CF Worldwide Blog

CAMBRIDGE, Mass.–(BUSINESS WIRE)–      Vertex Pharmaceuticals Incorporated(Nasdaq: VRTX) today announced data      from a Phase 2 study of VX-661 and ivacaftor that showed statistically      significant improvements in lung function among adults with cystic      fibrosis (CF) who have two copies (homozygous) of the most common      mutation in the cystic fibrosis transmembrane conductance regulator (CFTR)      gene, known as F508del. The study evaluated four dose levels of VX-661      (10, 30, 100 and 150 mg) dosed once daily for 28 days in combination      with ivacaftor (150 mg) dosed twice daily. The study also evaluated a      separate group of patients who received VX-661 (10, 30, 100 and 150 mg)      dosed without ivacaftor for 28 days. Dose-dependent, mean relative      improvements in lung function (percent predicted forced expiratory      volume in one second; FEV₁), both within group and versus      placebo, were observed across the combination dosing groups. Patients in      the 100 and 150 mg combination dose groups showed statistically      significant mean relative improvements in lung function, versus placebo,      of 9.0 percent (p=0.01) and 7.5 percent (p=0.02), respectively, at Day      28. In contrast, patients who received placebo showed a 0.03 percent      mean relative change in lung function at Day 28 (within-group). The mean      relative FEV₁ across the combination dose groups returned      toward baseline during the post-treatment 28-day washout period. VX-661      was generally well-tolerated, both as monotherapy and in combination      with ivacaftor, and most adverse events were mild to moderate in      severity and similar between the treatment groups and those who received      placebo. Vertex plans to conduct additional studies of VX-661 to further      evaluate its potential for late-stage development, pending regulatory      discussions.

“This first study of VX-661 and ivacaftor provides further validation of      the strategy of combining a corrector and potentiator to improve lung      function in people with the most common type of cystic fibrosis,”Peter      Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of     Global Researchand Development at Vertex. “With these data and the      recent initiation of a Phase 3 program for a combination of our lead      CFTR corrector VX-809 with ivacaftor, we are making significant progress      toward our goal to help many more people with CF.”

Cystic fibrosis is caused by a defective or missing CFTR protein      resulting from mutations in the CFTR gene. In people with two      copies of the most common mutation in the CFTR gene, F508del,      little to no CFTR protein reaches the cell surface. VX-661, known as a      CFTR corrector, is believed to help CFTR protein reach the cell surface.      Ivacaftor, known as a CFTR potentiator, keeps cell surface CFTR protein      channels open longer to increase the flow of salt and water. Worldwide,      nearly half of people with CF have two copies of the F508del mutation      and an additional one-third have one copy of the F508del mutation.

About the Study

The Phase 2 randomized, double-blind, placebo-controlled study treated      128 people with CF ages 18 and older with two copies of the F508del      mutation. One group of patients was randomized to receive either VX-661      (10, 30, 100 and 150 mg dosed once daily), or placebo, alone for 28      days. A separate group of patients was randomized to receive the      combination of VX-661 (10, 30, 100 and 150 mg dosed once daily) and      ivacaftor (150 mg dosed twice daily), or placebo, for 28 days. The      primary endpoints of the study were safety, tolerability and change in      sweat chloride. Change in lung function (percent predicted forced      expiratory volume in one second; FEV₁) was measured as a      secondary endpoint.

There were statistically significant mean absolute decreases in sweat      chloride, both within-group and versus placebo, across the combination      and monotherapy groups. These changes were generally modest and were      variable across the dose groups.

VX-661 was generally well-tolerated when dosed alone and in combination      with ivacaftor. The most common adverse events were pulmonary in nature.      Most adverse events were mild to moderate in severity and similar      between the treatment and placebo groups, and the types and frequency of      adverse events were similar between the treatment and placebo groups.      The rate of serious adverse events was also similar between the      treatment groups and those who received placebo.

Lung Function Results for Combination Dosing

Mean absolute and relative improvements in lung function were observed      in all the combination dosing groups (10, 30, 100 and 150 mg), both      within group and versus placebo. The improvements in lung function were      dose dependent, with the greatest improvements observed in the groups      that received the highest doses of VX-661 in combination with ivacaftor.      Patients in the two highest combination dose groups (VX-661 100 mg or      150 mg in combination with ivacaftor 150 mg) showed statistically      significant mean relative improvements in lung function, versus placebo,      of 9.0 percent (p=0.01) and 7.5 percent (p=0.02), respectively at Day      28. Improvements in FEV₁ were observed early in treatment,      and the mean relative FEV₁ improvements, versus placebo, for      the highest combination group (VX-661 150 mg in combination with      ivacaftor 150 mg) were statistically significant at Days 14, 21 and 28.      The mean relative FEV₁ across the combination dose groups      returned toward baseline during the post-treatment 28-day washout      period. Additional lung function results are noted below:

NS = Not Statistically Significant * The statistical analysis plan      (SAP) for this study did not include statistical comparisons for the      28-day washout period

In the dose group that evaluated 100 mg of VX-661 in combination with      ivacaftor, 66.7 percent (10/15) of patients had a 5 percent or greater      relative improvement (within subject) in lung function at Day 28. In the      dose group that evaluated 150 mg of VX-661 in combination with      ivacaftor, 56.3 percent (9/16) of patients had a 5 percent or greater      relative improvement (within subject) in lung function at Day 28. 21.7      percent (5/23) of patients who received placebo had a 5 percent or      greater relative improvement (within subject) in lung function at Day 28.

Results for VX-661 Monotherapy Dosing

Mean absolute and relative increases in lung function were observed in      all the VX-661 monotherapy dosing groups (10, 30, 100 and 150 mg), both      within group and versus placebo at Day 28. These increases were      variable, not dose-dependent and not statistically significant in any of      the monotherapy dosing groups.

