The HOPEMD study was designed as a proof–of-concept open-label clinical study in 74 patients for 24 weeks, following which all patients would be randomized into a treatment arm or non-treatment control group, and followed for an additional 12 months in a continuation study. The primary objective was to assess the safety and tolerability of Cabaletta. Secondary endpoints were to determine if Cabaletta improves or prevents worsening of OPMD disease markers. As previously reported, based on the positive signals seen in the first 25 patients enrolled in
In this analysis, Cabaletta was observed to be safe and well-tolerated with no drug-related serious adverse events. Statistically significant improvement or numerical improvement versus baseline, was observed on multiple efficacy endpoints. Ten out of 12 patients (83.3%) were observed to stabilize or improve on an efficacy endpoint related to dysphagia, the Penetration Aspiration Score as measured by Video Fluoroscopy (VFS-PAS). There was a statistically significant improvement of 35.3% (p<0.0001, n=20) from baseline in the timed drinking test, also a key dysphagia measure. In addition, patients demonstrated a statistically significant improvement of 12.1% (p=0.0448, n=21) in their swallowing quality of life symptom score as measured by the SWAL-QOL questionnaire. Notably, there was a statistically significant correlation between the timed drinking test and the SWAL-QOL percent change in symptom score (p=0.0479, n=20). With respect to muscle-related efficacy endpoints, patients showed a statistically significant improvement of 13.4% (p=0.0059, n=19) in their lower extremities muscle strength versus baseline, and showed numerical improvement in other muscle strength and function tests.
"The detailed analysis of the interim results of the Phase 2 Cabaletta therapy trial for OPMD are very encouraging," stated
HOPEMD Study – Interim Safety and Efficacy Results
The interim safety and efficacy results of the Phase 2 open label study showed that, at up to 24 weeks of treatment (300mL of IV trehalose 9% solution once weekly), statistically significant improvements or numerical improvements were observed in the following endpoints, including those that BioBlast plans to incorporate into the Phase 3 protocol. All evaluable data were included in the statistical analysis of this interim report.
Safety and Tolerability -- Cabaletta was well tolerated with no drug related serious adverse events identified, a finding that is consistent with BioBlast's previous report at the
Penetration Aspiration Score as Measured by Video Fluoroscopy (VFS-PAS) -- Out of 12 patients whose scores were evaluated by VFS-PAS, a well-validated radiographic technique to determine the severity of swallowing difficulties and risk of aspiration, 10 patients (83.3%) showed stabilization (4 out of the 10) or improvement (6 out of the 10) in their VFS-PAS scores. Seven patients enrolled in
Timed Drinking Test – There was a statistically significant 35.3% improvement versus baseline (p<0.0001) in the timed drinking test (80mL cold water), a frequently used and validated clinical test of swallowing dysfunction. The improvement in the timed drinking test correlated with patient reported severity of their symptoms, further attesting to the clinical meaningfulness of the result (correlation=-0.4431, p=0.0504 for absolute change, and correlation=-0.4474, p=0.0479 for % change in symptom severity, n=20).
Swallowing Quality of Life (SWAL-QOL) -- The well-validated SWAL-QOL questionnaire, specifically developed for patients suffering from problems in swallowing, demonstrated a statistically significant improvement in the mean reported symptom severity score from baseline through to 24 weeks. Total mean symptom severity score improved from 54.0 points at baseline to 61.4 points at 24 weeks (12.1% improvement), (p=0.0448, n=21).
Muscle Strength Tests -- The composite score of three lower extremity muscle strength tests showed a statistically significant improvement over baseline of 13.4% (p=0.0059, n=19). This composite reflects a statistically significant improvement of 13.9% in knee extension (p=0.0058), and 24.3% in foot extension (p=0.0381). Hip flexion did not achieve statistical significance but had a numerical improvement of 3.5% (p=0.4348).
The composite score of two upper extremity muscle strength tests (comprised of shoulder abduction and arm flexion) showed a numerical improvement of 12.9% versus baseline, but did not achieve statistical significance (p=0.0836, n=19).
Functional Muscle Tests -- The 30 second arm-lift test showed a statistically significant improvement of 17.6% (p=0.0191, n=18) while the 30 second sit-to-stand test showed a numerical improvement of 14.1% versus baseline (p=0.0682, n=18). Notably, this latter test showed a statistically significant improvement in absolute numbers with a p=0.0160. In the standard 4-stair climbing test, importantly, no deterioration was observed but there was no statistically significant improvement.
"We are encouraged by these interim results of the HOPEMD open label Phase 2 study," stated
"The totality of the data, with endpoints showing numerical and/or statistical improvement from baseline, gives us confidence that the proof of concept for Cabaletta in OPMD patients has been demonstrated," Dr. Megiddo concluded.
"The OPMD community currently has very limited treatment options and there is a critical unmet need for patients with this rare disorder," stated
"These results support our plan to move forward with a pivotal Phase 3 study in OPMD following pending meetings with regulatory authorities," said
"The interim results for OPMD, specifically with respect to dysphagia and muscle strength and function, give us insight into the potential of Cabaletta for use in other protein aggregation-related diseases, such as spinocerebellar ataxia type 3 (SCA3 or
HOPEMD Phase 2 Trial Design
The HOPEMD study is an open label Phase 2 multicenter study testing the safety, tolerability and efficacy of Cabaletta in patients suffering from OPMD. The study is being conducted at two centers –
Conference Call and Webcast Information
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Cabaletta is a chemical chaperone that protects against pathological processes in cells. It has been shown to reduce pathological aggregation of proteins within cells in several diseases associated with abnormal cellular-protein aggregation as well as acting as an autophagy enhancer. Cabaletta has been documented as demonstrating significant promise in preclinical animal models of OPMD, SCA3 and other PolyA/PolyQ diseases.
In OPMD, Cabaletta is being developed to prevent the aggregation of the pathological protein (PABPN1) in muscle cells, the hallmark of the disease, by stabilizing the protein, reducing the formation of protein aggregations, and promoting their clearance from cells through autophagy, thus preventing muscle cell death.
About Oculopharyngeal Muscular Dystrophy (OPMD)
OPMD is an inherited myopathy characterized by dysphagia (difficulty in swallowing) and the loss of muscle strength, and weakness in multiple muscles of the body. Symptoms generally appear in mid-life and get worse over time. As the dysphagia becomes more severe, patients become malnourished, lose significant weight, become dehydrated and suffer from repeated incidents of aspiration pneumonia. Aspiration pneumonia and severe emaciation are frequently the cause of death. The disease is caused by a genetic mutation responsible for the creation of a mutant unstable protein (PABPN1) that aggregates within patient muscle cells. There is currently no approved therapeutic treatment for OPMD.
About Spinocerebellar Ataxia Type 3 (SCA3)
SCA3, also known as
Established in 1983, the
BioBlast Pharma is a clinical-stage biotechnology company committed to developing clinically meaningful therapies for patients with rare and ultra-rare genetic diseases. The company is rapidly building a diverse portfolio of product candidates with the potential to address unmet medical needs for incurable diseases. The BioBlast platforms are based on deep understandings of the disease-causing biological processes, and potentially offer solutions for several diseases that share the same biological pathology. For more information please visit the Company's website, www.bioblast-pharma.com, the content of which is not incorporated herein by reference.