Kalydeco, Drug That Treats Root Cause Of Cystic Fibrosis, Approved By FDA

WASHINGTON — The first drug that treats the root cause of cystic fibrosis won approval Tuesday, offering a life-changing treatment for a handful of patients with the deadly illness and broader hope for thousands more patients with the inherited disease.

About 30,000 Americans live with cystic fibrosis, a disease that causes sticky mucus buildup in the lungs and other organs, leading to infections, digestive problems and death in young adulthood. The typical life expectancy is about 37 years, according to the Cystic Fibrosis Foundation.

The Food and Drug Administration approved Vertex Pharmaceuticals Inc.'s Kalydeco for patients with a rare form of the disease that affects just 1,200 people in the U.S., about 4 percent of affected population nationwide. These patients have a protein defect that prevents their cells from properly absorbing and excreting salt and water. Studies of the drug showed it significantly improved lung function and reduced other symptoms of cystic fibrosis.

"Even though this drug isn't for the majority of people, it proves that you can look at the mistake in the genes and design a drug in a rational way that will fix the problem," said Dr. Drucy Borowitz of the State University of New York at Buffalo, where she directs the cystic fibrosis program.

The twice-a-day pill is among the first drugs designed to a correct a specific genetic defect. Its development characterizes both the promise and challenges of that approach. Scientists first identified the gene that causes cystic fibrosis in 1989, but it took more than two decades and more than $75 million in outside funding to develop a drug to treat the disease.

Borowitz enrolled several of her patients in the key study for Kalydeco, which showed that patients taking the drug increased their lung strength more than 10 percent when compared with patients taking a placebo. Patients also had fewer infections and gained nearly seven pounds on average, a significant amount for patients who typically have trouble retaining weight. All patients in the study continued taking older medications that help loosen mucus.

"Two weeks after using the drug my lung tests were above average for a healthy 15-year-old who didn't have cystic fibrosis," said Nick Mangano, 17, a Borowitz patient who has been taking the drug for two years. Before starting on Kalydeco, Mangano said he was hospitalized for lung infections five times in four years. Now he says he usually recovers from a cold within a week or two.

"I don't really need medicine for it anymore, it's totally different," said Mangano, who is considering leaving Buffalo for college next year – a step he hadn't previously considered because of his dependence on his family and physicians.

Only a few decades ago, children with cystic fibrosis seldom survived elementary school. Today, thanks to earlier diagnosis and new focus on diet and physical therapy, 47 percent live to be 18 or older.

The FDA approved the drug for patients 6 years old and up, though Vertex is also planning to study the drug in patients as young as 2 years old. Researchers hope that by using the drug earlier they will be able to prevent permanent lung damage, which is the primary cause of death for cystic fibrosis patients.

Mangano and others with the so-called G551D mutation have a defective protein that fails to balance the flow of chloride and water across the cell wall, leading to the buildup of internal mucus. The vast majority of cystic fibrosis patients have a different genetic defect, in which the protein does not reach the cell wall. Vertex is developing another drug to try and address that problem. Study data for that drug is expected later this year.

Kalydeco is part of a growing number of new medicines that target rare genetic variations found in subgroups of patients. Last year Pfizer launched a new lung cancer drug called Xalkori, which targets cancer linked to a genetic mutation found in less than 7 percent of patients.

Vertex executives said Kalydeco would cost $294,000 for a year's supply, placing it among the most expensive prescription drugs sold in the U.S. Specialty drugmakers are known to charge $300,000 or more for drugs that treat very small groups of patients.

"The drug is priced for the value it will deliver to this very small group of patients," Vertex Executive Vice President Nancy Wysenski told analysts.

Wysenski said Vertex would provide the medicine for free to people with no insurance and household income of $150,000 or less. The company will also cover 30 percent of copay costs for select patients who have insurance.

The FDA approved the drug in approximately three months, half the time usually needed for high-priority drugs.

