Treatment with RT001 Results in Statistically Significant Improvements in Overall Survival and Progression Free Survival for INAD Patients as Compared to Control

Benefits Supported by Totality of Evidence Across Modified Ashworth Spasticity Scale and Other Efficacy Measurements with RT001 Treatment as Compared to Control, Though Did Not Reach Statistical Significance

Company to Meet with U.S. Food and Drug Administration to Discuss Regulatory Pathway in INAD, for which RT001 Has Been Granted Rare Pediatric Disease Designation

LOS ALTOS, CA, USA I October 6, 2021 I Retrotope, a clinical-stage biopharmaceutical company focused on the development of novel, first-in-class therapies for degenerative diseases, today reported data from its Phase 2/3 clinical trial of RT001 in patients with infantile neuroaxonal dystrophy (INAD) and its concurrent natural history study of disease onset and progression in INAD patients. Results demonstrated statistically significant improvements in overall survival and progression free survival for patients treated with RT001 as compared to control. These survival endpoints included a combination of efficacy and safety measures. Additionally, clinical improvements were observed in patients receiving RT001 as measured by the Modified Ashworth Spasticity Scale, the study’s primary efficacy endpoint, and other measurements of efficacy as compared to patients in the natural history study. These single efficacy outcomes did not reach statistical significance likely due to the small study size.

“INAD is an ultra-rare, relentlessly progressive and fatal disease that currently has no approved treatments. This trial compared a group of children with INAD treated with RT001 with a natural history cohort, and the results indicate that RT001 slows progression and prolongs survival compared to no treatment,” said Alex Fay, M.D., Ph.D., assistant professor of neurology, University of California, San Francisco and one of the study’s principal investigators. “The findings are striking and suggest that RT001 has the potential to deliver a meaningful impact on neurological function and survival of children with INAD.”

The treatment study of RT001 included 19 INAD patients and the concurrent natural history study included 36 INAD patients as the control arm.  There were no significant differences in the baseline characteristics between the two patient populations.  Patients in the treatment study received RT001 for a minimum period of one year with a 30-day treatment free follow up period. Patients treated with RT001 showed an improvement of 6.42 rank points on the Modified Ashworth Spasticity Scale as compared to control patients (p = 0.14). Similar treatment benefits were seen favoring RT001-treated patients as compared to controls across all five of the analyzed efficacy outcome scales, ranging from improvements of 4.5 to 7.3 rank points.

Study investigators evaluated progression free survival (absence of pneumonia or death event) as a pre-specified secondary endpoint, with results demonstrating a statistically significant 82.5% reduction in morbidity risk for RT001-treated patients as compared to controls (hazard ratio = 0.175, p = 0.021). Additionally, the pre-specified exploratory endpoint of survival demonstrated a statistically significant mortality risk decrease of 88.8% for treated patients as compared to control patients (hazard ratio = 0.112, p = 0.014). Overall, the number of confirmed deaths during the study were dramatically lower in RT001-treated patients (2/19, 11%) than in the control patients (11/36, 31%). Similarly, the number of patients with progression (confirmed pneumonia or death) during the study, were far lower in treated patients (4/19, 21%) than in control patients (12/36, 33%).

INAD is an ultra-rare, progressive, fatal, infant genetic neurological disorder, making it ethically challenging to enroll infants and toddlers battling this disease into a placebo-controlled trial.  Due to this limitation, Retrotope established a development strategy for RT001 in INAD comprised of an open-label treatment study to assess the clinical impact of RT001 in INAD patients and a corresponding open-label natural history trial designed to establish historical control baselines for disease progression and severity. The company previously submitted a statistical analysis plan (SAP) to the U.S. Food and Drug Administration (FDA) for these studies that involved comparisons between RT001-treated patients in the treatment study and untreated control patients in the natural history study.

“The INAD patient community is in desperate need of therapeutics that can alter the course of this fatal disease, which often involves devastating cases of pneumonia as a precursor to death. The data reported by Retrotope are currently among the most compelling study results that we have seen with regard to making a difference in the lives of INAD patients and their families,” said Leena Panwala, co-founder and executive director of the INADcure Foundation. “Even though we know their drug won’t cure INAD, it showed evidence of slowing progression in some areas and reducing some complications of the disease. We look forward to following and supporting the company’s continued efforts to bring this treatment to the INAD community until a much needed cure is available.”

