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<a href="https://alsnewstoday.com/what-is-als/">ALS</a> was <a href="https://www.als.org/understanding-als">first identified</a> in 1869, though its <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a> were <a href="https://www.pharmaceutical-technology.com/features/history-of-als/?cf-view">documented</a> in medical literature as early as 1824. It&#8217;s intriguing that the sequence of the disease today is often similar, with initial symptoms followed by an actual diagnosis.
It took four years to receive my <a href="https://alsnewstoday.com/als-diagnosis/">diagnosis of ALS</a>, during which time I went through <a href="https://alsnewstoday.com/columns/physical-occupational-therapy-improve-quality-life-als/">physical therapy</a>, chiropractic manipulation, myriad tests for <a href="https://parkinsonsnewstoday.com/what-is-parkinsons-disease/">Parkinson&#8217;s</a> and other illnesses, and back surgery. The <a href="https://alsnewstoday.com/living-with-als-2/">reality of ALS</a> is fraught with issues that relate to its onset typically occurring months or years before a diagnosis. In other words, there&#8217;s <a href="https://www.als.org/understanding-als/symptoms-diagnosis">no definitive way</a> to &#8220;catch it early.&#8221;
Some conditions, such as certain types of cancer, can be headed off if caught early. But many rare, degenerative diseases cannot be detected early, and even if they could, the prognosis is always the same. No remission and no dormancy. So what can we do?
[recommended-reading id=90697]
<h3>Bringing ALS to the forefront</h3>
I understand the economics of medical research and drug development aren&#8217;t conducive to dedicating much time to finding a cure for ALS. But I also understand and believe in the squeaky-wheel concept. Thus, we have to squeak much louder.
There&#8217;s a relatively small cadre of dedicated persons, medical, legal, and political, who work tirelessly to find and advocate for solutions to ease the burdens borne by ALS victims and their families. But they need help.
The way things are in our slow-paced world of drug approvals and research initiatives, those who contract ALS today have little hope they&#8217;ll see a cure or a cessation of symptoms.
As I&#8217;ve said before, <a href="https://alsnewstoday.com/columns/living-my-life-key-d-minor/">miracles do exist</a>. But I also believe we need more miracle makers and miracle assistants. One such person is Michelle Lorenz, whom I met online a few years ago and worked with to get senators to support the fast-tracking of an <a href="https://www.congress.gov/bill/117th-congress/house-bill/3537">initiative</a> to help suppress ALS.
Michelle is indefatigable and relentless when it comes to lobbying for the rights and <a href="https://alsnewstoday.com/approved-treatments-for-als/">treatment</a> of ALS patients. Check her out on <a href="https://www.facebook.com/michelle.lorenz.395">Facebook</a>.
It&#8217;s unimaginable that diagnosis — and thus, treatment — for one of the worst diseases known to man can take four years, as it did for me. This is not 1824 or 1869. Surely we can do better.
One of the most disquieting things for me is hearing about a younger person or a friend being diagnosed with ALS. It truly makes me sad, and recently I received news of both. I wish I had that proverbial magic wand to make it all go away or make it better.
It&#8217;s also very disheartening to hear about <a href="https://alsnewstoday.com/forms-of-als-familial-als/">familial ALS</a> cases. <a href="https://alsnewstoday.com/columns/how-familial-als-shaped-friends-journey/">I wrote about one family in a previous column</a>, and a reader shared that her family has also lost several members to ALS.
On a positive note, I just received some news of progress on the familial type. Last month, the <a href="https://www.msn.com/en-us/health/other/accumulation-of-junk-proteins-identified-as-one-cause-of-aging-and-possible-source-of-als/ar-BB1kmg6q">Spanish National Cancer Research Center</a> noted that a paper published in Molecular Cell &#8220;provides the first evidence that a possible cause of the hereditary type of ALS — familial ALS — is the accumulation in motor neurons of &#8216;junk proteins,&#8217; proteins with no function that wrongly accumulate and prevent the cell from functioning properly.&#8221; According to researchers, this finding could help them explore new treatment pathways.
We who have suffered for years — and know how hard ALS is — are deeply hurt by new cases, especially when a young person gets our disease. And knowing that anyone can get it, we encourage all who can to do all they can to put an end to this heinous condition.
Simply because a disease is rare doesn&#8217;t justify putting it on the back burner. We must give more of our time, talent, and treasure to the diagnosis, treatment, and cure for ALS. We owe it to our society.
<hr />
Note: <a href="https://alsnewstoday.com/">ALS News Today</a> is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of ALS News Today or its parent company, BioNews, and are intended to spark discussion about issues pertaining to ALS.

