Vertex Employees Donate $1M to CF and Other Communities via Matching Gift Program

By Carolina Henriques

Vertex Pharmaceuticals employees have raised more million $1 million  using  the Vertex Foundation‘s matching gift program in a show of commitment to causes that include the cystic fibrosis (CF) community, a company press release states.

The dollar-for-dollar matching gift program is being run through the nonprofit Vertex Foundation, established by the company in November 2017 as part of it’s charitable giving goal of donating $500 million to qualified nonprofits and other causes worldwide over 10 years.

To date, more than 500 Vertex employees have used the program to support 753 charities around the globe working to advance work in areas that include healthcare, human services, education, and disaster relief.

Vertex’s charitable commitment has four primary goals: supporting CF patients and caregivers worldwide, including enabling access to Vertex’s medicines; helping underserved students and young women with STEAM (science, technology, engineering, arts and math) education; supporting young doctors and scientists; and strengthening and fostering innovation in local communities through health and wellness programs.

“Giving back is in our DNA at Vertex, and our employees have a long history of going the extra mile to improve the lives of patients, students and their neighbors,” Jeffrey Leiden, president, chairman and chief executive officer of Vertex, said in the release. “I’m proud that The Vertex Foundation is able to help extend the impact of our employees’ giving and look forward to seeing the reach of these investments in the causes they care about most.”

Also as part of its 10-year commitment, Vertex awarded $400,000 in scholarships to eligible CF patients and their family members in May as part of its second “All in for CF” scholarship program. In total, 80 scholarships worth $5,000 each were awarded for the upcoming academic year.

Vertex, which specializes in cystic fibrosis, has three approved CF therapies: Kalydeco (ivacaftor), Orkambi (lumacaftor/ivacaftor), and Symdeko (tezacaftor/ivacaftor).

The company is also testing potential triple combination treatments for CF.

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Toothpaste ingredient may bust up cystic fibrosis biofilms

By Chris Waters and Sarina Gleason

A common antibacterial substance in toothpaste may combat life-threatening diseases such as cystic fibrosis when combined with an with an FDA-approved drug, researchers report.

Researchers have found that when triclosan, a substance that reduces or prevents bacteria from growing, combines with an antibiotic called tobramycin, it kills the cells that protect the CF bacteria, known as Pseudomonas aeruginosa, by up to 99.9 percent.

CF is a common genetic disease with one in every 2,500 to 3,500 people diagnosed with it at an early age. It results in a thick mucus in the lungs, which becomes a magnet for bacteria.

These bacteria are notoriously difficult to kill because a slimy barrier known as a biofilm, which allows the disease to thrive even when treated with antibiotics, protects them.

“The problem that we’re really tackling is finding ways to kill these biofilms,” says Chris Waters, lead author of the study and a microbiology professor at Michigan State University.

According to Waters, there are many common biofilm-related infections that people get, including ear infections and swollen, painful gums caused by gingivitis. But more serious, potentially fatal diseases join the ranks of CF including endocarditis, or inflammation of the heart, as well as infections from artificial hip and pacemaker implants.

Waters and his coauthors grew 6,000 biofilms in petri dishes, added in tobramycin along with many different compounds, to see what worked better at killing the bacteria. Twenty-five potential compounds were effective, but one stood out.

“It’s well known that triclosan, when used by itself, isn’t effective at killing Pseudomonas aeruginosa,” says coauthor Alessandra Hunt, a postdoctoral associate of microbiology and molecular genetics. “But when I saw it listed as a possible compound to use with tobramycin, I was intrigued. We found triclosan was the one that worked every time.”

Triclosan has been used for more than 40 years in soaps, makeup, and other commercial products because of its antibacterial properties. Recently, the FDA ruled to limit its use in soaps and hand sanitizers due to insufficient data on its increased effectiveness and concern about overuse. Clear evidence has shown, though, that its use in toothpaste is safe and highly effective in fighting gingivitis, and it is still approved for use.

“Limiting its use is the right thing to do,” says coauthor Michael Maiden, a graduate student in medicine. “The key is to avoid creating resistance to a substance so when it’s found in numerous products, the chances of that happening increase.”

Tobramycin is currently the most widely used treatment for CF, but it typically doesn’t clear the lungs of infection, Waters says. Patients typically inhale the drug, yet still find themselves chronically infected their whole lives, eventually needing a lung transplant.

“Most transplants aren’t a viable option though for these patients and those who do have a transplant see a 50 percent failure rate within five years,” he says. “The other issue is that tobramycin can be toxic itself.” Known side effects from the drug include kidney toxicity and hearing loss.

“Our triclosan finding gives doctors another potential option and allows them to use significantly less of the tobramycin in treatment, potentially reducing its use by 100 times,” Hunt says.

Within the next year, Waters and his colleagues will begin testing the effectiveness of the combination therapy on mice with hopes of it heading to a human trial soon after since both drugs are already FDA approved.

Just brushing your teeth with toothpaste that has triclosan won’t help to treat lung infections though, Maiden says.

“We’re working to get this potential therapy approved so we can provide a new treatment option for CF patients, as well as treat other biofilm infections that are now untreatable. We think this can save lives,” he says.