After scientists identified the genetic sequence that causes cystic fibrosis in 1989, many experts hoped the disease could be cured by replacing the gene with a normal one. However, attempts at so-called gene therapy proved unsuccessful, and researchers began looking for ways to correct the genetic defect.

"I think it took the field about a decade to realize we had to look for other options," said Paul Negulescu, vice president of research at Vertex Pharmaceuticals.

In 1998, the Cystic Fibrosis Foundation approached Aurora BioSciences, now part of Vertex, to help screen potential drug candidates for a cystic fibrosis drug. In 2000, the foundation awarded the company more than $45 million to study and commercialize an experimental drug for the disease, the largest grant of its kind by a nonprofit disease group. To date, Vertex has received over $75 million in research and development funding from the Cystic Fibrosis Foundation. Vertex said it also spent hundreds of millions of dollars of its own money, though it did not specify the exact amount.

Cambridge, Mass.-based Vertex has only one other drug on the market, the hepatitis C drug Incivek, which launched last May.

Company shares rose $2.21, or 6.4 percent, to $36.95 in trading Tuesday.

The most common side effects with Kalydeco include headache, stomach ache, rash diarrhea and dizziness.

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Comments

[musichelpslots]

02:46 PM on 01/31/2012

$75 million to develop, over 20 years, for 1,200 patients = $62,500. So $294,000 per year, per patient is a very nice profit.

[yessiryes]

04:13 PM on 01/31/2012

$75 million was funding from the CFF, Vertex spent hundreds of millions more of its own money on the project

[Head FullaBooks]

06:02 PM on 01/31/2012

I'll give you credit for being able to do basic math, but you need to sharpen your reading comprehension because you forgot to add into your equation that: "Vertex said it also spent hundreds of millions of dollars of its own money, though it did not specify the exact amount."
Not to mention no statement was made about production costs.

Plus Vertex will eat the entire cost in some patient's cases and also help to compensate in others:

"...Vertex would provide the medicine for free to people with no insurance and household income of $150,000 or less. The company will also cover 30 percent of copay costs for select patients who have insurance."

Considering the median income for family of 4 in the US is only around $70k, I'm guessing that the cost of treatment for a significant portion of those 1,200 patients will be entirely covered by Vertex.

Try and give them little credit for producing a groundbreaking drug that will allow a group of people with a catastrophic illness the ability to literally breathe easier and live longer, healthier lives, while also taking into consideration that a great deal of the profit they DO make will most likely be funneled back into more research for more drugs, hmm?

[mgarrison0827]

06:34 AM on 02/01/2012

I will not give them any credit. They have known the root gene that causes CF for almost 20 years. They have had these drugs for years, but the FDA sits on their hands and stalls every approval of drugs that might actually save people's lives. My cousin died of CF at the age of 22 because of this. My aunt was so grieved thatbshe went into a deep depression for years that may or may not have led to her early death. in August of 2010. And they are only approving drugs for the smallest population of victims of tis horrible disease? What about the thousands of others with the most common genetic strains of CF? Yes, I am gladmfor the lives that will be improved over this, but I hardly think the results the FDA have provided match the money they have made on this research!

[running with turtles]

01:47 PM on 01/31/2012

VA Jill,

Vertex has announced they will cover the cost of medication for families making less than $150,000 a year who do not have health insurance.

In addition, since the disease is categorized as an "orphan disease", the government will heavily subsidize it.

This is such an important break-through for patients. I have met with patients who have been on the clinical trial for this drug and their improvement is nothing short of life-changing. It makes one emotional, really.

[mgarrison0827]

06:37 AM on 02/01/2012

Orphan disease? This was the most common genetic disease for decades! My cousin died of this horrible disease and he suffered almost every day of his life. I have no respect for the FDA when the have had the research to cure this diseas for almost 20 yeras and are just now rleasing meds to help only the smallest population suffering this horrible fate.