We must do more to accelerate the diagnosis and treatment of ALS

Two Canadian provinces — Prince Edward Island, and Newfoundland and Labrador — are covering the cost of the oral formulation of <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava</a> (edaravone) for eligible residents with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
Patients will have access through their provincial drug plans to <a href="https://alsnewstoday.com/radicava-edaravone-for-als/#Indications">Radicava Oral Suspension</a>, developed along with the infusion formulation by <a href="https://www.mt-pharma.co.jp/e/" rel="nofollow">Mitsubishi Tanabe Pharma</a>. The medication will be covered by special authorization under the PEI Pharmacare Formulary as well as the Newfoundland and Labrador Prescription Drug Program.
Residents typically have <a href="https://www.gov.nl.ca/hcs/prescription/nlpdp-plan-overview/">a medicine copay</a>, usually a small fee, to cover on their own.
&#8220;We would like to thank the Governments of Prince Edward Island and Newfoundland and Labrador for supporting eligible patients living with ALS to have publicly funded access to Radicava Oral Suspension,&#8221; Andy Zylak, president of Mitsubishi Tanabe Pharma Canada (MTP-CA), said in a <a href="https://www.newswire.ca/news-releases/mitsubishi-tanabe-pharma-canada-announces-that-company-s-oral-treatment-formulation-for-amyotrophic-lateral-sclerosis-als-has-been-added-to-the-provincial-drug-plans-in-prince-edward-island-newfoundland-and-labrador-810205320.html">company press release</a>.
[recommended-reading id=87664]
<h3>Oral formulation of Radicava seen as more convenient ALS treatment option</h3>
MTP-CA is a subsidiary of <a href="https://www.mt-pharma-america.com/" rel="nofollow">Mitsubishi Tanabe Pharma America</a>, which commercializes Radicava formulations in the U.S. There, the oral therapy is sold under the brand name Radicava ORS.
&#8220;To date, Radicava Oral Suspension is listed on the majority of provincial public drug plans. MTP-CA will continue to work with the remaining provincial, territorial and federal drug plans to help ensure that Radicava Oral Suspension is listed on all public formularies across the country,&#8221; Zylak added.
Edaravone, the active ingredient in both the oral and infusion therapies, is a free radical scavenger that helps to clear the body of the reactive molecules that can led to oxidative stress, a type of damage implicated in ALS. Their removal is expected to lessen the motor neuron damage that causes <a href="https://alsnewstoday.com/symptoms-of-als/">muscle weakness and other ALS symptoms</a>, helping to slow disease progression.
An intravenous formulation of Radicava was <a href="https://alsnewstoday.com/news/radicava-now-approved-to-treat-als-patients-in-canada/">approved in Canada in 2018</a>, becoming the first new ALS therapy available in the country in about 20 years. It is covered across Canadian provinces and territories, as well as through Veterans Affairs Canada and Indigenous Services Canada.
Health Canada <a href="https://alsnewstoday.com/news/radicava-oral-suspension-approved-canada-treat-als/">approved Radicava Oral Suspension</a> in 2022, providing ALS patients with a treatment seen as an easier, more convenient alternative to the infusion therapy. In addition to the two latest provinces, Radicava&#8217;s oral formulation is listed on public drug plans of Ontario, Quebec, Alberta, British Columbia, New Brunswick, Saskatchewan, and Nova Scotia.
&#8220;Access to new treatments plays a key role in helping people and their families live their best possible life in the face of an <a href="https://alsnewstoday.com/als-diagnosis/">ALS diagnosis</a>,&#8221; said Kathy MacNeill, past president of the ALS Society of Prince Edward Island.
According to MTP-CA, most private health insurance plans in the country also cover the oral medication.
&#8220;People living with ALS do not have the luxury of time to wait for access to new medications to slow the progression of their disease,&#8221; said Cheryl Power, executive director of the ALS Society of Newfoundland and Labrador. &#8220;For this reason, we&#8217;re pleased that people impacted by ALS in this province will now have publicly funded access to Radicava Oral Suspension.&#8221;