NS = Not Statistically Significant

Advancing Multiple Correctors

Vertex has advanced three correctors from research into development -      VX-809, VX-661 and VX-983. VX-809 is Vertex’s lead corrector and is      currently being evaluated in combination with ivacaftor as part of two      ongoing Phase 3 studies expected to enroll a total of approximately      1,000 people ages 12 and older with two copies of the F508del mutation.      Vertex expects to obtain 24-week safety and efficacy data from these      studies and to submit a New Drug Application (NDA) to the U.S. Food and      Drug Administration(FDA) in 2014, pending study results. VX-661 is      Vertex’s second corrector to enter clinical development. Vertex plans to      conduct additional studies of VX-661 to further evaluate its potential      for late-stage development, pending regulatory discussions. VX-983 is      the third corrector to enter clinical development and is currently being      evaluated as part of a Phase 1 multiple-ascending-dose study in healthy      volunteers. In the second half of 2013, Vertex plans to begin a 28-day      study of VX-983 in combination with ivacaftor in people with two copies      of the F508del CFTR mutation.

In addition to Vertex’s development activities focused on combinations      of a corrector with ivacaftor, the company has an active research      program that has identified next-generation correctors that could be      used as part of future combination regimens for people with CF.

About Cystic Fibrosis

Cystic fibrosis is a rare life-shortening genetic disease for which      there is no cure. It affects approximately 30,000 people inthe United      Statesand 70,000 people worldwide. Today, the median predicted age of      survival for a person with CF is approximately 37 years inthe United      States, but the average age of death remains in the mid-20s.

CF is caused by a defective or missing CFTR protein resulting from      mutations in the CFTR gene. Children must inherit two defective CFTR      genes — one from each parent — to have CF. There are more than 1,800      known mutations in the CFTR gene. Some of these mutations, which      can be determined by a genetic, or genotyping test, lead to CF by      creating non-working or too few CFTR proteins at the cell surface. The      absence of working CFTR proteins results in poor flow of salt and water      into and out of the cell in a number of organs, including the lungs.

Collaborative History with Cystic Fibrosis Foundation Therapeutics,      Inc. (CFFT)

Vertex initiated its CF research program in 1998 as part of a      collaboration with CFFT, the non-profit drug discovery and development      affiliate of theCystic Fibrosis Foundationin the U.S. This      collaboration was expanded to support the accelerated discovery and      development of Vertex’s CFTR modulators.

About Vertex

Vertex creates new possibilities in medicine. Our team discovers,      develops and commercializes innovative therapies so people with serious      diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to      cure or significantly advance the treatment of hepatitis C, cystic      fibrosis, rheumatoid arthritis and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, Mass., we now have ongoing      worldwide research programs and sites in the U.S., U.K.and Canada.      Today, Vertex has more than 2,000 employees around the world, and for      three years in a row, Science magazine has named Vertex one of      its Top Employers in the life sciences.

Conference Call Information

Vertex will host a conference call and webcast today, April 18, 2013at      4:30 p.m. ETto review the Phase 2 results for VX-661. The conference      call will be webcast live, and a link to the webcast may be accessed      from the ‘Vertex Events’ page of Vertex’s website at www.vrtx.com.

To listen to the live call on the telephone, dial 1-866-501-1537 (United      StatesandCanada) or 1-720-545-0001 (International). To ensure a timely      connection, it is recommended that users register at least 15 minutes      prior to the scheduled webcast.

The conference ID number for the live call and replay is 46110587.

The call will be available for replay via telephone commencingApril 18,      2013at8:00 p.m. ETrunning through4:30 p.m. ETonApril 25, 2013. The      replay phone number forthe United StatesandCanadais 1-855-859-2056.      The international replay number is 1-404-537-3406.

Following the live webcast, an archived version will be available on      Vertex’s website until 4:30 p.m. ETon April 25, 2013. Vertex is also      providing a podcast MP3 file available for download on the Vertex      website at www.vrtx.com.

Special Note Regarding Forward-Looking Statements This press      release contains forward-looking statements as defined in the Private      Securities Litigation Reform Act of 1995, including, without limitation,      Dr. Mueller’s statements in the second paragraph of this press release      and statements regarding (i) Vertex’s plans to conduct additional      studies of VX-661 to further evaluate its potential for late-stage      development; (ii) Vertex’s expectation that it will obtain 24-week      safety and efficacy data from its Phase 3 studies of VX-809 in      combination with ivacaftor and submit an NDA to the FDA in 2014, (iii)      Vertex’s plans to begin a 28-day study of VX-983 in combination with      ivacator in the second half of 2013 and (iv) the possibility that      next-generation correctors that Vertex has identified could be used as      part of future combination regimens for people with CF. While Vertex      believes the forward-looking statements contained in this press release      are accurate, those statements are subject to risks and uncertainties      that could cause actual outcomes to vary materially from the outcomes      referenced in the forward-looking statements. These risks and      uncertainties include, among other things: the Phase 3 studies of VX-809      in combination with ivacaftor and the additional studies of VX-661 in      combination with ivacaftor may be prevented or delayed; the Phase 3      studies of VX-809 in combination with ivacaftor may not support      registration and the additional studies of VX-661 in combination with      ivacaftor may not support late-stage development due to safety, efficacy      or other reasons; and the other risks listed under Risk Factors in      Vertex’s annual report and quarterly reports filed with the Securities      and Exchange Commission and available through the company’s website at www.vrtx.com.      Vertex disclaims any obligation to update the information contained in      this press release as new information becomes available.

Cystic fibrosis sufferer Bianca Nicholas has always loved singing – but it was only recently that the 24-year-old realised that her hobby could also potentially change her life, allowing her to manage the debilitating condition herself.

Generally CF sufferers live on a cocktail of drugs and undergo daily physiotherapy to enable them to live as normal a life as possible, due to the build up of mucous that gathers, causing problems including chest infections.