[Head FullaBooks]

11:15 AM on 02/01/2012

This particular variant of CF is considered an orphan disease, not CF in general. I'm very sorry you lost a loved one to CF. I have no personal connection with this CF but my aunt and father were crippled by polio as children, I've lost family members to cancer, have a very young cousin with severe diabetes and have seen my grandmother become a shell of herself from the ravages of Alzheimers. I'd say its a good guess that more than a few researchers and even those money grubbing pharmaceutical company and FDA employees have themselves suffered or watched a family member suffer from such diseases and have every reason to want to find and produce life saving cures ASAP.

The hard, sad fact is that very little is straight forward when it comes to human biology and medicine and to do proper research requires lots of time and lots of money. When Vertex realized that this research would only be immediately applicable to a very small percentage of people, they could have tossed it aside and focused solely on something bigger and flashier but they didn't. They helped the people that could be helped ASAP while continuing to seek how they can help more. I say Bravo.

[synergie]

01:21 AM on 02/02/2012

This is a breakthrough and those 20 years were spent getting to this point, no one was holding out on you. I'm sorry that your cousin suffered, but that doesn't mean that the FDA is to blame.

They still don't have a cure for this disease. They were just able to figure out how to correct the flaw caused by a rare version of a genetic defect that causes this disease in a very small group of people, thus making it an "orphan disease". You see, the hit on a drug that helped the rare variation, which they were not trying to address while they looked for ways to treat the most common genetic mutation that your cousin most likely suffered from. I guess you must have someone to blame for the accident of genetics in your family's genetic history, but constructing paranoid fiction about the FDA isn't really conducive to anything.

[VA Jill]

01:00 PM on 01/31/2012

Of course the price will make it out of reach for a lot of families, and the insurance companies will balk at paying.....

[yessiryes]

04:11 PM on 01/31/2012

"Wysenski said Vertex would provide the medicine for free to people with no insurance and household income of $150,000 or less. The company will also cover 30 percent of copay costs for select patients who have insurance."

Also, compared to the costs of a lifetime of other medicines and frequent hospital stays, I'm sure insurance companies would rather pay for kalydeco.

[VA Jill]

06:25 PM on 01/31/2012

Obviously you have never had to deal with insurance case management. Things that would seem to make perfect sense to everyone else are just "not allowed". Six years of dealing with that insanity was enough.

[mgarrison0827]

06:43 AM on 02/01/2012

Yes, they can afford to give it for free when they are only helping the smallest portion of patients actually suffering this disease. The money the FDA has gotten has far outweighed the results on the research they have had to cure thisndisease for decades. For 20 years they have known the genetic cause of CF and they are only now helping the smallest few. Granted, people live longer than they used to with CF, but much more could have and should have been done before now. My cousin died at 22 of this disease, so I know what people suffer with CF. They knew enough to help people like him then, but held off on releasing drug trials. So I see this as only a limited victory for these precious young victims of CF.

[onionboy]

12:23 PM on 01/31/2012

Wow. A well-orchestrated R&D process. And kudos to the CFF for showing what dedicated advocacy can accomplish.

[mgarrison0827]

06:57 AM on 02/01/2012

I have nothing but respect for the CFF. Wonderful organization, but the R&D process was not what you think. The FDA stalled for years on clinical trials that would have helped these patients. they have known the genetic cause for decades and are just now helping the smallest population with CF. I call this bittersweet at best, especially for people like my cousin, who died at 22 from this disease. He prayed for a cure every day of his life. His hopes were high when they found the cause, but it never came. As far as I'm concerned, the money they have made ofr the research has far outweighed the results on this horrible disease!

[onionboy]

12:32 PM on 02/01/2012

With regard to R&D, I was more referring to going after the culprit faulty protein rather than coming up with a therapy to solely treat the exhibited symptomology.

Your point on the regulatory hurdles with the FDA, however, is well taken. I'm sorry about your cousin.

[synergie]

01:27 AM on 02/02/2012

Identifying the gene responsible and finding out exactly how to fix what it messes up are two very different things.

Who exactly has made money off the research?