Positive Data from the CARE CF 1 Clinical Study of Oral Lynovex in Cystic Fibrosis Exacerbations

NovaBiotics Ltd (“NovaBiotics”) announces that its oral therapy for cystic fibrosis (CF), Lynovex®, has met the study objectives of the CARE CF 1 clinical trial.

CARE CF 1 assessed the effects of two weeks of Lynovex treatment as an adjunct to standard of care therapy (SOCT) in CF, compared to placebo plus SOCT. This trial was designed to determine whether the inclusion of Lynovex capsules alongside SOCT lessened the clinical impact of exacerbations in adults with CF, as measured by symptom severity and levels of bacteria and inflammatory mediators in sputum and blood.  CARE CF 1 was a 6-arm study with the primary objectives of determining the optimal dose and regimen of Lynovex in patients with exacerbations of CF-associated lung disease and to further evaluate the safety and tolerability of Lynovex in exacerbating CF patients.  Continue reading Positive Data from the CARE CF 1 Clinical Study of Oral Lynovex in Cystic Fibrosis Exacerbations

A Drug Costs $272,000 a Year. Not So Fast, Says New York State.

From The New York Times:

A Drug Costs $272,000 a Year. Not So Fast, Says New York State.

New York’s Medicaid program says Orkambi, a new drug to treat cystic fibrosis, is not worth the price. The case is being closely watched around the country.

A wave of breakthrough drugs is transforming the medical world, offering hope for people with deadly diseases despite their dizzying price tags.

But what if it turns out that some of these expensive new drugs don’t work that well?

That’s the quandary over Orkambi, a drug that was approved in 2015 for cystic fibrosis and was only the second ever to address the underlying cause of the genetic disease. Orkambi, which is sold by Vertex Pharmaceuticals, costs $272,000 a year, but has been shown to only modestly help patients.

Now, in a case that is being closely watched around the country, New York state health officials have said Orkambi is not worth its price, and are demanding that Vertex give a steeper discount to the state’s Medicaid program. The case is the first test of a new law aimed at reining in skyrocketing drug costs in New York’s Medicaid program.

The high price of prescription drugs has ignited a populist furor, and in May, the Trump administration unveiled a set of proposals to address the issue. But while the ideas at the federal level are still mostly theoretical, some states have begun tackling the issue themselves. Earlier this year, Massachusetts asked the federal government for permission to limit its coverage of drugs in an effort to secure larger discounts from drug makers. Other states, like California and Vermont, have passed laws requiring drug companies to turn over certain financial details if they raise prices significantly.

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“There’s a number of states that are really trying to push forward and say, we need to be thinking very differently about how we’re paying for drugs,” said Matt Salo, the executive director of the National Association of Medicaid Directors. “We need the ability to say that there are some drugs that are just not priced in a rational way.”

Orkambi held great promise for people with cystic fibrosis when it was approved three years ago. A similar drug, Kalydeco, approved in 2012, was viewed as groundbreaking because it was the first to try to counteract the genetic defect that causes cystic fibrosis. The disease, which affects about 30,000 Americans, leads to a buildup of sticky mucus in the lungs and can lead to death by respiratory failure by the time many people are 40.

But while Kalydeco, also known as ivacaftor, was found to be effective, it was only approved for a sliver of patients with the disease — those who had certain genetic mutations. Orkambi, which combines ivacaftor and another drug, lumacaftor, was approved for mutations that covered nearly half of cystic fibrosis patients, but studies showed it was not as effective as Kalydeco.

Since Orkambi’s approval, several countries have balked at paying for it, including Britain, France and Canada.

In the United States, private insurers and Medicare plans have generally covered Orkambi. Medicaid programs, which cover health insurance for the poor, are required to cover all drugs.

Still, many insurers require patients to pay thousands of dollars out of pocket, and even though Vertex offers assistance, not everyone qualifies.

Lora Moser, 40, is covered by Medicare because she is disabled, and said she had to stop taking Orkambi in January because she could not afford the first month’s payment of more than $3,000 required by her insurer, Humana. A spokeswoman for Humana said that for high-cost drugs like Orkambi, the insurer helps patients identify outside assistance programs to cover out-of-pocket costs.

