The Most Important New Drug Of 2012

PHARMA & HEALTHCARE  FIND THIS ARTICLE HERE: http://www.forbes.com/sites/matthewherper/2012/12/27/the-most-important-new-drug-of-2012/

The Food and Drug Administration looks set for a great 2012; with a few days left to go, it has approved 40 new drugs and vaccines, one of the most impressive totals ever, according to data from Pharmaceutical Approvals Monthly and FDA press releases. In this haul, one medicine stands out for its scientific and medical importance.

Kalydeco, for cystic fibrosis, is a triumph of genetics and drug development, the first medicine to directly affect the genetic defect that causes the disease. It will only help 4% of the 70,000 people who suffer from declining lung function, damaged pancreases, and shortened lives due to CF worldwide, but in those few it has a dramatic effect. It makes medical history for three reasons:

·         It’s a genomics triumph: Francis Collins, later famous for heading the Human Genome Project and then the National Institutes of Health, discovered the gene that, when mutated, causes cystic fibrosis 23 years ago. Kalydeco is the first drug to directly affect the defects caused by these mutations, leading to improvements in patients’ lung function.

·         A patient group powered its development:Kalydeco would probably not exist were it not for the Cystic Fibrosis Foundation, which funded its early development at Vertex and gets a royalty on the drug. This success paved the way for other disease foundations including the Michael J. Fox Foundation, Myelin Repair, and the Multiple Myeloma Research Foundation.

·         Its price: Kalydeco, given alone, will only help a few thousand patients the world over. Like other drugs for very rare diseases, its price is very high: $294,000 per patient per year.

Vertex shares have fallen 37% from their high earlier this year because of doubts by investors that Vertex will succeed in its attempts to dramatically expand Kalydeco’s use by combining it with a second drug that will make it work in CF patients whose disease is caused by other, more common, mutations. Initial results were very promising, but then Vertex had to restate them. Sales of its best-seller, Incivek for hepatitis C, are dropping. But whatever you think of Vertex shares, Kalydeco is already a success, with $113 million in sales in the first nine months of 2012.

Kalydeco was not the only important drug this year, in which the FDA also approved the first flu vaccine made in cells, not chicken eggs (that’s a Novartis product) and several important cancer drugs including Onyx’s Kyprolis, Medivation’s Xtandi, and Roche’s Perjeta. Nor is it the most commercially important — that honor goes to Gilead’s Stribild combination pill for HIV, which could help preserve that company’s HIV franchise through patent expirations. But it’s probably the most exciting as a harbinger of drugs to come.

Will Pfizer Challenge Vertex Pharmaceuticals’ Orphan Drug Kalydeco (Ivacaftor) Cystic Fibrosis Empire ?

November 21, 2012

       Pfizer announces on November 19, 2012, that the company is to receive up to $58 million in a 6-year pre-clinical R&D program, from Cystic Fibrosis FoundationTherapeutics (CFFT).  The program is to develop new drugs for the most common mutation of the disease – the Delta F508 mutation. CFFT is the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation (CFF). 

       Almost 90% of CF patients have at least 1 copy of the Delta F508 mutation. This mutation prevents a protein from maintaining the proper flow of salt and fluids into airways, causing thick secretions to form.

      The Cystic Fibrosis (CF) Foundation gave $75 million to Vertex Pharmaceuticals for the “collaboration of scientific, clinical, and financial support for the development of orphan drug Kalydeco (Ivacaftor)”. 

      Vertex Pharmaceuticals reports on November 1, 2012, at their 3^rd Quarter 2012 financial results meeting, the following for their CF Development Programs :  

1)       Three Phase 3 label expansion trials :  

-          Phase 3 study of Kalydeco currently ongoing in patients with CF, 6 years and older, and have at least 1 copy of the R117H mutation – an estimated 3% of US CF patients have at least 1 R117H mutation  

-          Phase 3 study of Kalydeco currently ongoing in patients with CF, 6 years and older, and who have at least 1 non-G551D CFTR gating mutation – an estimated 1% of US CF patients have at least 1 non-G551D gating mutation  

      -  Phase 3 study of Kalydeco recently initiated in children with CF, 2 – 5 years of age, and who have a gating mutation; enrollment to start by end of 2012.  

