FDA approves Proteostasis’s triple combination program for CF

Singapore — Proteostasis Therapeutics, a clinical stage biopharmaceutical company dedicated to the discovery and development of ground-breaking therapies to treat cystic fibrosis (CF) and other diseases caused by dysfunctional protein processing, announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for the Company’s triple combination program for the treatment of cystic fibrosis. The Company’s proprietary triple combination includes a novel cystic fibrosis transmembrane conductance regulator (CFTR) amplifier, third generation corrector and potentiator, known as PTI-428, PTI-801 and PTI-808, respectively. The Company announced in January that the protocol for its triple combination clinical study, which the Company plans to initiate in the current quarter, has received endorsement and a high strategic fit score from the Therapeutics Development Network (TDN) and the Clinical Trial Network (CTN), the drug development arms of the Cystic Fibrosis Foundation (CFF) and the European CF Society (ECFS), respectively.

“Fast Track designation represents another positive step for the development of our triple combination therapy and underscores the serious unmet need that remains for the vast majority of CF patients,” said Meenu Chhabra, president and chief executive officer of Proteostasis Therapeutics.

The FDA’s Fast Track program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. An investigational drug that receives Fast Track program designation is eligible for more frequent communications between the FDA and the company relating to the development plan and clinical trial design and may be eligible for priority review if certain criteria are met.

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Steps in the Journey: CFTR mutation to sweat chloride concentration to survival

Associations between “salty” sweat and early mortality can be found in the scientific literature dating back to the 17th century [1], hundreds of years before a comprehensive medical description of cystic fibrosis (CF) [2]. Insightful observation of excessive dehydration and deaths among children during a 1948 New York City heat wave suggested that salt homeostasis was a fundamental cellular problem in CF [3], with identification of supranormal sweat chloride concentrations remaining fundamental to the diagnosis of CF today. Since identification of the mutated gene associated with CF (the cystic fibrosis transmembrane conductance regulator; CFTR) [4], pieces of the CF puzzle seem to have, for the most part, fallen into place. Continue reading Steps in the Journey: CFTR mutation to sweat chloride concentration to survival

Newly Discovered CF Mutations Could Be Why Some People with CF are Living Longer

Researchers hypothesize that the newly-discovered mutations help re-hydrate the airways, discouraging bacterial build-up in the lungs.

Despite a narrow average lifespan, there is a big range in how severely cystic fibrosis (CF) affects the lungs and other organs depending on an individual’s specific genetic variation, and even in how long patients sharing the same, most common genetic mutation are able to survive with CF.

This led researchers at Boston Children’s Hospital to wonder if other genetic mutations could be protective against CF’s effects. Recent findings published in the American Journal of Respiratory Cell and Molecular Biology suggest that may be the case.

“There are some patients at one end of extreme severity who need a lung transplant very early in life, then others whose clinical presentation seems to stabilize so that they can live into the fifth and sixth decades of life,” says Pankaj Agrawal, MBBS, MMSc, principal investigator and medical director of The Manton Center’s Gene Discovery Core at Boston Children’s, who was the co-first author on the study.

To find out why, Agrawal and researchers at Boston Children’s — including Ruobing Wang, MD, a pulmonologist, and Craig Gerard, MD, PhD, chief of the Division of Respiratory Diseases — conducted the first-ever longitudinal analysis of genetic modifiers related to CF.

They combed through a population of nearly 600 CF patients registered at the Boston Children’s Cystic Fibrosis Center and found five individuals who stood out because of their advanced age — in their 50s or 60s — and relatively normal lung function.

“Given the large size of our center’s patient population, we were able to find a number of individuals at this rare ‘extreme,'” says Wang, who was co-first author on the paper.

A new hypothesis for mitigating cystic fibrosis

To discover the genetic variants, the researchers collected blood from these patients and performed whole exome sequencing on their DNA, analyzing the “coding” section of the genome that is responsible for most disease-related mutations.