Radicava Oral Suspension added to drug plans of 2 Canadian provinces

People with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) report significant changes in lifestyle after their diagnosis, but still have an acceptable quality of life and low stress levels, according to a survey conducted across nine European countries.
When asked about new drug development, participants most commonly prioritized <a href="https://alsnewstoday.com/approved-treatments-for-als/">treatments</a> that slow disease progression or help with breathing or mobility. Also, there may be a need to better educate patients about the scales used to monitor disease progression or certain <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a>.
The study, “<a href="https://www.tandfonline.com/doi/abs/10.1080/21678421.2023.2249515">IMPACT-ALS: summary of results from a European survey of people living with ALS</a>,” was published in the journal <a href="https://www.tandfonline.com/journals/iafd20">Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration</a>.
The majority of scales used to monitor people with ALS tend to focus more on the clinical aspect of the disease, such as the motor symptoms it causes and how fast the disease is progressing. But the actual patient experience is often left out.
Thus, to better understand the functional burden of ALS and ensure that patient experiences contribute to the development of novel therapies, researchers developed the IMPACT-ALS European survey.
The survey collected the experiences of people <a href="https://alsnewstoday.com/living-with-als-2/">living with ALS</a> across nine European countries participating in the <a href="https://www.encals.eu/">European Network to Cure of ALS</a>: United Kingdom, Ireland, Germany, France, Spain, Italy, Belgium, Netherlands, and Sweden.
It involved similar questions from a previous U.S. IMPACT-ALS survey, which were adapted and translated into the main languages of the participating countries.
[recommended-reading id=84549]
<h3>Questionnaire covered demographics, treatments, living with ALS</h3>
The questionnaire included 36 questions grouped in four sections. The first group of questions collected data regarding demographics such as age, gender, employment, marital status, education, and country of residence. The second and third collected information about the disease and treatments, and the fourth was focused on living with ALS, including recent symptoms, fears, and stress levels.
A total of 857 patients, mostly men (57%), responded to the survey. The majority of responses were from Italy, and participation rates ranged from 0.2%-6.3% based on ALS prevalence in each country. About two-thirds of patients were in the 55-74 age range.
In total, 91% of participants answered questions regarding their symptoms and <a href="https://alsnewstoday.com/als-diagnosis/">ALS diagnosis</a>. In half, the first symptoms had appeared two to three years before the survey and the formal diagnosis had been issued 1.5-2 years earlier. The most common first symptom was weakness in the arms or legs (60%), followed by falling and speech problems.
About two-thirds knew which <a href="https://alsnewstoday.com/forms-of-als/">ALS type</a> they had: 58% of patients had <a href="https://alsnewstoday.com/sporadic-als/">sporadic ALS</a> and 6.4% <a href="https://alsnewstoday.com/forms-of-als-familial-als/">familial ALS</a>, while 35% who did not know their disease form.
Also, while genetic testing <a href="https://alsnewstoday.com/news/genetic-test-als-all-patients-guidelines/">is now recommended</a> for all with the neurodegenerative condition, less than half of the respondents underwent such testing. The most frequent mutations were detected in the SOD1 (15%) and C9orf72 (24%) genes.
More than half of patients did not know about the ALS Functional Rating Scale &#8211; Revised (ALSFRS-R), the researchers noted. This is a validated measure of disease progression that essentially assesses a person&#8217;s ability to perform activities of daily living such as buttoning a shirt, grabbing a pen, turning in bed, or speaking clearly.
For the patients who knew their ALSFRS-R score, the median score was higher — indicating less severe disease and a greater ability to perform daily functions — among patients with the most recent diagnosis than in those with a longer-established diagnosis (37 vs. 31).
<h3>ALS symptoms included fatigue, speech issues, depression</h3>
In the two weeks preceding the survey, the most common symptoms were limb weakness, fatigue, and <a href="https://alsnewstoday.com/speech-problems/">speech problems</a>. Other symptoms such as pain, <a href="https://alsnewstoday.com/als-mental-health/">depression or mood changes</a>, apathy, and thinking difficulties were also present in at least 1 in 10 patients.
Patients also often reported issues with physical activities in that period, such as trouble walking (67%), difficulty managing buttons or keys (64%), or problems rising from a chair (62%).
Still, most patients reported low to medium levels of stress in the two weeks prior to the survey and moderate quality of life in the two days prior.
There were certain fears related to the future in about 82% of patients, although fear was less common in people diagnosed for longer (75.3%). The most common fears were leaving family too soon, dying from respiratory failure, having an injury, needing invasive ventilation, or experiencing social isolation due to communication impairments.
Participants also reported changes in their life since the diagnosis. In general, they spent less time on most daily activities, and more on the internet, reading, and communicating with family and friends.
<h3>Treatment options detailed</h3>
In terms of treatment, 12% required a feeding tube and 22% needed noninvasive ventilatory support. For mobility, more than half attended physical therapy, about one-third did regular exercise, and some required manual or motorized wheelchairs or wheeled walkers.
When asked about what they valued more about current and new treatments, most patients wanted therapies that could stop disease progression. Other treatments that were highly sought were those that could improve breathing and mobility.
“To enable the delivery of care that meets the needs of [people with ALS], further work is required to focus on commonly reported symptoms as well as those symptoms which patients want treating the most,” the researchers wrote. “The findings we report from this survey support the increased use of [patient-reported outcome measures] in clinical trials to promote the development of patient focused interventions to improve quality of life.”