But belting out show tunes is of Bianca’s favourite pastimes and it’s actually helped her to increase her lung capacity to record levels.

“I’ve always sung as a little girl but I got really into it when I joined secondary school and I discovered the more I sang [the better it got].

“The bigger the songs I sang, especially the show tunes, mean I have to take such deep breaths and a lot of the physiotherapy techniques these days are about breathing. It’s just about exercising my lungs and keeping them strong.”

Bianca added: “Because I recently released my single I’ve been doing a lot more singing recently. I had my check up yesterday and my lung function has gone up about 10 per cent and it’s now 93 per cent.”

The outcome has surprised a number of people, who now have new hope that singing could be a therapy that could help many suffers of CF to lead a more normal life.

“I hope I can show other people with CF you can follow your dreams even though you have this condition and not to let it define you,” Bianca explained.

With a single released, two performances for Prince William under her belt, and fans including Paris Hilton, it looks like Bianca’s amazing singing career is going to go from strength-to-strength.

http://entertainment.stv.tv/tv/221793-i-manage-cystic-fibrosis-by-singing-one-womans-inspirational-story/

Pharmaceutical company Pharmaxis (ASX:PXS) is pleased to announce that it has appointed United

Medical Ltda as exclusive distributor and sales representative for Bronchitol® in Brazil.

Under the terms of the agreement United Medical has responsibility for sales and marketing, pricing,

warehousing, distribution and patient support. United will shortly file a marketing approval application

with the Brazilian regulatory agency (ANVISA) based on Bronchitol’s Australian approval, a process which

is expected to take up to 18 months. Pharmaxis will receive milestone payments ahead of Bronchitol’s

approval in Brazil.

United Medical is a well

‐established healthcare company based in São Paulo. It partners with leading

global pharmaceutical companies and its sales team has worked closely with the cystic fibrosis medical

community in Brazil since 1999.

Pharmaxis CEO Mr Gary Phillips said, “This is an important step forward in our plans to commercialise

Bronchitol wherever there are significant markets. Brazil has an estimated 3,500 cystic fibrosis patients

with 32 specialist treatment centres and a well funded reimbursement scheme providing access to new

medications. It is pleasing to have secured the support of an organisation with United Medical’s

experience and track record. Pharmaxis has aligned with a distributor early in the process ensuring we are

well resourced to bring Bronchitol to cystic fibrosis patients in Brazil.”

United Medical has a suite of products associated with the cystic fibrosis market including an inhaled

antibiotic, specific pancreatic enzymes and vitamins.

United Medical CEO Mr Roberto L Guttmann said “We believe Bronchitol is an important tool for

physicians, being at the same time a simple innovative and well rounded solution to achieve a better

quality of life for cystic fibrosis patients. It is an honor for United Medical to make it available here. The

Bronchitol distribution agreement with Pharmaxis allows us to build on our strong relationships with the

cystic fibrosis community in Brazil.”

Bronchitol® is a precision spray

‐dried form of mannitol, delivered to the lungs by a specially designed,

portable inhaler. The product is approved for marketing for patients aged over six years in Australia and

for patients aged 18 years and over throughout the European Union.

#ENDS#

SOURCE:

Pharmaxis Ltd, Sydney, Australia

CONTACT:
Felicity Moffatt, phone +61 418 677 701 or email felicity.moffatt@pharmaxis.com.au

Michael Hughes, 30, from Kingsland in Holyhead, has battled with the disease since birth.

Specialists treating him at Ysbyty Gwynedd and Broadgreen cardiothoracic centre in Liverpool say he is an ideal candidate to use new “wonder drug” Kalydeco (also called Ivacaftor) which has been used elsewhere in Britain since January.

The Welsh Government says the drug is still being appraised by the All Wales Medicines Strategy Group (AWMSG) and a decision on prescribing it here will not be made until May 8.

The drug has been described by the Cystic Fibrosis Foundation as a “cure” for those with the “Celtic” G55ID gene who can use the drug.

Michael’s partner Rachel Roberts, 22, said: “He has this specific gene that means he’s eligible for the drug.

“There are only a handful of CF sufferers in Wales, perhaps half a dozen, that could benefit from using this drug that could radically transform his life.

“Specialists who deal with him have said that he’s an ideal candidate but because of his postcode, living here in Holyhead, he doesn’t qualify.

“It does cost a lot, £182, 000 a year and the trial would cost £1,800, but it seems unfair that Michael is losing out because he lives in Wales.

“Michael is in hospital at the moment. The wait for this drug is weighing heavily on him.”

Rachel went on to add that SSAFA (armed forces charity) on Anglesey had said they would do a charity row to raise money to fund a trial period with the drug, to see what affect it would have for him,

Ed Owen, the Cystic Fibrosis Trust’s  chief executive has been in touch with the Wales Government’s health department.

He said: “We are very concerned that because the AWMSG is not expected to come to a decision on funding until May, Welsh patients face a wait of at least four months at a time when the drug is freely available within the NHS England. This situation is causing considerable heartache and agony for families affected in Wales.

“As the organisation representing people with cystic fibrosis across the UK, the Trust would be appalled at a situation where people in Wales were denied a potentially life-changing treatment freely available in England and Scotland.

“We have campaigned for Kalydeco to be made available across the UK to all those who would benefit from it, and has urged the manufacturer, Vertex, to provide it at a fair and affordable price to the NHS.”

A Wales Government spokeswoman said: “In determining the effectiveness of medicines such as Ivacaftor and their potential benefit to patients, the Welsh Government is guided by the recommendations of the National Institute for Health and Clinical Excellence (NICE) and the All Wales Medicines Strategy Group (AWMSG).

