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  • Writer's pictureAdults Living Rare

Great news for Rett syndrome and other similar rare diseases on the autism spectrum

After receiving the disappointing news that GW Pharmaceuticals has made the difficult decision to discontinue their cannabidiol study in mid November, today, the Rett syndrome community has a reason to celebrate.

The results of a US-based Phase 2 clinical trial evaluating the safety and efficacy of Anavex Life Sciences‘ investigational therapy ANAVEX®2-73 (blarcamesine) in Rett syndrome has been published, effectively establishing a human proof-of-concept that has resulted in a widespread celebration from within the rare disease advocacy community.

Rett syndrome is a rare neurodevelopmental disorder that almost exclusively affects girls. Estimated to occur in one of every 10,000 to 23,000 female births, the condition affects brain function and results in cognitive, emotional, sensory, motor, and autonomic problems. Classified as an autism spectrum disorder, Rett syndrome presents similarly to other rare autism spectrum conditions like Batten disease, Angelman syndrome, Fragile X disorders, and more.

The collective mindset of the Rare Advocacy Movement establishes “a win for one is a win for us all.” This sentiment couldn’t be more true in the case of today’s release of the results of the ANAVEX®2-73 (NCT03758924) trial in Rett syndrome. Here is why:

1. While the trial was done in Rett syndrome, this precision medicine therapeutic shows significant promise for a large group of rare autism spectrum disorders. According to Christopher U. Missling, PhD, President and CEO of Anavex, in a video response to the press release the mechanism of action of ANAVEX®2-73 has a strong possibility to work in other similar autism spectrum disorders, evidenced by robust preclinical animal models in other related indications. ANAVEX®2-73 is an oral small molecule, which can be taken once daily as a convenient liquid formulation with a broad pipeline target of neurodevelopmental autism spectrum disorders with significant unmet medical need. Designed to activate the protein sigma-1 receptor (S1R), which is involved in proper protein folding, ANAVEX®2-73 reduces the toxic accumulation of misfolded proteins in nerve cells, effectively reducing inflammation and cellular stressors in the brain (see figure below).​

While the study’s main goals were to evaluate the treatment’s safety — as assessed by reported adverse events — and to assess how the medicine is processed within the body, efficacy was also analyzed using two measurements: the caregiver-reported Rett Syndrome Behaviour Questionnaire and the Clinical Global Impressions Scale. Results show that treatment with ANAVEX®2-73 has led to improvements in both assessments. Additionally, plasma levels of glutamate, a biomarker of disease progression, were decreased in the active drug arm within the seven week time frame.

“The really exciting part is that there is extremely promising pre-clinical data that shows the drug has a strong possibility to work in other similar autism spectrum disorders, like Batten disease, Fragile X, Angelman syndrome and infantile spasms.” Dr. Missling stated in an exclusive interview.

This drug has demonstrated a robust safety and efficacy precision medicine profile in global aging central nervous system diseases (like Alzheimer’s and Parkinson’s) and in rare disease communities with high unmet needs. 2. The study exclusively enrolled adult women 18 to 45 years of age with a progressive neurodegenerative rare disease. The ANAVEX®2-73 (NCT03758924) trial enrolled 31 participants across the U.S., all women with Rett Syndrome ages 18-45. Aside from the amazing news that the drug has shown significant improvement in key domains with no serious adverse events, the fact that all of the trial participants were adult women 18 to 45 years of age is extremely significant. Traditionally, rare disease advocacy efforts have primarily focused on rare pediatric conditions. This historical dynamic resulted in the overall neglect of 71% of the rare disease community, rare disease adults. As identified in RAM’s Adults Living Rare initiative, rare disease people feel abandoned once they turn 18 years of age and no longer qualify as a pediatric patient. “When I was younger at a children’s hospital, I was a miracle to them. But after I became an adult it was very hard to find doctors to work with me. I feel abandoned as an adult,” answered an Adult Living Rare after being asked, “what would you most like to see for adult rare disease patients?” Dr. Missling explains during his exclusive interview that, “too many biopharmaceutical companies have been afraid to approach allocating resources to the adult population because there is this misconception that too much time has passed and there is nothing that they can do.” As a result Dr. Missling and his colleagues at Anavex entered into a collaborative relationship with community-based advocates from the Rett syndrome community to design a trial for a neglected adult community. Together, Dr. Missling’s team worked with skilled community-based advocates to design a trial for adult girls with Rett syndrome that did not require travel. Even the necessary blood work required to meet the trial’s protocols were taken at the patient’s home. As a result of incorporating unadulterated community insights into the trial’s design and protocols, not even the devastating COVID-19 pandemic disrupted the trial. Because of Dr. Missling’s human-focused approach to clinical trial design and his refusal to shy away from working with neglected adult rare disease populations, his team was able to collect efficacy data that may bring a quality of life improving treatment to a widespread variety of rare disease autism spectrum disorders. 3. The study was designed with the removal of the misinformed corporate advocacy lens from the drug development process. It has been over ten years since the biopharmaceutical industry shifted its marketing efforts from directly to healthcare professionals to their true clients, the patient community. During this shift a variety of consulting agencies developed in partnership with industry to develop “patient-centric” protocols and strategies, effectively excluding community-based advocates from participating as equal stakeholders in the drug development continuum.

As a direct result of not working directly with community-based advocacy experts, a majority of biopharmaceutical manufacturers have been incorporating misinformed insights, obtained through alternative advocacy partnerships that have been filtering community insights through the corporate advocacy lens.

Consequently, clinical trial design and protocol development for promising treatment options have been unnecessarily burdensome to participants; according to a Tufts CSDD survey, about 90% of U.S. trials fail to hit recruitment targets on time. And the rare disease community grows increasingly emotionally exhausted every time a drug developer makes the difficult business decision to discontinue a promising study.

As a result, the Rare Advocacy Movement is amplifying Dr. Missling’s approach to “patient-centricity” as novel, in the sense that he partnered with comprehensive rare disease advocacy experts early. Through the establishment of collaborative relationships with community-based advocates, Missling and his team incorporated unadulterated community-based insights into the design of the trial, effectively removing burden to participation, establishing accurate real world endpoints, and even exceeding original recruitment goals.

It is not enough to simply claim understanding of the value of community-based insights and early collaborations. You have to actually do it and the team at Anavex did just that.

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