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.

Advertisement

“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.

Image
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.

Image

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

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

Low Level of Zinc Ions in Lungs Contribute to Buildup of Mucus in CF

When two channels that are supposed to move chloride and sodium ions out of cells in the lungs fail to function properly, it leads to the mucus buildup seen in cystic fibrosis.

Japanese researchers have discovered that the channel dysfunctions also reduce the amount of zinc ions going into the lungs, further contributing to the thick mucus accumulation.

Their study, published in the journal EBioMedicine, is titled “Zinc Deficiency via a Splice Switch in Zinc Importer ZIP2/SLC39A2 Causes Cystic Fibrosis-Associated MUC5AC Hypersecretion in Airway Epithelial Cells.Continue reading Low Level of Zinc Ions in Lungs Contribute to Buildup of Mucus in CF

A Breath of Fresh Air for Biotechs Working on Cystic Fibrosis Therapies

Researchers from the University of Zurich have determined the structure of a chloride channel, which could be a target for new drugs to treat cystic fibrosis.

Researchers at the University of Zurich have found a new target for future cystic fibrosis treatments. The study, published in Nature, has uncovered the structure of a protein that could help to correct the mechanism underlying the buildup of sticky mucus in patients’ lungs. This could give rise to a new wave of therapeutics for the condition, which at the moment lacks disease-modifying treatments.

Cystic fibrosis is a severe genetic disease affecting the lungs, for which there is currently no cure. It is caused by a malfunctioning chloride channel, CFTR, which prevents the secretion of chloride by cells, leading to the production of thick, sticky mucus in the lung. The condition affects around 70,000 people worldwide, who suffer from chronic infections and require daily physiotherapy.

However, one potential approach to treat cystic fibrosis is to activate the calcium-activated chloride channel, TMEM16A, as an alternative route for chloride efflux. As TMEM16A is located within the same epithelium as CFTR, its activation could rehydrate the mucus layer. The research group used cryo-electron microscopy to decipher the structure of TMEM16A, which is part of a protein family that facilitates the flow of negatively charged ions or lipids across the cell membrane.

The changes that occur in the lungs of cystic fibrosis patients.

TMEM16A is found in many of our organs, playing a key role in muscle contraction and pain perception, as well as in the lungs. It forms an hourglass-shaped protein-enclosed channel, which when bound by positively charged calcium ions, opens to let chloride ions to pass through the membrane.

Current treatments for cystic fibrosis include bronchodilators, mucus thinners, antibiotics, and physiotherapy, which only control symptoms. However, biotechs around Europe are beginning to make progress, with ProQR completing a Phase Ib trial and Galapagos and Abbvie’s triple combination therapy entering Phase I. Antabio has also received €7.6M from CARB-X to develop a new antibiotic against Pseudomonas infections.

The identification of a new target provides patients and biotechs alike with renewed hope of new and effective cystic fibrosis treatments, or even a cure. It will be interesting to see whether small molecules or gene therapy specialists could take advantage of this information.

Original article: https://labiotech.eu/cystic-fibrosis-treatment-target/

Cancer gene plays key role in cystic fibrosis lung infections

PTEN is best known as a tumor suppressor, a type of protein that protects cells from growing uncontrollably and becoming cancerous. But according to a new study from Columbia University Medical Center (CUMC), PTEN has a second, previously unknown talent: working with another protein, CFTR, it also keeps lung tissue free and clear of potentially dangerous infections.

The findings, published in Immunity, explain why people with cystic  are particularly prone to respiratory infections—and suggest a new approach to treatment.

A quarter-century ago, researchers discovered that cystic fibrosis is caused by mutations in the CFTR gene, which makes an eponymous protein that transports chloride ions in and out of the cell. Without ion transport, mucus in the lung becomes thicker and stickier and traps bacteria—especially Pseudomonas—in the lung. The trapped bacteria exacerbate the body’s inflammatory response, leading to persistent, debilitating infections.

But newer research suggests CFTR mutations also encourage infections through a completely different manner.

“Recent findings suggested that  with CFTR mutations have a weaker response to bacteria, reducing their ability to clear infections and augmenting inflammation,” said lead author Sebastián A. Riquelme, PhD, a postdoctoral fellow at CUMC. “This was interesting because it pointed to a parallel deregulated immune mechanism that contributes to airway destruction, beyond CFTR’s effect on mucus.”

That’s where PTEN comes into play. “We had no idea that PTEN was involved in cystic fibrosis,” said study leader Alice Prince, MD, professor of pediatrics (in pharmacology). “We were studying mice that lack a form of PTEN and noticed that they had a severe inflammatory response to Pseudomonas and diminished clearance that looked a lot like what we see in patients with cystic fibrosis.”

Delving deeper, the CUMC team discovered that when PTEN is located on the surface of lung and immune cells, it helps clear Pseudomonas bacteria and keeps the inflammatory response in check. But PTEN can do this only when it’s attached to CFTR.

And in most cases of cystic fibrosis, little CFTR finds it way to the cell surface. As a result, the duo fail to connect, and Pseudomonas run wild.

As it happens, the latest generation of cystic fibrosis drugs push mutated CFTR to the cell surface, with the aim of improving chloride channel function and reducing a buildup of mucus. The new findings suggest that it might be beneficial to coax nonfunctional CFTR to the surface as well, since even abnormal CFTR can work with PTEN to fight infections, according to the researchers.

“Another idea is to find drugs that improve PTEN membrane anti-inflammatory activity directly,” said Dr. Riquelme. “There are several PTEN promotors under investigation as cancer treatments that might prove useful in cystic fibrosis.”

The study also raises the possibility that PTEN might have something to do with the increased risk of gastrointestinal cancer in . “With better clinical care, these patients are living much longer, and we’re seeing a rise in gastrointestinal cancers,” said Dr. Prince. “Some studies suggest that CFTR may be a tumor suppressor. Our work offers an alternative hypothesis, where CFTR mutations and lack of its partner, PTEN, might be driving this cancer in patients with .”

The paper is titled, “Cystic fibrosis transmembrane conductance regulator attaches tumor suppressor PTEN to the membrane and promotes anti Pseudomonas aeruginosa immunity.”

For journal article click here:

http://www.cell.com/immunity/fulltext/S1074-7613(17)30487-9

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

FDA Approves Kalydeco for Cystic Fibrosis Patients Ages 2 and Up

http://www.raredr.com/

The U.S. Food and Drug Administration (FDA) continues to provide new indications for Vertex’s Kalydeco (ivacaftor) for Cystic Fibrosis (CF) patients. Earlier today, it was approved for use in more than 600 patients ages 2 and older who have 1 of 5 residual function mutations that results in a splicing Continue reading FDA Approves Kalydeco for Cystic Fibrosis Patients Ages 2 and Up

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

AbbVie, Galapagos’ Kalydeco challenger clears phase 2

http://www.fiercebiotech.com/biotech/abbvie-galapagos-kalydeco-challenger-clears-phase-2
Galapagos has posted phase 2 data on the cystic fibrosis drug it is developing with AbbVie. The data suggest the potentiator can play a role in challenging Vertex’s Kalydeco and its follow-up programs, although its place in a planned triple-combination therapy may be taken by a competing Continue reading AbbVie, Galapagos’ Kalydeco challenger clears phase 2

My Five Takeaways from #NACFC2016

I had a dream last night, and in that dream the Limp Bizkit classic song, Nookie was on repeat for some reason. I have no idea why; I haven’t heard that song in about 12 years. Needless to say I woke up pretty jacked up and motivated to get sh*t done before the Packers game this afternoon. Continue reading My Five Takeaways from #NACFC2016