Survey offers look at life, treatment priorities of those living with ALS

In a nearly unanimous vote, an advisory committee to the U.S. Food and Drug Administration (FDA) said there&#8217;s not enough evidence to support the efficacy of the experimental stem cell therapy <a href="https://alsnewstoday.com/nurown/">NurOwn</a> as a treatment for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The committee voted on a single question in its meeting: &#8220;Do the data presented demonstrate substantial evidence of effectiveness for treatment of mild to moderate ALS?&#8221;
In all, 17 of the 19 committee members voted no. There was one yes vote and one abstention.
An <a href="https://alsnewstoday.com/news/fda-final-approval-decision-brainstorms-nurown-als-due-december/">official decision from the FDA</a> on NurOwn is set to be handed down in December. The regulatory agency is not obligated to abide by the committee&#8217;s vote, but it usually does.
&#8220;The discussion in today&#8217;s advisory committee meeting, and the heartrending testimony of those living with ALS and their loved ones, underscores not only the need for regulatory flexibility but also for continuing research in the field,&#8221; Chaim Lebovits, president and CEO of <a href="https://brainstorm-cell.com/" rel="nofollow">BrainStorm Cell Therapeutics</a>, NurOwn&#8217;s developer, said in a <a href="https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-provides-update-on-fda-advisory-committee-meeting-to-review-nurown-for-the-treatment-of-als-301941169.html">company press release</a>, adding, &#8220;The people of BrainStorm will do everything in our power to fulfill the obligation we deeply feel we owe to the ALS community, and in the coming weeks we will explore all options available to us.&#8221;
[recommended-reading id=85498]
<h3>FDA found no evidence of so-called floor effect in trial</h3>
NurOwn is a cell-based therapy that involves harvesting stem cells from a patient&#8217;s bone marrow, engineering them in a laboratory so they secrete molecules that promote nerve health, and then infusing the cells back into the patient&#8217;s spine.
Following a decade of testing, BrainStorm submitted an application to the FDA last year seeking approval of NurOwn in the U.S. The agency initially <a href="https://alsnewstoday.com/news/fda-declines-considering-nurown-als/">refused to review</a> the application, saying there was not enough evidence to support an approval.
However, but BrainStorm forced a new review and an advisory committee meeting using the <a href="https://alsnewstoday.com/news/als-therapy-maker-brainstorm-secures-adcom-over-fda-objection/">FDA’s “file over protest” procedure</a>.
BrainStorm&#8217;s application includes data from several clinical trials, including a large <a href="https://clinicaltrials.gov/ct2/show/NCT03280056">Phase 3 study (NCT03280056)</a> that tested NurOwn against a placebo in 189 people with rapidly-progressing ALS.
The study aimed to show that NurOwn could slow the progression of the disease, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), a standardized measure that assesses a person&#8217;s ability to perform activities of daily living. But final results showed <a href="https://alsnewstoday.com/news/nurown-fails-to-slow-disease-progression-in-als-patients-top-line-data-show/">no difference in progression</a> between patients given NurOwn or a placebo.
The company argued that this might be due to a so-called <a href="https://alsnewstoday.com/news/mda-2023-issues-als-scale-noted-nurown-trial-failure-analysis/">floor effect</a> —  where some patients had ALSFRS-R scores so low that they couldn&#8217;t meaningfully get lower.
In post hoc analyses done once the study was over, the company analyzed only subsets of patients expected not to have a floor effect. Those results <a href="https://alsnewstoday.com/news/nurown-benefits-patients-less-severe-als-analyses-show/">generally suggested</a> slower disease progression with NurOwn compared with a placebo.
In briefing documents put out before the committee meeting, the FDA said it <a href="https://alsnewstoday.com/news/fda-questions-nurown-efficacy-quality-ahead-advisory-panel/">did not find evidence</a> of a floor effect in the patients that BrainStorm had flagged. The agency also cautioned that post hoc analyses are heavily prone to false-positive results, and, overall, reiterated its stance that there are not enough data to support an approval of NurOwn.
[quote=&#8221;center&#8221;]The committee&#8217;s vote was a sad outcome for the ALS community, who have too few options to help manage this merciless and deadly disease.[/quote]
The advisory committee has now strongly voted that the available data are not enough to demonstrate that NurOwn is effective in ALS — a decision that further supports a potential rejection by the FDA.
&#8220;The committee&#8217;s vote was a sad outcome for the ALS community, who have too few options to help manage this merciless and deadly disease,&#8221; said Stacy Lindborg, PhD, co-CEO of BrainStorm.
&#8220;We firmly believe that the totality of data presented for NurOwn today provide a compelling case for approval, with clinical evidence in those with less advanced disease supported by strong and consistent biomarker data that are predictive of clinical response,&#8221; Lindborg said.
Lindborg suggested that too little time was given during the meeting for BrainStorm to answer all of the committee&#8217;s questions.
&#8220;We truly did our best to make the NurOwn data clear to the FDA advisory committee. Unfortunately, had more time and opportunity been allowed, many remaining questions posed by advisory committee members could have been sufficiently addressed,&#8221; Lindborg said.

