Release time: November 9, 2020, Gail Dutton (Gail Dutton)

IntraBio initiated the Phase II extension study of IB1001 (N-acetyl-L-leucine) shortly after announcing the positive results of the preliminary "maternal" cross-country trial for Niemann-Pick Disease Type C (NPC). The extended study aims to evaluate the neuroprotective and disease-relief effects of the drug. The company plans to contact the FDA in the next few weeks, hoping to obtain approval for the drug based on the symptom relief shown in the initial "parent company" study.

The parental study showed that the clinical impression of the severity change has undergone a statistically significant change. Specifically, the study reports improvements in gait, fine motor skills, language, cognition, overall function, and quality of life. It also met secondary endpoints, including the Ataxia Assessment Scale (SARA) and the researcher’s clinical overall impression of change (CGI-C), thus demonstrating significant improvement in patients during the six-week trial and the subsequent six-week trial . Week flush period.

For example, a dramatic video shows children getting up from a wheelchair for the first time, or eventually trying to eat on their own.

"This is a big deal, but a six-week study does not prove disease changes and neuroprotective effects," Mallory Factor, founder and CEO of IntraBio, told BioSpace. The basic principle of IB1001's disease-improving effect is strongly supported by early non-clinical studies in the NPC mouse model, as well as the results of the long-term clinical case series of NPC.

The 12-month expansion phase of the study will address these endpoints, 13.5 months after the patient completes the maternal study (12 months of treatment, followed by a 6-week washout period). Thirty-three patients between the ages of 7 and 64 completed parental studies at nine locations in the United States, the United Kingdom, and the European Union, including the Mayo Clinic.

NPC is a rare prematurely fatal autosomal recessive lysosomal storage disease. It is a chronic progressive disease that begins in early childhood and is characterized by rapid degeneration of the cerebellum and major organ systems. It manifests as systemic, mental and neurological symptoms.

Regardless of the results of the extended study, even providing symptom relief is an important step forward. Currently, there is no approved treatment for NPC in the United States. In the European Union and some other countries, treatment is limited to the substrate-reducing drug migrulinast (Zavesca™).

As Susanne Schneider, MD, principal researcher at Ludwig Maximilian University in Munich said in a statement, “BI1001 is a breakthrough in the NPC patient community. IB1001 is statistically significant in terms of primary and top-line secondary endpoints. The significant and clinically significant response, along with its convincing safety and ease of oral administration [pouches mixed with water], confirms the very favorable risk/benefit profile of IB1001 as a treatment for this devastating disease."

Jocelyn Crowe, executive director of the National Niemann-Pick Disease Foundation, agreed.

"The exciting results of the IB1001 clinical trial have brought a new level of hope and optimism to patients and families affected by Niemann-Pick disease type C," said Crowe. "New therapies for the treatment of NPC are urgently needed."

IntraBio focuses on neurodegenerative diseases-especially lysosomal storage diseases.

"These diseases have the same mechanism of action as Alzheimer's disease, but they are very rare," Factor said. For example, NPC affects 1:100,000 live births. This rarity allows the company to conduct small clinical trials for "people with very bad health." Usually, there is no medically available method. "

Lysosomal storage disease is a congenital metabolic error that causes large molecules to accumulate or store in the late endocytic system. In NPC1, late endosome and lysosome mutations lead to accumulation of sphingosine, glycosphingolipid, sphingomyelin and cholesterol. More simply, Factor explains, “Many neurodegenerative diseases are caused by the accumulation of neurons in lysosomes, which are essentially trash cans for cells.” This happens when the trash can is not emptied. confusion. Cell signals cannot pass.

In mouse studies, acetyl-DL-leucine and its enantiomers acetyl-L-leucine and acetyl-D-leucine have been shown to slow down the disease progression of nasopharyngeal carcinoma and other lysosomal diseases . Factor says that basically, IB1001 clears accumulated neurons from the lysosome.

"There are about 70 lysosomal storage diseases. So far, IB1001 has been used in more than 18 indications in the past ten years, including six cases of dementia. This is a very simple molecule that can be worn It crosses the brain blood barrier and can be taken orally and is safe."

IB1001 is also in multinational trials for GM2 gangliosidosis (Tay-Sachs and Sandhoff)-expected to be released in early 2021-and for ataxia telangiectasia (AT) in the United States and the European Union- Also known as the Louis-Bar syndrome in the trial. Preclinical studies have shown that it may also be beneficial in the treatment of chronic traumatic encephalopathy, and according to its mechanism of action, may help treat Alzheimer's disease.

"Our main goal is to provide IB1001 to patients as soon as possible," Factor said. "The product is manufactured, but it is not labeled."

In terms of commercialization, he said the company is open to choice.

© 1985-2021 BioSpace.com. all rights reserved. Supported by Madgex work board software