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Ms. Moser said a nonprofit group that had provided financial assistance declined to renew her grant because, she said she was told, her annual household income was too high.CreditTamir Kalifa for The New York Times

A nonprofit group that had provided assistance the previous year to Ms. Moser declined to renew her grant because, she said she was told, her annual household income was too high. She said her income is about $600 above their limit.

“I’ve never felt more destitute and hopeless as I do right now, from a medical standpoint,” Ms. Moser said.

A spokeswoman for Vertex, Heather Nichols, said more than 99 percent of cystic fibrosis patients who are eligible to take Orkambi in the United States have “broad access” to the drug.

“Vertex has a longstanding commitment to supporting access for all eligible patients, and we will continue to oppose any attempts to restrict patient access to these transformative medicines,” Ms. Nichols said.

Despite its lukewarm reception, Orkambi has been a boon for Vertex. In 2017, the drug was its top-selling product, bringing in about $1.3 billion in sales, a considerable sum for a product that is only approved to treat about 28,000 people worldwide.

Dr. Steven D. Pearson, the president of the Institute for Clinical and Economic Review, which evaluates the cost-effectiveness of drugs, said the problem is that in the United States, drug companies control the prices, especially in the case of newly approved drugs like Orkambi.

“Our system is set up not to distinguish very well between those drugs that are fairly priced and those that are not,” he said. Dr. Pearson’s institute concluded that Vertex’s cystic-fibrosis drugs should be discounted by as much as 77 percent. “That gives the incentive to the company to overreach, and that’s part of why our system is so out of whack,” he said.

In April, Orkambi became the test case for the New York law when a state board ruled that the drug was not worth its cost, recommending that it be discounted from the list price by roughly 70 percent — an amount that was influenced by work done by Dr. Pearson’s institute. New York’s law, passed in 2017, allows the state to ask manufacturers for a deeper discount if the state’s Medicaid drug budget exceeds a certain amount.

Under federal law, state Medicaid programs get a rebate of at least 23 percent. New York officials said that they identified 30 drugs this year that were priced too high, and that those products’ manufacturers agreed to deeper discounts, resulting in about $60 million in annual savings. Vertex, which is based in Boston, was the only company that refused, the state said. New York officials did not identify the manufacturers that agreed to steeper discounts.

For now, at least, Vertex appears to have the upper hand because federal law requires the state to cover Orkambi, although the state can limit its use. Under its new law, New York could also demand that Vertex disclose details about how it sets its price, including how much goes toward research and development or to other areas, like marketing. But even if Vertex complied, that information would not be made public because it is considered proprietary.

Ms. Nichols, the Vertex spokeswoman, said the company had no plans to agree to a discount below the 23 percent required by law.

And Donna Frescatore, the director of New York’s Medicaid program, said she was reluctant to limit the use of Orkambi for those who need it. “It’s certainly a balance with our ability to get fair pricing for this medication,” she said.

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Ms. Moser prepares to administer medication through a nebulizer at her home in Leander, Tex. CreditTamir Kalifa for The New York Times

But despite the impasse, Mr. Salo said big states like New York are major buyers of prescription drugs, and companies may see an interest in taking those states seriously. “I see this as being of very, very widespread interest,” he said. “A lot of other states are kind of watching and saying, ‘How is that going to work?’”

The debate over Orkambi may soon become moot — earlier this year, the Food and Drug Administration approved a new cystic fibrosis drug, also made by Vertex. Symdeko, as the drug is called, treats a similar population as Orkambi, but has been proven to be more effective. It carries a list price of $292,000 a year, and some analysts, including Geoffrey Porges, of Leerink, say they believe Symdeko will eventually replace Orkambi.

Given the arrival of Symdeko, some analysts said New York would be smart to negotiate a package deal for all three of Vertex’s cystic fibrosis drugs, similar to a deal recently made with Ireland. Ms. Frescatore said that’s an approach that she would consider.

“You don’t want a patient being forced to take Orkambi because it’s cheaper,” Mr. Porges said. “You want the right patient to get the right medicine.”

Katie Thomas covers the business of health care, with a focus on the drug industry. She started at The Times in 2008 as a sports reporter. @katie_thomas

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