FDA advisory committee votes against NurOwn approval for ALS

Note: This story was updated Aug. 22, 2023, to correct there are four ALS approved therapies widely available in the U.S.
Diarrhea associated with a common <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) treatment could be a substantial barrier to complying with the medication, according to surveys by <a href="https://napopharma.com/">Napo Pharmaceuticals</a>.
While the name of the ALS therapy was not disclosed — the survey referred only to the “ALS drug” — only four therapies are now widely available in the U.S. These include riluzole (sold as <a class="c-link" tabindex="-1" href="https://alsnewstoday.com/als-treatment/rilutek-riluzole/" target="_blank" rel="noopener noreferrer" data-stringify-link="https://alsnewstoday.com/als-treatment/rilutek-riluzole/" data-sk="tooltip_parent" data-remove-tab-index="true">Rilutek</a> and generics <a class="c-link" tabindex="-1" href="https://alsnewstoday.com/tiglutik-riluzole-oral-suspension/" target="_blank" rel="noopener noreferrer" data-stringify-link="https://alsnewstoday.com/tiglutik-riluzole-oral-suspension/" data-sk="tooltip_parent" data-remove-tab-index="true">Tiglutik</a> and <a class="c-link" tabindex="-1" href="https://alsnewstoday.com/exservan-riluzole-oral-film/" target="_blank" rel="noopener noreferrer" data-stringify-link="https://alsnewstoday.com/exservan-riluzole-oral-film/" data-sk="tooltip_parent" data-remove-tab-index="true">Exservan</a>) and edaravone (sold as <a class="c-link" tabindex="-1" href="https://alsnewstoday.com/radicava-edaravone-for-als/" target="_blank" rel="noopener noreferrer" data-stringify-link="https://alsnewstoday.com/radicava-edaravone-for-als/" data-sk="tooltip_parent" data-remove-tab-index="true">Radicava and Radicava ORS</a>), as well as the more recently approved <a class="c-link" tabindex="-1" href="https://alsnewstoday.com/amx0035/" target="_blank" rel="noopener noreferrer" data-stringify-link="https://alsnewstoday.com/amx0035/" data-sk="tooltip_parent" data-remove-tab-index="true">Relyvrio</a> (sodium phenylbutyrate and taurursodiol) and <a class="c-link" tabindex="-1" href="https://alsnewstoday.com/ionis-sod1-rx-biib067/" target="_blank" rel="noopener noreferrer" data-stringify-link="https://alsnewstoday.com/ionis-sod1-rx-biib067/" data-sk="tooltip_parent" data-remove-tab-index="true">Qalsody</a> (tofersen).
Doctors, patients, and caregivers who were surveyed reported diarrhea as a substantial burden with the medication and it influenced patients&#8217; quality of life, leading to discontinuing treatment in many cases.
&#8220;The results of both surveys indicate that chronic diarrhea may be a substantial compliance issue of patients receiving the ALS drug, and that the severity of the diarrhea — and its impact on patient quality of life, dignity, and the ability of patients to remain on the drug — may be higher than previously understood,&#8221; Lisa Conte, president and CEO of Napo&#8217;s parent company Jaguar Health, said in a <a href="https://www.biospace.com/article/releases/napo-pharmaceuticals-surveys-of-neurologists-patients-and-caregivers-regarding-amyotrophic-lateral-sclerosis-als-treatment-indicate-real-world-burden-of-diarrhea-and-potential-treatment-interruption/">company press release</a>.
Napo markets a treatment called crofelemer under the brand name <a href="https://mytesi.com/">Mytesi</a> for diarrhea in adults with HIV/AIDS who are on anti-retroviral therapy. The company is investigating crofelemer for other indications, including ALS.
[recommended-reading id=75076]
<h3>Impact of diarrhea</h3>
Napo conducted two survey studies, one of 15 neurologists who treat ALS patients in the U.S. and another involving 15 patients or caregivers, to learn more about the burden of diarrhea with the disease.
Most neurologists (87%) said the severity of diarrhea linked to the ALS medication was moderate or severe for their patients and 13% said their patients had been hospitalized or required medical interventions for diarrhea while taking it.
This aligned with the patient and caregiver survey, where 93% reported diarrhea severity as moderate or higher and 27% said it was severe. The need for hospitalization or medical intervention was reported by 40%.
About two-thirds of patients and caregivers reported experiencing diarrhea throughout their time on the ALS medication, with 20% saying the symptoms increased over time.
These side effects were associated with significant quality of life impacts, with 79% of doctors saying diarrhea had a moderate to severe effect on their patients&#8217; quality of life and 93% of patients and caregivers reporting moderate or greater life quality impacts.
More than half of physicians said they&#8217;d stopped prescribing the medication due to diarrhea and 40% said their patients had skipped doses. Nearly half of respondents in the patient/caregiver survey said the treatment was stopped because of diarrhea. Less than half of the patients took medications for managing it.