“In the case of Kalydeco/Ivacaftor, the appraisal process is underway and AWMSG are scheduled to make a decision on this new medicine on May 8. If recommended for use, it will be available to patients in Wales.”

http://www.dailypost.co.uk/news/north-wales-news/2013/03/28/cystic-fibrosis-sufferer-facing-long-wait-for-drugs-because-he-lives-in-wales-55578-33076693/

MU Discovery Could Increase Efficacy of Promising Cystic Fibrosis Drug

Data about defective regulatory protein described in Proceedings of the National Academy of Sciences

A little more than a year after the FDA approved Kalydeco (Vx-770), the first drug of its kind to treat the underlying cause of cystic fibrosis, University of Missouri researchers believe they have found exactly how this drug works and how to improve its effectiveness in the future. Described in the current issue of the Proceedings of the National Academy of Sciences, MU researchers have redefined a key regulatory process in the defective protein responsible for cystic fibrosis that could change the way scientists approach the lethal genetic disease.

“They know the drug works, but they don’t know how it works or where it works,” said Tzyh-Chang Hwang, PhD, PNAS corresponding author and professor of medical pharmacology and physiology at the MU School of Medicine. “Our paper provides a theory for how Vx-770 works, and based on our understanding of how the CFTR channel works, we have identified a novel strategy for future explorations to complement and enhance the performance of the existing drug.”

Cystic fibrosis is the second most common life-shortening inherited disorder occurring in childhood in the United States, after sickle cell anemia. Approximately 30,000 Americans have cystic fibrosis, and there are an estimated 1,000 new cases diagnosed each year. Cystic fibrosis patients are born with a genetic defect that causes a malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a chloride channel in the cell membrane that plays a critical role in maintaining water and salt balance across many body tissues, such as sweat glands, tissues that line the lungs, liver, pancreas and reproductive organs.

“The chloride channel is like a pipe that allows ions to travel through at a very fast pace,” Hwang said. “In cystic fibrosis patients the channel is dysfunctional and activity is diminished. So what is the mechanism that controls the opening and closing of the channel? That is the fundamental discovery of our recent papers summarized in Physiology.”

Like an automatic water faucet with a defective hand sensor, many genetic mutations found in cystic fibrosis patients cause a faulty signal, resulting in limited chloride transport across the CFTR. The result is the formation of thick mucus that builds up in the lungs, digestive tract and other parts of the body, which leads to severe respiratory and digestive problems, as well as infections and diabetes.

As summarized in Physiology and followed up with further research in the PNAS article, the accidental discovery of a mutation in CFTR, the R532 mutation, allowed MU researchers to reveal a new “non-strict coupling” relationship that occurs between the consumption of ATP, a molecule that provides energy in the body, and the opening and closing of the CFTR. They argue that the new information uncovered about this mechanism that controls the opening and closing of the CFTR and the passage of ions through it could explain how and where the new cystic fibrosis treatment Kalydeco (Vx-770) works.

“To his credit, Dr. Hwang exploited the behavior of the CFTR mutants to demonstrate that CFTR’s gate is not strictly coupled to the nucleotide binding engine (NBD) that binds and splits ATP [energy] to drive conformational changes that regulate chloride flow through the CFTR protein channel,” said colleague David Sheppard, PhD, an associate professor in the School of Physiology and Pharmacology at the University of Bristol in Bristol, U.K. who did not participate in the study.

In their study, MU researchers were able to observe the effects of the cystic fibrosis drug Vx-770 on the recently discovered R352 mutation. They found that Vx-770 enhances the activity of the CFTR channel by exploiting this “non-coupling” mechanism, a conclusion also supported by experimental results with the wild-type CFTR protein.

“Traditionally, researchers have defined how energy is utilized and transferred in the CFTR as a ‘strict coupling’ mechanism, meaning that one ATP molecule opens CFTR’s gate, ions pass through and the ATP molecule is hydrolyzed and then the gate closes,” Hwang said. “In this new model, we argue that the CFTR uses energy from ATP hydrolysis to carry out its function of chloride flow, but this coupling mechanism is more plastic than we thought and therefore could be subjective to manipulations by drugs such as Vx-770.”

CFTR is part of a family of thousands of active transporter proteins called ABC proteins. Although CFTR may share many structural features with its ABC “cousins,” as Hwang calls them, it has been unclear as to whether CFTR and its cousins may work in a similar manner.

The new idea of how the CFTR utilizes ATP to carry out its function may bear a broader implication because of the evolutionary relationship between CFTR and other ABC transporter proteins. It opens up a wide variety of therapeutic possibilities for other common diseases, such as cancer, heart disease and diabetes, Hwang said, since many other ABC proteins play critical roles in those human illnesses.

“It’s taken years for scientists to solve this particular puzzle about the CFTR protein,” Hwang said. “Our recent study provides evidence that these ABC transporter proteins and CFTR, a chloride channel, are two peas in a pod. Mother nature employs the same structural framework with just a little bit of modification to do two totally different things. From a basic science perspective, it’s a big deal.”

Using electrophysiology techniques available at MU’s Dalton Cardiovascular Research Center, Hwang’s lab studied the opening and closing, or “gating,” of the CFTR at the single-molecule level.  By measuring the electrical current that reflects directly the movement of chloride ions through one single CFTR channel as it opens and closes, Hwang’s lab is able to monitor the activity of a single CFTR molecule in real time.