2)       One Phase 2 study underway for Kalydeco monotherapy :  

     -  Phase 2 proof-of-concept study evaluating Kalydeco in people with clinical evidence of residual CFTR function – an estimated 5 – 10% of US CF people may have residual CFTR function

3)  Study to start at beginning of 2013 to evaluate combination therapy of VX-809 and Kalydeco, in patients with CF, ages 12 and older, and with 2 copies of the F508del mutation – most common form of CF  

4)  To identify additional CF treatment regimens in collaboration with the CF Foundation Therapeutics.  

References 

Cystic Fibrosis Foundation Drug Development Pipeline  

PharmaPhorum.com November 20, 2012 article titled, “Cystic Fibrosis Foundation to invest up to $58m in Pfizer partnership” 

Copyright © 2012-2013, Orphan Druganaut Blog.  All rights reserved.

Drug Fulfills Promise Of Research Into Cystic Fibrosis Gene

Find the story and podcast here: http://www.npr.org/blogs/health/2013/01/02/168353348/drug-fulfills-promise-of-research-into-cystic-fibrosis-gene

by JOE PALCA

January 02, 2013 3:04 PM

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All Things Considered

4 min 24 sec

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Jeffrey Sauger

The promise of genetic medicine is beginning to be fulfilled, but it's been a long, hard slog.

Take the story of Kalydeco. It's designed to treat people with a lung disease called cystic fibrosis. While not quite a cure, the drug is extremely effective for some CF patients.

But the success of Kalydeco has been more than two decades in the making.

A good starting point for the story is Aug. 24, 1989. That's the day scientists from the U.S. and Canada announced the discovery of the gene associated with the disease. It was the early days of gene hunting, and the CF gene was a big prize.

CF is the most common genetic disease in Caucasians. When people inherit a damaged form of the CF gene, a critical protein inside cells doesn't work properly. As a result, sticky mucus builds up in a patient's lungs, causing infections and making it hard to breathe.

The announcement was supposed to be made in conjunction with three papers in the Sept. 8 issue of Science, but a reporter for Reuters got hold of the story early. Science took the unusual step of allowing the scientists to speak to the media before publication.

At the time, scientists predicted that a genetic test for CF was just around the corner. But they also thought a drug to treat the disease was in reach.

The first prediction turned out to be right. "But it wasn't until 20 years later that we were able to find drugs that directly target the underlying cause of cystic fibrosis," says Fred Van Goor, who led the team at what is now Vertex Pharmaceuticals that developed Kalydeco. "So it was a long time between the discovery of the gene and the discovery of Kalyedco."

Kalydeco is one of the first drugs that is effective at combating the root causes of a genetic disease.

Vertex Pharmaceuticals Inc.

It took awhile to find a drug that would help restore the function of the protein the CF gene makes. "We tested over 600,000 chemicals in cells with the defective protein that causes cystic fibrosis," says Van Goor.

One of those chemicals ultimately became a successful drug, but it had to be modified so patients could take it by mouth, and so it would last the right length of time in a patient's body.

From the start, Van Goor and his colleagues knew there was a problem with Kalydeco: It only works on a small subset of people with CF. They have to have a particular mutation in the CF gene, or the drug is of little use.

But for people who do have that mutation, the drug works remarkably well.

Emily Schaller was in one of the early studies of Kalydeco. As part of the study, researchers first gave her a placebo, then switched her to the active drug. She knew within days that something was different.

"I was with my brother in Florida, and we were walking down the street, and I took a deep breath, and when I took a deep breath in and I let it out, I didn't cough," says Schaller. "But not only did I not cough, but I felt that my lungs were clear, and that something huge had happened. It was just something I had never felt in my life before."

Schaller isn't cured. She still has a damaged CF gene. The only way to fix that would be gene therapy, where a healthy form of the gene would supplant the damaged one. Although it seems simple in theory, in practice gene therapy has been incredibly difficult to accomplish.

Schaller isn't particularly bothered by that. "Everyone talks about curing a disease — cure CF, cure these other diseases. [But] Kalydeco controls CF at the basic defect, so I'm OK with the other 'c' word, control, because I'm living it and I've never felt better in my life."

The time from gene discovery to successful drug may be shortening, but there are only a handful of successful drugs so far, and for a while at least, the appearance of new ones will be slow.

They're also likely to be expensive. Kalydeco costs in the neighborhood of $300,000 per year.