&#8220;The data from the Napo-sponsored survey of individuals who are either ALS patients or caregivers of an ALS patient underscores the importance of real-world patient reported outcomes (PRO) data and the importance of managing side effects for critical diseases such as ALS,&#8221; Conte said.
<h3>Potential of crofelemer</h3>
Napo believes crofelemer could help ALS patients. The therapy is a plant-based medication purified from red bark sap — known as &#8220;dragon&#8217;s blood&#8221; — from the Croton lechleri tree in the Amazon rainforest.
The company notes it has established a sustainable harvesting program under fair trade practices that ensure high quality, ecological integrity, and support for indigenous communities in the rainforest.
The molecule inhibits channels in the gastrointestinal tract that mediate the movement of chloride into and out of cells. It works to help normalize the electrolyte and fluid balance in the gut to prevent diarrhea.
&#8220;We believe it is important to evaluate the potential of crofelemer&#8217;s novel mechanism of action to improve the quality of life of patients treated with the ALS drug and help prevent discontinuations and dose reductions of their disease modifying medications due to diarrhea,&#8221; Conte said.
While there&#8217;s no clinical trial involving ALS patients, a Phase 3 trial called <a href="https://clinicaltrials.gov/study/NCT04538625?term=crofelemer&amp;page=2&amp;rank=12">OnTarget (NCT04538625)</a> is evaluating crofelemer as a preventive treatment in adult cancer patients.

Diarrhea a barrier to using common ALS medication: Surveys

<a href="https://coyatherapeutics.com/">Coya Therapeutics</a> is planning to file a request with the U.S. Food and Drug Administration (FDA) to continue testing its investigational therapy COYA 302 for the treatment of <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) in a Phase 2 clinical trial.
The company is preparing a meeting with the regulatory agency to discuss its development plans and ensure they align with FDA expectations and requirements before submitting the investigational new drug (IND) application.
The pre-IND meeting will take place this fall, and the company is hoping to have the application cleared early next year, with plans to initiate the clinical trial soon thereafter.
“We are preparing for a pre-IND meeting with the FDA in the fall of 2023,” Howard Berman, PhD, CEO of Coya, said in a <a href="https://www.businesswire.com/news/home/20230808949580/en/Coya-Therapeutics-Inc.-Provides-Business-Update-and-Reports-Q2-2023-Unaudited-Financial-Results">company press release</a>. “We hope to have our IND application for a phase 2 trial accepted by the FDA early next year and are optimistic the trial can begin soon thereafter.”
ALS is marked by the <a href="https://alsnewstoday.com/symptoms-of-als/">progressive damage and death of motor neurons</a>, the nerve cells that control voluntary movements. With the loss of these neurons, the brain becomes less and less able to control muscle movement.
COYA 302 is a combination of the immune signaling molecule interleukin-2 (IL-2) and a fusion protein named CTLA4-Ig or abatacept. It is administered via a subcutaneous (under-the-skin) injection.
[recommended-reading id=85814]
<h3>Reducing inflammation, decreasing activity of damaging immune cells</h3>
The low-dose IL-2 in the combination is intended to reduce inflammation by increasing the activity of anti-inflammatory immune cells called regulatory T-cells (Tregs). CTLA4-Ig, in turn, is designed to decrease the activity of immune cells that promote inflammation and damage in ALS.
The therapy was tested in a small proof-of-concept trial involving four people with ALS. Participants were treated with COYA 302 for 48 weeks and were followed for eight more weeks after stopping the medication.
Results showed that COYA 302 resulted in a <a href="https://alsnewstoday.com/news/mda-2023-coya-302-therapy-slows-als-progression-early-trial/">considerable slowing of disease progression</a>. While participants were losing about 1.1 points per month in the ALS Functional Rating Scale (ALSFRS-R) — a measure of functional ability — before starting on COYA 302, they lost an average of 1.5 points in the whole trial duration.
However, once patients stopped the treatment, disease progression rates went back to those observed before treatment.
Analysis of immune cell function showed similar findings, with Treg activity increasing during treatment as expected, but decreasing once patients stopped treatment. Other markers of inflammation and oxidative stress, a type of cell damage associated with inflammation, also decreased with COYA 302.
The therapy was generally well tolerated, with no serious side effects described. The most common side effects were injection site reactions, which were mostly mild in severity.
Coya now expects to release data from biomarker analyses, and also publish full results from the trial in a peer-reviewed journal, before year&#8217;s end.