Sequencing the genes of these five Boston Children’s patients — a cohort known as “long-term non-progressors” — the researchers found a set of rare and never-before-discovered genetic variants that might help explain their longevity and stable lung function.

The gene variants are related to so-called epithelial sodium channels (ENaCs), semi-permeable cellular pathways responsible for reabsorbing sodium in the kidney, colon, lung and sweat glands.

“Our hypothesis is that these ENaC mutations help to rehydrate the airways of CF patients, making it less likely for detrimental bacteria to take up residence in the lungs,” says Wang.

The discovery brings ENaCs into the limelight as a potential new therapeutic target.

“For example, if we could target ENaCs with a small molecule or an antibody-based drug, we might be able to incur a protective effect against CF’s progression,” says Agrawal, who is also a physician in the Boston Children’s Division of Newborn Medicine.

Based on their findings, the team is now doing further studies to analyze the genetics of patients at the other end of the CF spectrum — those with extremely severe clinical presentation of symptoms at a young age.

Story Source:

Boston Children’s Hospital. “Some people with cystic fibrosis might live longer because of genetic mutations: Researchers hypothesize that the newly-discovered mutations help re-hydrate the airways, discouraging bacterial build-up in the lungs.” ScienceDaily. ScienceDaily, 25 October 2017. <https://www.sciencedaily.com/releases/2017/10/171025150620.htm>.

Materials provided by Boston Children’s HospitalNote: Content may be edited for style and length.

Positive Results for Phase 3 Studies of the Tezacaftor/Ivacaftor Combination Treatment

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced that the New England Journal of Medicine (NEJM) published two articles with results from two Phase 3 studies of the tezacaftor/ivacaftor combination treatment, a medicine in development that is designed to treat the underlying cause of cystic fibrosis (CF) in people ages 12 and older who have certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Continue reading Positive Results for Phase 3 Studies of the Tezacaftor/Ivacaftor Combination Treatment

Vertex Plans To Eradicate Cystic Fibrosis, And Go From There

Vertex Pharmaceuticals: Going From ‘Crisis’ To Blockbuster

Jeffrey Leiden, chief executive for Vertex Pharmaceuticals, plans to eradicate cystic fibrosis. (Vertex) Continue reading Vertex Plans To Eradicate Cystic Fibrosis, And Go From There

Two clinical trials presented at the European Cystic Fibrosis Conference

https://globenewswire.com/news-release/2017/08/17/1088301/0/en/Fluidigm-Licenses-CFTR-Next-Generation-Sequencing-Assay-From-Baylor-Genetics-for-Use-With-the-Juno-System.html

ProQR Announces Results for the Second Quarter of 2017

Key updates
• Data from two clinical trials of QR-010 presented at the European Cystic Fibrosis Conference. Enrollment completed in the Phase 1b clinical trial in cystic Continue reading Two clinical trials presented at the European Cystic Fibrosis Conference

New cystic fibrosis biotech aims to take a different approach than Vertex

http://www.bizjournals.com/

California-based Synedgen has spun out its experimental cystic fibrosis treatments into a new biotech to be based in the Boston area, with an eye toward complementing existing drugs for the lung disease. Continue reading New cystic fibrosis biotech aims to take a different approach than Vertex

Potential new treatment for cystic fibrosis uncovered

http://www.medicalnewstoday.com/articles/316837.php

Cystic fibrosis is an inherited disease that affects tens of thousands of people in the United States and worldwide. There is currently no cure for the condition, but new research proposes a novel therapeutic approach that may soon stop the disease from progressing. Continue reading Potential new treatment for cystic fibrosis uncovered

Support of Clinical Candidate for Cystic Fibrosis from Sprynx Biosciences

Spyryx Biosciences Presents Data and Corporate Update at Two Recent Conferences in Support of Clinical Candidate for Cystic Fibrosis

– Provides corporate update at Needham Healthcare Conference

– Highlights positive data & mechanism of action of SPX-101 at
ECFS Basic Science Conference Continue reading Support of Clinical Candidate for Cystic Fibrosis from Sprynx Biosciences