“Single-channel recording provides a unique opportunity to observe conformational changes in a single CFTR molecule in real time,” Sheppard said. “It’s exciting to think about how the new models proposed by Dr. Hwang and his colleagues explain the action of Vx-770 and other transformational drugs that target the root cause of cystic fibrosis.”

http://medicine.missouri.edu/news/

Vertex Pharmaceuticals Incorporated today announced the      initiation of a global pivotal Phase 3 development program for      fixed-dose combinations of VX-809 (lumacaftor) and ivacaftor in people      with cystic fibrosis (CF) who have two copies (homozygous) of the      F508del mutation in the cystic fibrosis transmembrane conductance      regulator (CFTR) gene. Vertex plans to conduct two 24-week Phase      3 studies to support approval of the combination of VX-809 and ivacaftor      in people with CF ages 12 and older. The studies, TRAFFIC and TRANSPORT,      will each include two treatment groups that will evaluate VX-809 (600mg      QD or 400mg q12h) in combination with ivacaftor (250mg q12h) compared to      a placebo group. Vertex expects to obtain 24-week safety and efficacy      data from both studies and to submit a New Drug Application (NDA) to the     U.S. Food and Drug Administration (FDA) and a Marketing Authorization      Application (MAA) to theEuropean Medicines Agency(EMA), pending study      results.

Vertex also plans to conduct a pharmacokinetics and safety study to      evaluate VX-809 in combination with ivacaftor in children with CF ages 6      to 11 who have two copies of the F508del mutation. The company expects      to use the data from this study for subsequent registration in children      ages 6 to 11 inthe United Statesand is continuing discussions with      European regulatory agencies for patients in this age group.

Vertex will host a conference call for investors and media today,     February 26, 2013at5:15 p.m. EST, to discuss the company’s Phase 3      development plan.

“This Phase 3 development program is a significant advance in our      efforts to develop new medicines that treat the underlying cause of      cystic fibrosis for people with the most common type of the disease,”      saidRobert Kauffman, M.D., Ph.D., Senior Vice President and Chief      Medical Officer at Vertex. “Importantly, these studies will evaluate two      doses of VX-809 in combination with ivacaftor for 24 weeks, and pending      data, enable submissions to U.S. and European regulatory authorities.      People with CF are in urgent need of new treatments, and we are      committed to advancing this combination through Phase 3 development as      quickly as possible.”

Cystic fibrosis is a rare, life-shortening genetic disease for which      there is no cure. Approximately 70,000 people worldwide have CF,      including 30,000 inthe United Statesand 35,000 inEurope. Globally,      nearly half of those with CF have two copies of the F508del mutation.

About the Phase 3 TRAFFIC and TRANSPORT Studies

Vertex plans to conduct two 24-week, randomized, double-blind,      placebo-controlled Phase 3 studies of VX-809 in combination with      ivacaftor. TRAFFIC and TRANSPORT will each enroll approximately 500      people with CF ages 12 and older who have two copies of the F508del      mutation in the CFTR gene, for a total of 1,000 patients. The      studies have the same design and together will be conducted at      approximately 200 clinical trial sites inNorth America,Europe and     Australia.

The primary endpoint of each study is relative improvement in lung      function (percent predicted FEV₁) through 24 weeks of      treatment, compared to placebo. Safety and tolerability will also be      assessed through 24 weeks. Key secondary endpoints through 24 weeks      include absolute improvement in FEV₁, change in body mass      index (BMI) or weight gain, number of pulmonary exacerbations and      improvements in patient-reported outcomes as measured by the CF      Questionnaire Revised (CFQ-R), among others.

Each study will include two combination treatment groups and one placebo      group. The treatment groups will evaluate two regimens of VX-809 (600mg      QD or 400mg q12h) in combination with ivacaftor (250mg q12h). Fixed-dose      tablets that contain both VX-809 and ivacaftor, or placebo, will be used      in both studies. Vertex plans to follow the initial 24-week treatment      period with a separate rollover double-blind extension study where all      eligible patients, including those who received placebo, will receive      one of the combination regimens for up to an additional 96 weeks. The      design of the studies is as follows:

About the Study in Patients Ages 6 to 11

Vertex also plans to conduct a study of VX-809 in combination with      ivacaftor in children with CF ages 6 to 11 who have two copies of the      F508del mutation. The study will evaluate the pharmacokinetics and      safety of the combination for up to 24 weeks. Vertex expects to use the      data from this study, along with data from TRAFFIC and TRANSPORT, for      registration of the combination inthe United Statesin children ages 6      to 11, following registration in patients ages 12 and older. InEurope,      the company is in discussions with regulatory agencies regarding      patients in this age group.

Phase 2 Data Supporting Phase 3 Trial Design

The Phase 3 studies announced today are supported by data from a Phase 2      study of VX-809 in combination with ivacaftor. The two combination      dosing regimens selected for evaluation in Phase 3 were evaluated in      Cohorts 2 and 3 of the Phase 2 study.

Cohort 2: As previously reported, the once-daily (QD)      600mg dose of VX-809 in combination with ivacaftor (250mg q12h) was      evaluated in 21 patients in the second part (Cohort 2) of the Phase 2      study and resulted in statistically significant improvements in lung      function (within group and versus placebo) during the combination dosing      period, as noted below:

Cohort 3: Vertex also evaluated a 400mg twice-daily (q12h)      dosing regimen of VX-809 in combination with ivacaftor in a third cohort      of patients in the Phase 2 study. Cohort 3 evaluated 11 patients who      received VX-809 (400mg q12h) for 28 days followed by VX-809 (400mg q12h)      in combination with ivacaftor (250mg q12h) for 28 days. This cohort was      designed to evaluate safety and pharmacokinetics of the 400mg q12h dose      of VX-809 to support inclusion of this dose in the Phase 3 program.      Cohort 3 also included the randomization of four patients to placebo to      allow for a blinded safety assessment. Three patients completed      treatment in the placebo group. A pharmacokinetic model suggested that      400mg dosing every 12 hours (q12h) of VX-809 would provide a higher      total exposure (AUC; area under the curve) compared to 600mg QD dosing,      and data from Cohort 3 were consistent with this model.