Coya to meet with FDA about a Phase 2 trial of COYA 302 for ALS

It&#8217;s been nearly three years since the HEALEY platform clinical trial started and, so far, two promising experimental treatments for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) have been identified.
Both potential medications — <a href="https://alsnewstoday.com/cnm-au8/">CNM-Au8</a> and <a href="https://alsnewstoday.com/pridopidine-experimental-treatment-als/">pridopidine</a> — are headed toward Phase 3 clinical testing, while testing has been ruled out for two others.
&#8220;Since we launched in the summer of 2020, we&#8217;ve had two no-go decisions and moved two drugs to Phase 3 testing,&#8221; said Sabrina Paganoni, MD, PhD, a physician-scientist at Massachusetts General Hospital (MGH) and the trial&#8217;s co-lead investigator.
Paganoni discussed the findings at this week&#8217;s American Academy of Neurology (AAN) 2023 Annual Meeting in the oral presentation, &#8220;Results from the First Four Regimens of the HEALEY ALS Platform Trial.&#8221;
The <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1">HEALEY platform trial (NCT04297683)</a>, led by the Sean M. Healey &amp; AMG Center for ALS at MGH, intends to test multiple potential <a href="https://alsnewstoday.com/als-treatment/">ALS therapies</a> at once, an approach that may help reduce the cost and time associated with drug development.
&#8220;A platform trial is a novel approach to trial design. The goal of platform trials is to develop new drugs faster and more efficiently, and we do so by using a common infrastructure or platform,&#8221; Paganoni said, noting the platform approach hasn&#8217;t been tried before in ALS, but has led to &#8220;savings across the board,&#8221; including in time, money, and patient resources in cancer studies.
&#8220;This is the perfect time for a platform trial in ALS, because like never before we have a very robust and growing drug pipeline and companies are looking for ways to develop their drugs most efficiently,&#8221; Paganoni said.
HEALEY encountered obstacles soon after its launch that arose from the COVID-19 pandemic. &#8220;As you can imagine, this was challenging because this was at the very beginning of the pandemic, but COVID did not stop ALS trials,&#8221; Paganoni said. &#8220;In fact, we continued to grow and experienced great enrollment rates.&#8221;
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<h3>Participation in HEALEY trial</h3>
Enrollment has been completed for five potential therapies, including zilucoplan, verdiperstat, CNM-Au8, pridopidine, and <a href="https://seelostherapeutics.com/sls-005-trehalose/">SLS-005</a>. The sixth trial arm testing ABBV-CLS-7262 started <a href="https://www.massgeneral.org/news/press-release/the-healey-als-platform-trial-enrolls-first-participants-for-the-investigational-product-abbv-cls-72-from-calico-life-sciences">enrolling last month</a> and the DNL343 arm is expected to begin <a href="https://alsnewstoday.com/news/aan-2023-dnl343-safe-appears-work-intended-phase-1-trial/">later this year</a>.
Patients enrolling in the trial don&#8217;t choose which treatment arm they&#8217;ll enter. They&#8217;re randomly assigned to one of the arms that&#8217;s enrolling at the time they join.
&#8220;When we started the trial, people asked us: &#8216;Will patients want to enroll in a new type of trial, a platform trial, where they cannot choose the drug they are assigned to?&#8217; And the answer to that is a resounding yes. Patients are eager to learn about and participate in innovative research,&#8221; Paganoni said, adding trial sites have also been eager to join. More than 70 clinics across the U.S. are participating in HEALEY.
Paganoni&#8217;s presentation covered data from the first four treatment arms, testing the experimental therapies zilucoplan, verdiperstat, CNM-Au8, and pridopidine, respectively.
In each treatment arm, most participants were given the investigational drug while a few were given a placebo. Because each treatment arm uses the same eligibility criteria, data from patients given each treatment can be compared with data from those given a placebo across all arms of the study.
The main goal of each treatment arm is to compare the effect on survival and disease progression, as measured by the ALS Functional Rating Scale Revised (ALSFRS-R), after six months.
Researchers also regularly carried out interim analyses to test for futility — in other words, statistical tests based on available data to check if there was a reasonable likelihood the therapy may provide a benefit for patients.
<h3>Disappointment with zilucoplan, verdiperstat</h3>
The first treatment arm for zilucoplan ended early after futility analyses showed it was <a href="https://alsnewstoday.com/news/ucb-stops-zilucoplan-arm-early-healey-trial-als-lack-of-efficacy/">unlikely to be beneficial</a>.
&#8220;While this was disappointing, it actually in a way met the goals of the trial, which is really to screen out drugs rapidly. So we were able to end this regimen early, saving months of operational activities,&#8221; Paganoni said.
Data from the second arm showed <a href="https://alsnewstoday.com/news/als-therapy-verdiperstat-fails-healey-trial-efficacy-goals/">verdiperstat failed to significantly slow ALS progression</a> and that arm has also been discontinued.
Findings from the third and fourth trial arms have been more promising, however.
[recommended-reading id=83515]
<h3>CNM0Au8, pridopidine move toward Phase 3 testing</h3>
Data from the third arm suggested CNM-Au8, at a daily dosage of 30 mg, <a href="https://alsnewstoday.com/news/cnm-au8-found-lower-risk-death-als-healey-platform-trial/">significantly reduced the risk of death</a> and the combined risk of death or permanent assisted ventilation by more than 90%. Recent analyses also suggested CNM-Au8 <a href="https://alsnewstoday.com/news/cnm-au8-delayed-clinical-worsening-als-patients-healey-trial/">delayed clinical worsening</a>. The treatment is designed to boost energy production in the nervous system.
Long-term data from a separate Phase 2 trial, <a href="https://clinicaltrials.gov/ct2/show/NCT04098406">RESCUE-ALS (NCT04098406)</a> and its <a href="https://clinicaltrials.gov/ct2/show/NCT05299658">open-label extension (NCT05299658)</a>, indicated early CNM-Au8 treatment may <a href="https://alsnewstoday.com/news/slower-progression-experimental-als-treatment-cnm-au8/">slow disease progression</a> and <a href="https://alsnewstoday.com/news/early-cnm-au8-treatment-als-continues-show-survival-benefits/">reduce the risk of death</a>. Findings from early clinical trials of CNM-Au8 in <a href="https://multiplesclerosisnewstoday.com/multiple-sclerosis-overview/">multiple sclerosis</a> (MS) have <a href="https://multiplesclerosisnewstoday.com/news-posts/2023/03/01/actrims-2023-cnm-au8-bound-phase-3-testing-after-positive-data/">also been promising</a>.
&#8220;With this growing body of evidence, we are increasingly confident that CNM-Au8 has an effect across neurodegenerative diseases, such as ALS and MS, providing a potential treatment option with a novel and complementary mechanism of action for the patient community,&#8221; Rob Etherington, president and CEO of CNM-Au8&#8217;s developer <a href="https://clene.com/">Clene Nanomedicine</a>, said in a <a href="https://invest.clene.com/news-releases/news-release-details/als-and-ms-clinical-data-clenes-cnm-au8r-featured-multiple">company press release</a>.
In the fourth arm, pridopidine failed to show an effect on ALSFRS-R scores or survival outcomes in the overall group, but <a href="https://alsnewstoday.com/news/pridopidine-shows-some-potential-in-healey-trial-but-misses-main-goal/">promising trends</a> were seen for patients with early, rapidly progressing disease.
Pridopidine also significantly improved objective measures of speech function in a pre-specified analysis.
&#8220;This was of great interest to us because of the mechanism of action of pridopidine,&#8221; Paganoni said, noting the therapy is thought to act on a type of protein involved in regulating mouth and throat functions.
Pridopidine&#8217;s developer <a href="https://www.prilenia.com/">Prilenia Therapeutics</a> recently announced positive data from a Phase 3 study testing pridopidine in Huntington’s disease (HD).
&#8220;Pridopidine showed encouraging results for the potential treatment of ALS that deserve further exploration,&#8221; Merit Cudkowicz, MD, the HEALEY trial lead investigator, said in a <a href="https://www.businesswire.com/news/home/20230424006021/en/Prilenia-Shares-Preliminary-Topline-Results-from-Phase-3-PROOF-HD-Clinical-Trial-in-Huntington">press release from Prilenia</a>.
&#8220;The impact of pridopidine on rater-independent speech measures was especially notable &#8230; Speech is a highly clinically relevant endpoint in ALS studies and more than 80 percent of ALS patients become speech impaired, which significantly impacts their quality of life,&#8221; said Cudkowicz, the director of the Healey &amp; AMG Center and chief of the department of neurology at MGH.
The CNM-Au8 and pridopidine arms are still collecting more long-term data. Clene is working to launch a Phase 3 study of CNM-Au8 and Prilenia is exploring Phase 3 ALS testing of pridopidine.
&#8220;Clene now awaits important new biomarker data from both the double-blind and open label periods of the HEALEY ALS Platform Trial &#8230; These data will help determine our regulatory filing strategy,&#8221; Etherington said. &#8220;In parallel, Clene plans to meet with the FDA in an end of Phase 2 meeting during the third quarter of 2023 to discuss the regulatory path forward for CNM-Au8 in ALS.&#8221;

