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

Study Links PPI Use to Treat Gastroesophageal Reflux with More Frequent Hospitalizations

Doctors should frequently re-evaluate the use of protein pump inhibitors (PPIs) for cystic fibrosis (CF) patients, urges a University of Florida study which warns that long-term PPI use leads to a higher risk of hospitalization for pulmonary exacerbations.

Identifying risk factors associated with pulmonary exacerbations is critical since they cause a decline in pulmonary function and survival rates among CF patients.

PPI use, in particular, is believed to cause community-acquired pneumonia (CAP). Even though most CF patients use PPIs to control gastroesophageal reflux (GER), scientists still don’t fully understand the link between PPIs and pulmonary exacerbations in CF.

In the study, “Proton Pump Inhibitor Use Is Associated With an Increased Frequency of Hospitalization in Patients With Cystic Fibrosis,” which appeared in the journal Gastroenterology Research, researchers investigated that link and the risks it entails.

The study involved 114 adults who had been seen at UF’s Adult Cystic Fibrosis Center in Gainesville, Florida, between January and December 2016. Researchers collected data on PPI use and hospitalization during a one-year follow-up.

Results showed that 59 of the 114 patients (51.7 percent) used PPI for six or more months, and that exactly the same proportion (51.7 percent) had been hospitalized at least once during the one-year follow-up period. Among those who were hospitalized, PPI use was closely linked with the number of hospitalizations for pulmonary exacerbation, though researchers observed no link between frequency of hospitalization and PPI dosage.

No significant difference was found in GER between hospitalized and non-hospitalized patients.

The UF study is limited, in that it’s retrospective and therefore doesn’t establish a cause-effect relationship between PPIs and pulmonary exacerbation. Researchers say there’s still a possibility that GER itself — rather than the subsequent use of PPIs — causes increased pulmonary exacerbations. Yet they point out that the prevalence of GER was similar among hospitalized and non-hospitalized patients, supporting a causative link between PPI and pulmonary exacerbations.

Based on their findings, the UF team suggests that “prescribers of PPI therapy should exercise pharmacovigilance; frequently re-evaluating indications and appropriateness of therapy and in the setting of GER considering alternate management modalities such as anti-reflux surgery where appropriate.”

For original article please visit: https://cysticfibrosisnewstoday.com/2017/12/07/proton-pump-inhibitor-use-is-associated-with-an-increased-frequency-of-hospitalization-in-patients-with-cystic-fibrosis/

Trial to Possibly Treat Nonesense Mutations Begins

Sevion Therapeutics and Eloxx Pharmaceuticals announced that a first healthy subject has been dosed in a Phase 1b clinical trial assessing the safety, tolerability and drug properties of ELX-02 as a potential treatment of several genetic diseases caused by nonsense mutations, including cystic fibrosis (CF).

Continue reading Trial to Possibly Treat Nonesense Mutations Begins

A Brief Historical Timeline of CF Research to Date

Cystic fibrosis care has seen such rapid advances that the average CF patient has experienced a dramatic evolution in treatment strategies in their lifetime. Here are some of the biggest milestones that shaped modern-day CF treatments.

Continue reading A Brief Historical Timeline of CF Research to Date

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

PBS’s Documentary ‘The Gene Doctors’ Arrives Amid A Gene Therapy Boom

Molly Troxel, who has an inherited degenerative eye disease, regained some vision after being treated with Spark’s experimental gene therapy, Luxturna. (Photo courtesy of PBS.)

This month, PBS is airing a documentary called The Gene Doctors that spotlights several emerging gene therapies, Continue reading PBS’s Documentary ‘The Gene Doctors’ Arrives Amid A Gene Therapy Boom

Biopharmaceutical company developing novel small molecule medicines for genetic diseases caused by nonsense mutations

http://markets.businessinsider.com/news/stocks/Eloxx-Pharmaceuticals-Announces-Expansion-of-Intellectual-Property-Estate-for-ELX-02-with-Newly-Granted-Patent-in-Europe-1004482616

Eloxx Pharmaceuticals Announces Expansion of Intellectual Property Estate for ELX-02 with Newly Granted Patent in Europe

Sevion Therapeutics, Inc. (OTCQB:SVON) and Eloxx Continue reading Biopharmaceutical company developing novel small molecule medicines for genetic diseases caused by nonsense mutations

New Inhaled Antibiotic To Treat Respiratory Infections

https://www.europeanpharmaceuticalreview.com/news/67983/polyphor-antibiotic-murepavadin/

Polyphor launches the development of an inhaled antibiotic murepavadin

Polyphor Ltd has announced the development of an inhaled dosage form of its break­through antibiotic Murepavadin. Continue reading New Inhaled Antibiotic To Treat Respiratory Infections

Microbiologists uncover clues to clustering of lethal bacteria in CF patients’ lungs

ahttps://www.eurekalert.org/pub_releases/2017-10/iuui-imu100517.php

IUPUI microbiologists uncover clues to clustering of lethal bacteria in CF patients’ lungs

Individuals with cystic fibrosis, or CF, have a high risk of chronic pneumonia because the thick, sticky mucus that builds up in Continue reading Microbiologists uncover clues to clustering of lethal bacteria in CF patients’ lungs

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