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.

To read original article click here.

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/

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

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

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

Vertex Drug Gets Priority Review for Cystic Fibrosis

http://www.empr.com/drugs-in-the-pipeline/tezacaftor-ivacaftor-vertex-cystic-fibrosis-priority-review-nda/article/684284/

Tezacaftor/Ivacaftor Gets Priority Review for Cystic Fibrosis

The Food and Drug Administration (FDA) has granted Priority Review to the New Drug Application (NDA) of tezacaftor/ivacaftor (Vertex) for the treatment of patients ≥12yrs old with cystic fibrosis (CF) who have two copies of the F508del mutation or one F508del mutation and one residual function mutation.

The NDA submission was based on positive results from 2 global Phase 3 trials, which showed statistically significant improvements in lung function (percent predicted forced expiratory volume in one second, or ppFEV1) in patients treated with tezacaftor/ivacaftor.

The combination treatment consists of ivacaftor (marketed under the brand name Kalydeco), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, and tezacaftor, a novel CFTR corrector. Tezacaftor is designed to address the processing defect of F508del-CFTR to enable it to reach the cell surface, where ivacaftor can further enhance the protein’s function.

The FDA has set a Prescription Drug User Fee Act (PDUFA) target date of February 28, 2018 to make a decision on the NDA.

For more information visit Vrtx.com.

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

Clinical and Regulatory Progress Across Pipeline Programs for Drug Company

http://www.nasdaq.com/press-release/proteostasis-therapeutics-announces-clinical-and-regulatory-progress-across-pipeline-programs-20170607-00270

Proteostasis Therapeutics Announces Clinical and Regulatory Progress Across Pipeline Programs

Updates Announced During the 40th European Cystic Fibrosis Society Conference

Proteostasis Therapeutics, Inc. (NASDAQ:PTI), a biopharmaceutical company developing small molecule therapeutics to treat diseases caused by Continue reading Clinical and Regulatory Progress Across Pipeline Programs for Drug Company