
&#8220;While widely used, the [current] scale is hampered by its ability to measure function in those with low functional status,&#8221; such as individuals with advanced disease, the researchers wrote.
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<h3>More than 20% of patients in NurOwn trial had low ALSFRS-R scores</h3>
NurOwn is a cell-based therapy in which mesenchymal stem cells — cells with the capacity to transform into a variety of cell types — are isolated from the bone marrow and matured in the lab to produce large amounts of signaling molecules that promote nerve cell survival and growth.
As part of the treatment&#8217;s development, BrainStorm had conducted a <a href="https://clinicaltrials.gov/ct2/show/NCT03280056">Phase 3 clinical trial (NCT03280056)</a> to test NurOwn against a placebo in people with fast-progressing ALS. Completed in 2020, that trial involved 189 patients, ages 18-60. Its main goal was to test whether the treatment could slow the progression of ALS symptoms.
The trial, however, <a href="https://alsnewstoday.com/news/nurown-fails-to-slow-disease-progression-in-als-patients-top-line-data-show/">failed to meet this goal</a>: the rate of progression was not significantly different between patients given NurOwn or a placebo.
Like many ALS trials, that Phase 3 study of NurOwn used a measure of disease progression called the ALS Functional Rating Scale-Revised (ALSFRS-R).
This scale assigns numeric scores to a patient&#8217;s ability to function across several categories, from swallowing to turning in bed, which are then added to calculate the total score. Higher scores reflect a better ability to function, and scores tend to decrease as ALS progresses and patients lose functional abilities.
In the MDA poster, researchers highlighted that the ALSFRS-R is subject to a so-called floor effect: once a particular measure has reached zero, it can&#8217;t go any lower, even if the patient is continuing to lose functionality. As a result, ALSFRS-R scores can plateau or stabilize in patients with advanced disease, failing to reflect the progression that the patient is actually experiencing.
Through statistical analyses, the researchers showed that more than 1 in 5 patients (22.3%) given a placebo in the Phase 3 trial exhibited a floor effect — ALSFRS-R scores specifically tended to plateau around 27 points.
[quote align=&#8221;center&#8221;]For future trials, these data suggest requiring ALSFRS-R items be at least 2 or seeking a more suitable measure for patients with advanced ALS.[/quote]
Analyses of data for nearly 4,000 ALS patients from a large database called PRO-ACT showed that nearly 5% of patients exhibited a similar floor effect, usually around 25 points on the ALSFRS-R, suggesting that this issue is not unique to the NurOwn trial.
Floor effects were most common among patients who started off with lower ALSFRS-R scores. The researchers noted that the average starting ALSFRS-R score in the NurOwn trial was less than 32 points, which is markedly lower than for other modern ALS trials, where average scores have been 36 or higher.
The researchers then re-analyzed data from the NurOwn trial, but assessing only data for the 106 patients who did not show any signs of a floor effect at the start of the study. Results showed that, over the course of the six-month Phase 3 study, the average decline in ALSFRS-R scores was 2.68 for patients given NurOwn and 4.99 for patients given a placebo.
&#8220;Analyses conducted on those not impacted by the floor &#8230; reveal statistically significant, clinically meaningful treatment effects with NurOwn,&#8221; the researchers wrote.
To prevent issues with the floor effect in future trials that use the ALSFRS-R, the researchers suggested that it may be beneficial to limit studies to only patients who have a score of at least 2 on all parts of the ALSFRS-R.
&#8220;For future trials, these data suggest requiring ALSFRS-R items be at least 2 or seeking a more suitable measure for patients with advanced ALS,&#8221; the team wrote.

Tag: clinical trials

ALS Association, myTomorrows team up to aid clinical trial access

QurAlis teaming with Unlearn to use AI to improve ALS clinical trials

MDA 2023: Issues with ALS scale scores noted in NurOwn trial failure