“INAD is caused by an inborn genetic defect that leads to neuronal cell death due to the failure to clear the toxic by-products that result from lipid peroxidation.  As such, there is compelling mechanistic rational supporting the potential of RT001 to impact the progression of INAD based on the compound’s demonstrated ability to down-regulate lipid peroxidation,” said Darius J. Adams, M.D., medical director, Jacobs Levy Genomic Medicine and Research Program, division chief, Goryeb Pediatric Genetics and Metabolism, a leading clinical and biochemical geneticist and one of the study’s principal investigators. “These promising results, collected from a well-established, rare disease study design comparing a treatment group with a natural history control, offer encouraging evidence that this approach can offer therapeutic benefit to patients battling INAD.”  

Retrotope intends to submit a meeting request with the FDA to discuss these study results and a path for submitting a regulatory approval application for RT001 in this ultra-rare, fatal disease. FDA has previously awarded Retrotope rare pediatric disease designation for RT001 in the treatment of INAD.

“We are very pleased by these top-line results and excited to meet with the FDA to discuss the next steps in our ongoing effort to bring RT001 to the INAD patient community.  With clear evidence of benefit on patient survival, as well as consistent improvements observed in all analyzed efficacy endpoints including those which measured vital function and activities of daily living, we believe these study results support the potential of RT001 to address a critical unmet need in this orphan disease patient population,” said Peter G. Milner, M.D., chief medical officer of Retrotope. “We would like to thank all of the patients and their families, as well as the clinical investigators, who participated in these studies and helped support the further advancement of research into this devastating disease.”

About Infantile Neuroaxonal Dystrophy (INAD)

Infantile Neuroaxonal Dystrophy is an ultra-rare, infantile genetic neurological disorder and part of a spectrum of diseases called PLA2G6-associated neurodegeneration. An inborn genetic defect in the PLA2G6 enzyme results in the inability to effectively clear the toxic by-products of lipid peroxidation (LPO), which create a “death signal” that results in rapid neuronal cell death in a developing infant’s brain. This causes irreversible loss of vital functions, including gross motor, communication skills, bulbar function, recurrent aspiration pneumonia and eventual death within a matter of years. Symptoms usually present between six and 18 months of age and there is often rapid onset of motor and intellectual regression. Later on, diminished muscle tone (hypotonia) and spasticity develop. The disease also leads to problems with vision and the eyes, the autonomic nervous system, and, in a minority of individuals, seizures. Usually, disease progression is rapid, and the disorder is invariably fatal in childhood.  There are currently no approved treatments for INAD.

About RT001

RT001 is a clinical-stage isotopically stabilized, synthetic linoleic acid (LA) discovered and developed with Retrotope’s novel platform technology.  This platform is designed to combat the oxidative stress and cellular degeneration that arises from lipid peroxidation (LPO). While all healthy human tissues undergo this physiological process of cell degeneration and repair, it is well-established that a wide range of serious degenerative diseases are precipitated when the LPO process gets out of balance. Polyunsaturated fatty acids (PUFAs), which make up cell and mitochondrial membranes throughout the body and are vital to healthy cellular function, are the target of the LPO process due to their inherent instability. Free radicals in the body exploit the instability of PUFAs to trigger chain reactions that drive LPO and the resulting degradation of these vital PUFAs.  Retrotope’s novel platform technology creates stabilized PUFAs, such as RT001, that become an integral part of all membranes and are capable of down-regulating LPO in order to protect membranes from degeneration.  RT001 has been safely administered orally on a daily basis to more than 100 patients, spanning more than 1,000 patient months. 

About Retrotope

Retrotope is a clinical-stage biopharmaceutical company focused on the development of first-in-class therapies for degenerative diseases ranging from orphan neurodegenerative indications to large market degenerative conditions.  The company leverages its proprietary drug discovery platform to create novel, disease-modifying drugs designed to combat the oxidative stress and cellular degeneration that arises from lipid peroxidation (LPO).  It does so through the creation of isotopically stabilized synthetic versions of polyunsaturated fatty acids (PUFAs) that trigger the downregulation of the LPO process.  The company’s lead development candidate, RT001, is a clinical-stage isotopically stabilized, synthetic linoleic acid (LA) that is in development for a range of orphan neurodegenerative diseases, including infantile neuroaxonal dystrophy (INAD), Friedreich’s ataxia (FA), amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and progressive supranuclear palsy (PSP).  In addition, the company is advancing its second development candidate, RT011, an isotopically stabilized, synthetic docosahexaenoic acid (DHA), toward the clinic for the treatment of dry age-related macular degeneration (AMD). For more information, please visit

SOURCE: Retrotope