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.

To read original article click here.

Antibiotic resistance evolution of Pseudomonas aeruginosain cystic fibrosis patients

By Francesca Lucca, Margherita Guarnieri, Mirco Ros, Giovanni Muffato, Roberto Rigoli, and Liviana Da Dalt

Below is a study hoping to define and answer the questions of Pseudomonas aeruginosain, its evolution and the resistance from different antibiotics. The study took place between 2010-2013. Though the study may have some time clauses I believe there are some strong findings for the CF community moving forward.
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Introduction

Pseudomonas aeruginosa is the predominant pathogen responsible of chronic colonization of the airways in cystic fibrosis (CF) patients. There are few European data about antibiotic susceptibility evolution of P aeruginosa in CF patients.

Objectives

The aim of this study is to evaluate the evolution of antibiotic resistance in the period 2010‐2013 in CF patients chronically colonized by P aeruginosa and to highlight the characteristics of this evolution in patients younger than 20 years.

Methods

Clinical and microbiological data were extracted from two electronic databases and analyzed. Antibiotic resistance was defined according to European Committee of Antimicrobial Susceptibility Testing for levofloxacin, ciprofloxacin, meropenem, amikacin and ceftazidime. The between‐group comparison was drawn with the Chi‐square test for proportions, with the T‐test for unpaired samples for normally distributed data and with Mann‐Whitney test for non‐normally distributed data. Significancy was defined by P < .05.

Results

Fifty‐seven CF patients, including thirteen subjects aged less than 20 years, were enrolled. P.. aeruginosa antibiotic sensitivity decreased significantly for fluoroquinolones, mainly in patients aged <20 years, while it increased for amikacin and colistin. The analysis of minimum inhibitory concentration confirmed these trends. In pediatric patients treated with more than three antibiotic cycles per year, greater resistance was found, except for amikacin and colistin.

Conclusion

An evolution in P aeruginosa antibiotic resistances is observed in the 4‐year period studied. Responsible and informed use of antibiotics is mandatory in CF.
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Read the whole clinical journal here. 

Antibiotic resistance evolution of Pseudomonas aeruginosa in cystic fibrosis patients (2010‐2013) Francesca Lucca,Margherita Guarnieri,Mirco Ros,Giovanna Muffato,Roberto Rigoli,Liviana Da Dalt. First published: 1 April 2018. https://doi.org/10.1111/crj.12787

Potential Nitric Oxide Treatment for Resistant Bacterial Infections Gets Patent

A possible inhalable treatment for antibiotic-resistant bacterial infections in people with cystic fibrosis due to Pseudomonas aeruginosa now has a U.S. patent and is being readied for a first clinical trial, Novoclem Therapeutics announced.

The patent (No. 9,850,322) was issued to the University of North Carolina (UNC) at Chapel Hill where the potential therapy, BIOC51, was discovered, and covers a technology known as water-soluble polyglucosamine compositions that release nitric oxideContinue reading Potential Nitric Oxide Treatment for Resistant Bacterial Infections Gets Patent

Clinical Trial Opportunity for Phase IV Airway Clearance System

Med Systems is sponsoring a Phase IV clinical study to measure the
effectiveness of the Electro Flo 5000 Airway Clearance System for
people who have been diagnosed with cystic fibrosis. The goal of the
study is to provide health insurers and Medicare with comprehensive
information regarding the system’s performance. The study is designed
to measure the efficacy of the system, which includes the FDA510K
(K031876) device under current indications. The study will last 30 days
and involve using the system for lung clearance and recording the
results in a digital journal. The study should take about 10 minutes per
day to record measured results in the morning after waking. You will
also be asked to use a spirometer and a digital pulse oximeter to
evaluate your lung function after using the Electro Flo 5000 Airway
Clearance System.

Interested participants must be:
 Between the ages of 18-55 years of age
 Diagnosed with cystic fibrosis
 Prescribed chest physical therapy for airway clearance
 Able to perform self-treatment- having manual dexterity
 Residing in the United States

Contact- Dr. Leigh Mack: CFtrial@mackbio.com or Phone 888-935-
8676 ext. 706

Therapy for Reducing P. Aeruginosa Lung Infections Planned Phase 1 Trial

Arch Biopartners recently completed a good manufacturing practice (GMP) production campaign for AB569, a potential inhalation treatment for antibiotic-resistant bacterial lung infections in people with cystic fibrosis (CF) chronic obstructive pulmonary disease (COPD) and other conditions. The campaign, intended to ensure the quality of the investigative therapy, was directed by Dalton Pharma Services.

AB569 is composed of ethylenediaminetetraacetic acid (EDTA) and sodium nitrite, two compounds approved by the U.S. Food and Drug Administration (FDA) for use in people. AB569 can be administered alone or in combination with other compounds to treat multi-drug resistant bacterial infections that can cause reduced lung function.

Pseudomonas aeruginosa is one of the most common bacterial infections in patients with respiratory diseases, including CF, COPD, and pneumonia.

In preclinical studies, AB569 was shown to be capable of killing drug-resistant bacteria like P. aeruginosa and other common pathogens associated with chronic lung infections.

The company also announced that a Phase 1 clinical trial to investigate the safety and pharmacokinetic profile of AB569, planned to start in January, will be conducted at the Cincinnati Veterans Affairs Medical Center (CVAMC). According to an Arch Biopartners press release, Ralph Panos, chief of medicine at CVAMC, will lead the trial.

Three escalating doses of nebulized AB569 will be used to evaluate tolerance to the treatment in about 25 healthy volunteers. Each will be given a single administration of nebulized AB569  to characterize the pharmacokinetic profile of plasma nitrite and nitrate metabolites, exhaled nitric oxide, and circulating hemoglobin.