Safety results from the 400mg (q12h) dose group were similar to that of      the 600mg (QD) dose group. In both dose groups, VX-809 was generally      well-tolerated alone and in combination with ivacaftor. The most common      adverse events in both groups were respiratory in nature. In Cohort 3,      one patient in the treatment group discontinued treatment because of a      pulmonary adverse event.

Together, these pharmacokinetic and safety data support inclusion of      VX-809 400mg (q12h) in combination with ivacaftor 250mg (q12h) in the      Phase 3 program to evaluate the effect that higher exposures of VX-809      have on efficacy and safety.

The pattern of lung function response observed in Cohort 3 was similar      to that observed in the 600mg QD dose group in Cohort 2, with a decline      in FEV₁ during the VX-809 monotherapy dosing period followed      by a statistically significant increase in FEV₁ during the      VX-809 and ivacaftor combination dosing period. The within-group mean      absolute improvement in FEV₁ observed during the      combination-dosing period in Cohort 3 was 6.6 percentage points,      compared to 6.1 percentage points for the 600mg QD dose group in Cohort      2.

Additional lung function results for Cohort 3 are provided below:

Study in People with One Copy of the F508del Mutation

In addition to the Phase 3 studies in people with two copies of the      F508del mutation, Vertex plans to conduct an 8-week exploratory Phase 2      study of VX-809 in combination with ivacaftor in people 12 and older      with one copy (heterozygous) of the F508del mutation on one      allele and a second mutation that is not expected to respond to either      ivacaftor or VX-809 alone. This study is designed to provide additional      safety and lung function data on the combination in heterozygous      patients, and will evaluate the twice daily (q12h) combination of VX-809      (400mg) and ivacaftor (250mg).

VX-809 and ivacaftor were discovered as part of a collaboration with     Cystic Fibrosis Foundation Therapeutics, Inc., the non-profit drug      discovery and development affiliate of theCystic Fibrosis Foundation.

About Cystic Fibrosis and the Combination of VX-809 and Ivacaftor

Cystic fibrosis is a rare, life-shortening genetic disease affecting      approximately 70,000 people worldwide, including 30,000 people inthe      United Statesand 35,000 inEurope. The median predicted age of survival      for a person with CF born today is between 34 and 47 years, but the      median age of death remains in the mid-20s. The most common cause of      death among people with CF is lung disease, which results from recurring      infections and chronic lung inflammation.

CF is caused by a defective or missing CFTR protein resulting from      mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)      gene. Children must inherit two defective CFTR genes — one from      each parent — to have CF. There are more than 1,800 known mutations in      the CFTR gene. Some of these mutations, which can be determined      by a genetic, or genotyping test, lead to CF by creating non-working or      too few CFTR protein at the cell surface. The absence of working CFTR      protein results in poor flow of salt and water into and out of the cell      in a number of organs, including the lungs.

In people with the most common mutation in the CFTR gene,      F508del, little-to-no CFTR protein reaches the cell surface. As a      result, thick, sticky mucus builds up and blocks the passages in many      organs, leading to a variety of symptoms. In particular, mucus builds up      and clogs the airways in the lungs, causing chronic lung infections and      progressive lung damage. VX-809, known as a CFTR corrector, is believed      to help CFTR protein reach the cell surface. Ivacaftor, known as a CFTR      potentiator, keeps the CFTR protein channels on the cell surface open      longer to increase the flow of salt and water into and out of the cell.      Globally, nearly half of people with CF have two copies of the F508del      mutation and an additional one-third have one copy of the F508del      mutation.

As announced inJanuary 2013, theFDAgranted Breakthrough Therapy      Designation to the combination regimen of VX-809 with ivacaftor for      cystic fibrosis.

Collaborative History with Cystic Fibrosis Foundation Therapeutics,      Inc. (CFFT)

Vertex initiated its CF research program in 1998 as part of a      collaboration with CFFT, the non-profit drug discovery and development      affiliate of theCystic Fibrosis Foundationin the U.S. This      collaboration was expanded to support the accelerated discovery and      development of Vertex’s CFTR modulators.

About Vertex

Vertex creates new possibilities in medicine. Our team discovers,      develops and commercializes innovative therapies so people with serious      diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to      cure or significantly advance the treatment of hepatitis C, cystic      fibrosis, rheumatoid arthritis and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, Mass., we now have ongoing      worldwide research programs and sites in the U.S., U.K.and Canada.      Today, Vertex has more than 2,000 employees around the world, and for      three years in a row, Science magazine has named Vertex one of      its Top Employers in the life sciences.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the      Private Securities Litigation Reform Act of 1995, including, without      limitation, Dr. Kauffman’s statements in the fourth paragraph of this      press release and statements regarding (i) the clinical studies the      company plans to conduct to evaluate VX-809 in combination with      ivacaftor, (ii) the design of these studies, including the primary and      secondary endpoints and the anticipated number of patients to be      enrolled, (iii) the company’s expectations regarding when data will be      available from these clinical trials, (iv) the potential submission of      the NDA and MAA for the combination therapy and (v) the expectation that      the data from the study in children 6 to 11 will be used for subsequent      registration in the United Statesand the plan to continue discussions      with European regulatory agencies for this age group. While the Company      believes the forward-looking statements contained in this press release      are accurate, those statements are subject to risks and uncertainties      that could cause actual outcomes to vary materially from the outcomes      referenced in the forward-looking statements. These risks and      uncertainties include, among other things, the risks that efforts to      develop VX-809 in combination with ivacaftor may not be successful      because the results of the clinical trials described in this press      release may not support registration or for technical, scientific or      other reasons, that clinical trials may not proceed as planned due to      drug supply, patient enrollment or other issues, and that an adverse      event profile for VX-809 in combination with ivacaftor could be revealed      in further nonclinical or clinical studies and the other risks listed      under Risk Factors in Vertex’s annual report and quarterly reports filed      with the Securities and Exchange Commissionand available through the      company’s website at www.vrtx.com.      Vertex disclaims any obligation to update the information contained in      this press release as new information becomes available.