The research appears in the journal Antimicrobial Agents and Chemotherapy.

The National Institutes of Health, Cystic Fibrosis Foundation, and Hunt for a Cure in Grand Rapids, Michigan funded the research.

Source: Michigan State University

CF Foundation ‘Venture Philanthropy’ Model Crucial to CF Breakthroughs

By Larry Luxner

When the Cystic Fibrosis Foundation (CFF) was established in 1955, most people with cystic fibrosis (CF) didn’t make it to their sixth birthday. Today, the average life expectancy of a CF patient is 47 years.

To date, the U.S. Food and Drug Administration has approved 12 CF therapies. Three of them are CFTR modulators that treat the basic disease-causing defect, benefiting 60 percent of all patients, and more therapies are on the way.

Preston W. Campbell III, the CFF’s president and CEO, directly attributes this dramatic improvement to the foundation’s philosophy of “venture philanthropy.”

“We are now in Phase 3 CFTR trials that, if successful, will mean that as early as next year, more than 90 percent of all individuals with CF will have a highly effective therapy targeting CF’s basic defect,” he said. “More therapies that treat the complications of CF are in the pipeline than ever before.

“It begs the question: how did all of this happen?”

Campbell answered that during his March 26 presentation, “Patient advocates taking a real stand in drug development: How the CFF worked with biotech and pharma to find a cure,” at the 2018 World Orphan Drug Congress USA in Oxon Hill, Maryland.

Back in 1960, the Bethesda, Maryland-based foundation broke ground by establishing a Care Center Network to provide multidisciplinary care. Within five more years, it had formed a patient registry.

With only $400,000 in the bank, it would also commit $11 million to research, Campbell said. “Five years later, in 1985, the basic CF defect was identified, and in 1989, the CFTR gene was discovered. That opened the floodgates,” he added.

Campbell’s predecessor, Robert J. Beall, created the Therapeutics Development Program — now called its Venture Philanthropy Model — in 1998 to entice industry to focus on CF, and specifically on CFTR as a target. Its three components were financial assistance, research tools and scientific advice, and a clinical trials network.

“We would lower the risk for industry to come into the CF space. We also made our research tools and scientific advice freely available, and we also embedded the best scientists in the world in these industry programs,” said Campbell, who took over from Beall as head of the CFF in January 2016. “Finally, in order to make sure clinical trials were safely and efficiently done, we created a clinical trials network that originally had seven centers and now has 89.”

In the beginning, CFF’s investments were typically in the $1.5 million range. Ultimately, the foundation invested more than $100 million in Aurora and its successor, Vertex Pharmaceuticals, whose headquarters are in Boston.

To date, the FDA has approved three Vertex CFTR modulators: Kalydeco (ivacaftor) for patients with the G551D mutation in the CFTR gene (2012); Orkambi (lumacaftor/ivacaftor)for patients who are homozygous for F508del, the most common mutation in the CFTR gene (2015); and Symdeko (tezacaftor/ivacaftor) for homozygous F508del patients as well as others (2018).

“Payments are milestone-based, so we pay for success,” Campbell said. “A scientific advisory committee determines if milestones are met and if the project should continue. Successful programs offer a return on our investment, so if the program is foundering, we shake hands and walk away.”

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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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A Dutch Company on the Quest Against Cystic Fibrosis

An interview by:  Clara Rodríguez Fernández

Daniel de Boer founded ProQR in 2012 following a strong determination to improve the lives of people with cystic fibrosis. We started ProQR Therapeutics for a very personal reason,” he told me. “Eight years ago, my son was born, and diagnosed with cystic fibrosis. At that time, I was a serial entrepreneur in IT. I decided to make a career switch and start a company to develop drugs for cystic fibrosis, but then also for other genetic diseases.”

One would think that a person without a background in biotech might have it difficult to succeed, but de Boer is not the only to have so far successfully undertaken this endeavor. Over in France Karen Aiach built Lysogene to treat her daughter’s rare genetic disorder, while in the US the story of John Crawley and his company Amicus Therapeutics, founded to help his two children’s diagnosis, went so far as to inspire a movie. The determination and motivation of these parents seem to overdrive any challenges they might have faced because of their limited experience.

De Boer set out to create a business plan for his new company and found out that there was already quite a lot of activity, especially in approaches using small molecules or gene therapy.“We decided that we really wanted to add something new to the space, and take a completely novel approach.”

So he started looking for a new technology, and he found it. “Around that time, I met for the first time with some people in biotech, including the CEO at Alnylam, John Maraganore, and we talked about how they used RNA approaches for genetic diseases,” says de Boer.

Technologies targeting RNA are quite new compared to those that target DNA such as gene therapy. But RNA-based treatments have started to gain traction in the last few years. There are multiple ways that RNA can be used as a therapeutic, but its distinctive advantage over gene therapies and the likes is that it does not permanently change our genetic makeup, making it possible to reverse its effects.

Today, RNA technology is being tested in multiple rare diseases caused by genetic mutations, such as hemophilia, porphyria, or iron overload disorders. I thought, ‘if you can do that for all these other genetic diseases, why not for cystic fibrosis?’” says the Boer. “With that in mind, we started ProQR.”

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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

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