Signals of Clinical Benefit Detected in Small Phase 2 Study, Suggesting Potential to Show Statistically Significant Therapeutic Benefit in Larger, Targeted Trial
Consistent Benefit vs. Placebo in Primary and Secondary Endpoints, With Greater Benefit Witnessed in More Severe Patients
LOS ALTOS, Calif., Sept. 15, 2022 (GLOBE NEWSWIRE) -- BioJiva, a clinical-stage biopharmaceutical company focused on the development of novel, first-in-class therapies for degenerative diseases, today reported data from its completed multicenter, randomized, double-blind, placebo-controlled pilot Phase 2 clinical trial evaluating RT001, the company’s lead development candidate, in patients with amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease). The trial’s prespecified primary endpoint was change from baseline in the revised ALS Functional Rating Scale (ALSFRS-R) following 24 weeks of treatment. At 24 weeks, data demonstrated that patients treated with RT001 experienced less worsening (a 3.3-point reduction from baseline) in ALSFRS-R score as compared to greater worsening (4.6-point reduction from baseline) for the placebo group. Similarly, patients treated with RT001 experienced less worsening (a 13.3-point increase from baseline) in their score on the 40-item ALS assessment questionnaire (ALSAQ40) as compared to the placebo group (a 17.2-point increase from baseline). While suggesting a signal of directional improvement with RT001 treatment, these findings did not achieve statistical significance due to the small size of the study.
This six-month randomized Phase 2 pilot study (NCT04762589), which was followed by a six-month open-label extension during which all patients received RT001, was conducted at four ALS Centers of Excellence in Europe. Investigators enrolled 43 patients with ALS who had symptom duration of less than three years. Enrolled patients had baseline ALSFRS-R scores ranging from 25 to 44, with a mean of 38.2 (+/-5.0.).
Thirty-nine of the 43 enrolled subjects completed the initial 24-week randomized phase, with 32 of those also completing the open-label extension for a full year of treatment. At Week 24, patients receiving RT001 demonstrated a worsening from baseline in ALSFRS-R score of 3.3 points (from 38.2 to 34.9), as compared to a 4.6-point worsening from baseline for the placebo group (from 38.2 to 33.6). For patients who were enrolled with more severe disease (ALSFRS-R <41 and ALSAQ40 < 20; n=33), the difference in disease progression was more pronounced with RT001 treatment (3.4-point reduction for RT001 vs. 6.3-point reduction for placebo).
Data from the study’s 24-week open-label extension portion demonstrated that a signal of clinical benefit with RT001 treatment was also evident at 12 months. As no concurrent placebo was administered after 24 weeks, 12-month comparisons were made using data from the PRO ACT Database1, a validated and predictive historical control database of ALS progression. At 12 months, RT001-treated patients demonstrated a decrease in ALSFRS-R score of 7.2 +/- 6.7 points, whereas the PRO ACT Database shows an expected worsening on the ALSFRS score at 12 months of 10.1 points. For the study’s most severe patients that completed 12 months (ALSFRS-R < 41 and ALSAQ40 < 20; n=14), the 12-month reduction in ALSFRS-R score was 5.6 +/- 9.2 points with RT001 treatment, showing an even greater slowing in disease progression.
“The promising signal of clinical benefit shown in this study with RT001 in a small group of ALS patients, combined with the continued demonstration of the well tolerated nature of the treatment, provides support for considering a larger clinical trial,” said Leonard H. van den Berg, M.D., Ph.D., professor of neurology at UMC Utrecht in the Netherlands, director of the Netherlands ALS Center, Chairman of TRICALS, an ALS clinical trial-focused European research initiative spanning 42 top research centers in 15 countries, and the principal investigator of the study. “Additionally, the study data suggest that patients with more severe ALS may have a higher likelihood of benefitting from RT001 treatment, which provides important context for considering the design and enrollment criteria for the next clinical trial.”
“We conducted this trial with the dual goals of better understanding the manner in which RT001 may potentially impact the progression of ALS and detecting a signal of therapeutic benefit for patients receiving the treatment. While a small study that was not powered to demonstrate significance, we did see trends for RT001-treated patients compared to the placebo group that suggest the potential for RT001 to offer patients meaningful clinical benefit. The learnings from this study position us to continue development of RT001 for ALS, advancing next to a larger, statistically powered study focused on the more severe patient population that appears more likely to benefit from the treatment,” said Mark G. Midei, M.D., BioJiva’s vice president for medical affairs.
About RT001
RT001 is a clinical stage isotopically stabilized, synthetic linoleic acid (LA) 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 becomes 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 breakdown of these vital PUFAs. Stabilized PUFAs, such as RT001, that become an integral part of all membranes are capable of down-regulating LPO to protect these membranes.
About ALS
Amyotrophic lateral sclerosis (ALS) is a rare, progressive neurodegenerative disease that primarily involves the nerve cells, or neurons, which are responsible for controlling voluntary muscle movements such as walking, talking and chewing. ALS and its related disorders are caused by the gradual degeneration of motor neurons, which are responsible for controlling communication between the brain and muscles responsible for voluntary movements. As these motor neurons deteriorate, communication between the brain and these muscles is impaired, leading to difficulty for patients in performing voluntary movements. As the disease progresses, voluntary muscle control becomes more difficult for patients, leading to an inability to breathe on their own and ultimately death. There is currently no cure for ALS and no effective treatment to halt, or reverse, the progression of the disease.
About BioJiva
BioJiva 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’s therapeutic pipeline consists of disease-modifying, isotopically stabilized synthetic versions of polyunsaturated fatty acids (PUFAs) that are designed to combat the oxidative stress and cellular degeneration by downregulation the lipid peroxidation (LPO) process. The company’s lead development candidate, RT001, is an isotopically stabilized, synthetic linoleic acid (LA) that is in clinical development for a range of orphan neurodegenerative diseases, including infantile neuroaxonal dystrophy (INAD), 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).
BioJiva was founded in 2022 and is advancing the development assets formerly owned by Retrotope, which it purchased through a Delaware bankruptcy proceeding under Chapter 11. BioJiva is not a progression of Retrotope and BioJiva is not the former Retrotope. Several employees, advisors, and other service providers of Retrotope have joined BioJiva as part of the new company’s efforts to develop the previously Retrotope-owned assets.
1 Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database