Conference Call Information

Vertex will host a conference call and webcast today, February 26, 2013      at 5:15 p.m. ETto review the initiation of the Phase 3 pivotal program      studying the combination regimen of VX-809 and ivacaftor for F508del      homozygous patients. The conference call will be webcast live, and a      link to the webcast may be accessed from the ‘Vertex Events’ page of      Vertex’s website at www.vrtx.com.

To listen to the live call on the telephone, dial 1-866-501-1537 (United      StatesandCanada) or 1-720-545-0001 (International). To ensure a timely      connection, it is recommended that users register at least 15 minutes      prior to the scheduled webcast.

The conference ID number for the live call and replay is 15208263.

The call will be available for replay via telephone commencingFebruary      26, 2013at8:00 p.m. ETrunning through5:00 p.m. ETonMarch 5, 2013.      The replay phone number forthe United StatesandCanadais      1-855-859-2056. The international replay number is 1-404-537-3406.

Following the live webcast, an archived version will be available on      Vertex’s website until 5:00 p.m. ETon March 5, 2013. Vertex is also      providing a podcast MP3 file available for download on the Vertex      website at www.vrtx.com.

(VRTX — GEN)

Vertex Pharmaceuticals IncorporatedMedia:Megan      Goulart, 617-341-6992 mediainfo@vrtx.com or Investors:Michael      Partridge, 617-341-6108 orKelly Lewis, 617-961-7530 or Information      for Patients and Healthcare Providers: North America: 1-877-634-VRTX      (8789) medicalinfo@vrtx.com or Outside      North America: 44 (0) 1923 437 672 EUmedicalinfo@vrtx.com

Source:Vertex Pharmaceuticals Incorporated

News Provided by Acquire Media

Augusta, G.A.  –

Cystic Fibrosis is a serious disease that many local people are fighting through. In fact, some of them put their strength to the test at Augusta’s 10k marathon.  News Channel 6’s Courtney Elledge has more.

Augusta’s annual half marathon and 10-k run has a greater meaning to a local group.    A group who knows what it’s like to battle a life – threatening illness.  The 65 Roses Augusta Team is dashing to bring awareness and funding for cystic fibrosis

Stephanie Brantley, coordinator of the run explains, “ I have three children with CF , so it is very close to my heart, and I have great compassion for families who go through all the trials and tribulations. So it helps to see an impact through financial assistance and research.”

Matthew Brantely is living with the disease. He says, “It needs to be promoted more, I mean CF is more like cancer; it’s a long – term illness. You’re diagnosed for life, and so this race is helping to bring awareness. It’s pretty prevalent among people in the United States.”

Cystic Fibrosis is one of the most chronic lung diseases in children and adults.   It’s passed down genetically and causes a thick mucus to build up in the lungs, pancreas and other parts of the body. Advances in medicine and early detection by testing pregnant mothers can control the disease—but that comes with a high price tag.

Stephanie Brantley says, “ Kalydeco is a new drug, which actually works a lot like ensiling would for diabetic patients… this is a drug that works at the actual cell level. “

Today, the average life span for people with CF is approximately 37 years. Patients say that is something to never think about. They simply live for today.

To learn more about the illness and how you can donate  click here http://milesforcf.org/augusta/

http://www2.wjbf.com/news/2013/feb/24/65-roses-sprint-cystic-fibrosis-ar-5670624/

SIOUX CITY | “There but for the grace of God go I” might be the motto of a group of students who hope to draw attention to a debilitating disease.

The Sioux City Community School District’s Health Sciences students are organizing a Great Strides Walk for Cystic Fibrosis on March 9. The young people are members of Health Occupation Students of America, which has adopted the Cystic Fibrosis Foundation as their national fundraiser.

“The people who are affected with this terrible disease are young people like us,” said West High student Kelsi Wilkie. “Some of them don’t get the chance to live past the age of 20 or 30 years old. We want to change those statistics.”

“We were introduced to the project in August of 2012,” explained Tia Adamson of West High School. “The National Service Project for HOSA this year and next year is the Cystic Fibrosis Foundation. After doing a little research on Cystic Fibrosis, we decided that we wanted to make a difference, get the community involved, and raise awareness of Cystic Fibrosis.”

Heather Carlson teaches the Health Careers and Teams class for the sophomores and also serves as their HOSA adviser.

“We are located at the ESC building, 627 4th St. and get students from East High, West High, and North High,” she explained. “The students receive dual credit for the classes they take here. They get college credit along with high school credit.”

Carlson explained the students can graduate from high school with a Pharmacy Technician certification, a Certified Nursing Assistant certification, or a Surgical Technician certification through the program.

“The high school pays for these college credits,” she said. “So, it is free college credits for students.”

All of the students who have been the main planners for this walk are high school sophomores, Carlson noted.

“They are all interested in a health-related career after graduation,” she said. “All of the planning for this has been done in their free time and on a volunteer basis. They are very self-motivated students and want to make the world a better place.”

Since last fall the students have been fundraising and trying to get the word out regarding their walk. They sold suckers and holiday ornaments to raise money. They also offered their gift wrapping skills at Barnes and Noble in December of last year.

Carlson has been very surprised at the community support for the walk.

“We have had many people contact us from the community and want to get involved in any way possible,” she said.

“Another thing that has surprised me is how little people know about cystic fibrosis,” Carlson continued. “Many people have heard of cystic fibrosis but do not know much about it. They are not aware of how many medications these people have to take and how many other treatments they have to do on a daily basis.”

“A number of people die every year from Cystic Fibrosis and not a lot of attention is given to this disease,” said Nicole Mutchler of East High. “Our biggest challenges have been getting people involved, getting people together, and getting the word out about our efforts.”