AAN 2023: ALS treatments ID’d in HEALEY head toward Phase 3 tests

Note: This story was updated March 10, 2023, to correct a secondary headline to note the therapy was tracked for less than a year. The story also clarifies the timing of results from a Phase 3 clinical trial and that edaravone is believed to reduce oxidative stress.
Radicava ORS, an oral formulation of <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava</a> (edaravone), was well tolerated among people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) over nearly a year of treatment in a clinical trial.
Findings from the trial had <a href="https://alsnewstoday.com/news/edaravone-oral-form-shows-good-tolerability-over-one-year-use/">been announced </a><a href="https://alsnewstoday.com/news/edaravone-oral-form-shows-good-tolerability-over-one-year-use/">previously</a> by the therapy&#8217;s developer <a href="https://www.mt-pharma-america.com/">Mitsubishi Tanabe Pharma America</a> (MTPA), and 24-week data from the trial helped form the basis of the U.S. Food and Drug Administration (FDA)&#8217;s <a href="https://alsnewstoday.com/news/fda-approves-radicava-ors-oral-suspension-edaravone-als/">approval of Radicava ORS last year</a>.
The results have now undergone peer review and were detailed in the study, &#8220;<a href="https://onlinelibrary.wiley.com/doi/full/10.1002/mus.27768">Oral edaravone demonstrated a favorable safety profile in patients with amyotrophic lateral sclerosis after 48 weeks of treatment</a>,&#8221; published in <a href="https://onlinelibrary.wiley.com/journal/10974598">Muscle &amp; Nerve</a>. The work was funded by MTPA.
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&#8220;We&#8217;re encouraged by the data that we continue to collect from the global Phase 3 trial of Radicava ORS, demonstrating a favorable safety profile after 48 weeks of treatment,&#8221; Gustavo Suarez Zambrano, MD, vice resident of medical affairs at MTPA, said in a <a href="https://www.prnewswire.com/news-releases/mitsubishi-tanabe-pharma-america-announces-48-week-results-from-global-open-label-phase-3-trial-of-radicava-ors-edaravone-in-als-301756250.html">press release</a>. &#8220;These data build upon the study&#8217;s 24-week findings that supported the FDA approval of Radicava ORS.&#8221;
While the mechanism of action of edaravone, the active agent in Radicava and Radicava ORS, is unknown, it is believed to reduce oxidative stress — a type of cell damage that’s thought to play a critical role in driving <a href="https://alsnewstoday.com/causes-of-als/">nerve cell death in ALS</a>. The original therapy was designed to be delivered intravenously (via infusion into the bloodstream), and results from clinical trials showed that it <a href="https://alsnewstoday.com/news-posts/2020/03/30/radicava-effective-slowing-als-progression-across-1-year-use-patients-trial-data/">slowed functional decline</a> in people with early ALS.
Radicava ORS was designed to deliver the same active ingredient, but in an oral form that would be more convenient for patients. Pharmacological studies have demonstrated that a 105 mg dose of oral Radicava ORS delivers the same amount of edaravone as the approved 60 mg dose of intravenous Radicava. MTPA conducted a <a href="https://clinicaltrials.gov/ct2/show/NCT04165824">Phase 3 clinical trial (NCT04165824)</a> aiming to assess the safety of the oral formulation.
The study enrolled 185 adults <a href="https://alsnewstoday.com/als-diagnosis/">diagnosed with ALS</a> at sites in the U.S., Canada, Japan, Germany, France, and Italy. The average participant age was around 60 years, and the average disease duration was about 1.5 years. About 80% of patients had <a href="https://alsnewstoday.com/forms-of-als/">limb-onset disease</a>, while the rest had bulbar-onset.
<h3>Four-week cycles</h3>
All of the patients were treated with Radicava ORS, administered in four-week treatment cycles similar to how the intravenous formulation is given: two weeks of taking the therapy, and then two weeks off in the first cycle, and then 10 days of treatment in the first two weeks, followed by two weeks off in subsequent cycles.
Most of the patients (87%) also were being treated with riluzole (sold as <a href="https://alsnewstoday.com/als-treatment/rilutek-riluzole/">Rilutek</a> and other formulations), and nearly one in five (18.4%) had been on intravenous Radicava previously.
The study lasted 48 weeks (almost a year). About 25% of the participants did not complete the full 48 weeks of treatment, mainly due to experiencing safety issues, death due to ALS, or due to the patient&#8217;s choice. The researchers said this rate is &#8220;comparable with or slightly lower than other recent clinical trials in ALS.&#8221;
Safety-related events were reported in nearly every participant over the course of the study, though many of these events were judged to be a result of ALS disease progression and not considered related to treatment with Radicava ORS.
By 48 weeks, about one quarter (24.9%) of the participants had experienced safety-related events that were judged by study investigators to be likely side effects of the oral therapy. The most common side effects were fatigue, dizziness, headache, and constipation. No treatment-related side effects were judged to be serious.
<h3>Findings consistent with IV Radicava</h3>
These findings were generally consistent with the known safety profile of intravenous Radicava, the researchers said.
&#8220;The 48-week results from this trial suggest that RADICAVA ORS was well tolerated, and support its long-term use as a treatment for ALS. Our hope is for these data to provide additional information to physicians who are considering this oral treatment option for their patients,&#8221; said Gary Pattee, MD, a neurologist and ALS specialist who works in Nebraska.
Over the course of the study, the average forced vital capacity (FVC) — a standardized measure of lung function based on how much someone can forcibly exhale — decreased by an average of 25.1%. Again, the researchers said this is consistent with prior trial results for intravenous Radicava, where the average decline in FVC was 15.6% for those on therapy, compared to 20.4% for patients given a placebo.
&#8220;This trial provides safety data to support the use of oral [Radicava ORS], which expands on existing evidence supporting the use of FDA-approved [intravenous Radicava] and the recently approved oral suspension formulation,&#8221; the scientists concluded.

Tag: ALS treatment