Pharmacokinetics studies how a drug is absorbed, distributed and metabolized in, and expelled by, the body.

Should the Phase 1 trial in volunteers be successful, Arch Biopartners plans to move its AB569 program into a Phase 2 trial to test its effectiveness in treating chronic P.aeruginosa infections in COPD patients.

AB569 received orphan drug status by the FDA in November 2015 as a potential treatment of P. aeruginosa lung infections in CF patients. Orphan drug status is given to investigative medicines intended for people with rare diseases to speed their development and testing.

Original article: https://cysticfibrosisnewstoday.com/2017/12/12/arch-biopartners-readies-ab569-potential-treatment-for-cf-copd-lung-infections-for-phase-1-trial/

New Promising Results from Phase 3 of Combination Therapy

Findings from a phase 3 trial evaluating the efficacy and safety of tezacaftor in combination with ivacaftor in patients with cystic fibrosis (CF) who were homozygous for the Phe508del mutation were published in the New England Journal of Medicine.

The Phe508del mutation has been known to result in greatly reduced conductance regulator (CFTR) protein activity and a loss of chloride secretion, which can lead to impaction of mucus in the airways, gastrointestinal tract, and exocrine organs, with the potential for severe clinical consequences including gradual loss of lung function, nutritional deficits, pulmonary exacerbations, and respiratory failure. It is the most prevalent CFTR mutation worldwide, and affects approximately 46% of American CF patients.

Previous data has shown Ivacaftor’s association with a rate of progressive decline in lung function that is lower than that in untreated patients. In a phase 2 clinical trial involving patients who were homozygous for the Phe508del mutation or heterozygous for the Phe508del and G551D mutations, when combined with the investigational CFTR corrector tezacaftor, it has exhibited enhanced CFTR function and improved lung function.

In August, just one month removed from Vertex’s announcement of positive datafrom Phase 1 and Phase 2 studies, Rare Disease Report covered the acceptance of applications for the use of the tezacaftor/ivacaftor combination treatment in this patient population by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).

The phase 3 trial enrolled a total of 510 patients 12 years and older with CF who were homozygous for the Phe508del CFTR mutation at 91 sites in the U.S., Canada, and Europe from January 30, 2015 to January 20, 2017. Patients were randomly assigned to be administered either tezacaftor and ivacaftor (administered as a fixed-dose combination tablet containing 100 mg of tezacaftor and 150 mg of ivacaftor in the morning and a tablet containing 150 mg of ivacaftor in the evening) combination therapy or placebo for 24 weeks.

In total, 475 patients completed the full 24 weeks of the trial, with 93.6% (n=235) in the tezacaftor-ivacaftor group and 93% (n=240) in the placebo group. While no significant difference in the body mass index (BMI) was experienced between the groups at week 24, the use of the combination therapy led to a significantly greater absolute change from baseline in the predicted forced expiratory volume in 1 second (FEV1) than placebo. Despite advances in standard-of-care therapy, patients with CF continue to lose lung function at a rate of an estimated 1% to 3% per year. This trial exhibited a significant effect of the combination therapy compared to the placebo, as the mean absolute change from baseline in FEV1 through week 24 was 3.4 percentage points in the former, compared to 0.6 in the latter.

The most common adverse events (AEs) among the enrolled patients included infective pulmonary exacerbation, cough, headache, nasopharyngitis, increased sputum production, pyrecia, hemoptysis, oropharyngeal pain, and fatigue. The incidence of AEs was similar in both the group for combination therapy and the placebo group, however, those treated with lumacaftor-ivacaftor in the phase 3 did not experience an increased incidence of respiratory events (33 patients [13.1%] vs. 41 patients [15.9%]).

This improved safety profile of the tezacaftor-ivacaftor combination supports its use in a broad range of patients with CF, and, if approved, the therapy will be the third of Vertex’s drugs approved for CF patients, and the second intended specifically to treat patients with F508del mutations (Orkami [lumacaftor/ivacaftor]).

For original article please visit: http://www.raredr.com/news/phase-3-combination-therapy-cystic-fibrosis?t=physicians

For the published study please visit: http://www.nejm.org/doi/full/10.1056/NEJMoa1709846?query=genetics#t=articleDiscussion

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

Live Stream the North American CF Conference Tomorrow for Free!

The North American CF Conference (NACFC) provides a collaborative and educational forum for all CF professionals. The educational elements of the meeting program are targeted to physicians, nurses, research scientists, respiratory therapists, physical therapists, nutritionists, social workers, and pharmacists. Continue reading Live Stream the North American CF Conference Tomorrow for Free!

Phase 1a study for drug to treat CF regardless of CF Mutation

http://www.businesswire.com/news/home/20171018005403/en/Synspira-Announces-Patient-Dosed-Phase-1a-Study

Synspira Announces First Patient Dosed in Phase 1a Study of SNSP113 in Cystic Fibrosis
— First-in-class drug candidate for treatment of cystic fibrosis regardless of genetic mutation — Continue reading Phase 1a study for drug to treat CF regardless of CF Mutation

Antifungal Drug Candidate Receives a Second “Qualified Infectious Disease Product” Designation

Pulmatrix Antifungal Drug Candidate Receives a Second “Qualified Infectious Disease Product” (QIDP) Designation from the FDA

http://markets.businessinsider.com/news/stocks/Pulmatrix-Antifungal-Drug-Candidate-Receives-a-Second-Qualified-Infectious-Disease-Product-QIDP-Designation-from-the-FDA-1002944255 Continue reading Antifungal Drug Candidate Receives a Second “Qualified Infectious Disease Product” Designation