North High student Nayelie Valenzuela pointed out the greatest joy of taking on this project has been knowing that the group is making a difference.

“When people from the community contact us and want to help, we know we are touching lives,” she said.

“Our greatest joy, we think, is yet to come though,” Wilkie clarified. “When we see the faces of people living with Cystic Fibrosis the day of the walk, we will be able to put faces to those who we are making a difference for.”

http://siouxcityjournal.com/news/local/fox-sioux-city-students-draw-attention-to-cystic-fibrosis/article_c7ff3874-5ecf-5271-bb79-207cc30e3c9f.html

BALTIMORE (WJZ) — It’s a unique fundraiser and it will bring hundreds of people together Saturday at Boys’ Latin School.

Ron Matz reports thanks to one determined family and a dozen local schools, thousands of dollars will be raised in the fight against cystic fibrosis.

It’s dodgeball for a cure. Molly Danko and her sister Bridget came up with the idea in memory of their mother Stacy, who was 44 when she died of cystic fibrosis.

“In my freshman year at Bryn Mawr, I started a cystic fibrosis club at the school. We raise money all year. We have fundraisers and bake sales. We organize a team for the CF Great Strides walk coming up in May,” Molly Danko said. “My mom taught me that if you believe in something, go for it. I believe that every little thing counts and we can all come together to help make a change for CF and help people better their lives.”

“I was 11 when my mom passed away. She loved her kids. She didn’t live like she had CF; she lived like a normal person. She didn’t let it get in her way and she lived every day to her fullest,” Bridget Danko said.

Stacy was a devoted mom and a nurse.

“She was a nurse in critical care at Hopkins and at Shock Trauma,” Molly Danko said.

The players know the importance of what will happen here.

Saturday’s Dodge For A Cure will bring 12 schools and 240 participants to Boys Latin, all raising money to benefit CF.

“Our mom passed away from CF and CF has been a big part of our lives and we like to give back because they did so much to help my mom. This event is big for us because we can give back to them and help them raise more money,” Bridget Danko said.

In memory of a woman who touched thousands.

“My mom passed away four years ago from the genetic disease cystic fibrosis. She fought hard every day. She was just a great example to everybody around her. She walked into a room and could light it up,” Molly Danko said. “She had a positive attitude and lived every day to the fullest like it could be her last. She never let CF bring her down.”

Besides the tournament, there will also be food, music, prizes, raffles and t-shirts. Saturday’s Dodge For a Cure at Boys’ Latin will be held from 4:30-8 p.m.

http://baltimore.cbslocal.com/2013/02/19/boys-latin-to-hold-unique-fundraiser-saturday/

After running about 24 miles during a race last summer, Joshua Skampo realized that his time finally might be good enough to qualify for the famed Boston Marathon this April.

It was June in Charlevoix when the 30-year-old Monroe resident needed to complete the 26-mile race in 3 hours, 5 minutes or less. And nothing — not the aching and burning sensation in his legs or the cystic fibrosis that has limited his lungs since birth — would keep him from his mission.

“I knew I was close,” Mr. Skampo said. “I knew I had about 30 seconds to play with. This was my shot.”

He crossed the finish line that summer day at 3 hours, 4 minutes, 12 seconds, good for eighth place out of 334 runners. With 48 seconds to spare, Mr. Skampo achieved a goal few runners have accomplished: qualifying for the prestigious Boston Marathon.

And, remarkably, he did it with only 65 to 70 percent lung function.

“It’s the biggest marathon around,” Mr. Skampo said. “They don’t let just anybody into it.”

Cystic fibrosis is an incurable disease that causes thick, sticky mucus to build up in the lungs. It is deadly, and the average lifespan for people with CF who live to adulthood is approximately 37 years.

“I don’t know what normal breathing feels like,” he said. “It’s like you have pneumonia all the time.”

But Mr. Skampo refuses to dwell on it or allow it to dictate his life. Running, he said, is therapeutic and actually helps clear his lungs. So he started in middle school and gradually increased his distance to marathons as he got older.

“It’s what keeps me healthy,” he said. “I have to run today so I can breathe tomorrow.”

He runs to and from work. He runs in races. He runs for fun. He runs to clear his lungs, but he’s also competitive. That’s why it was important for him to beat the 3 hour, 5 minute mark in Charlevoix last June; he wants to race in Boston.

His goal is to break the three-hour mark. If he does, Mr. Skampo believes he could finish in the 1,000th place range out of between 23,000 and 25,000 competitors.

Despite his chronic lung disease, Mr. Skampo doesn’t want special consideration. Although he knows of only one other marathoner with CF — a man in Colorado — he prefers to remain low-key, so he hasn’t researched that type of information. Instead, he focuses on how he can improve his time.

With only about two months until Boston, Mr. Skampo is in the midst of training. An engineer at Fluid Equipment Development Co. (FEDCO), Mr. Skampo commutes in his running shoes several times a week. He’ll run about 55 to 60 miles a week and is on pace to run 2,600 miles for the year, his most ever. He grew up in Adrian, but he and his wife, Melissa, have lived in Monroe for about five years.

Although he wears bright fluorescent colors, motorists don’t always see him or pay attention. He had a close call once when a car bumped him, and sometimes he has to endure taunts or items thrown at him. But he endures. Mr. Skampo just keeps going.

In addition to the qualifier in Charlevoix, Mr. Skampo has run three other marathons in his life. And, on April 15, he will compete in his fifth, which also will be his most important race.

“(The Boston Marathon) has always been a goal of mine,” he said. “I’m excited. I want to put in the work and do my best. I just want to do my best.”

Joshua Skampo is raising funds for cystic fibrosis research. To donate, visit www.crowdrise.com/JoshRockstoBoston.

http://www.monroenews.com/news/2013/feb/19/monroe-man-cystic-fibrosis-qualifies-boston-marath/