Category: Medical research

Vertex reports great results for its latest trials targeting double DF508 and single DF508 combos

Hopefully by now you’ve all seen the fantastic results that Vertex reported last week regarding their latest trials with precision therapy for those with both double DF508 and a single DF508 mutation combo. Vertex shares are up 21% and the reported results are pretty exciting. Although the trials were for patients 18 and older, it sounds like they’re fast tracking the next late stage trials (earmarked for early 2018) so let’s hope pediatric trials follow swiftly. Continue reading “Vertex reports great results for its latest trials targeting double DF508 and single DF508 combos”

John Hopkins’ CF research review

If you’re looking to keep abreast of the latest research on key topics, the John Hopkins CF Centre in the US publishes a regular newsletter called e-cysticfibrosis review which basically publishes a peer review of a whole bunch of research into critical care topics.

It’s set up for medical care teams to subscribe to but anyone can join it. They’ve just done a brief summary of pseudomonas research and treatment protocols for anyone who is interested.

If you’re keen, you can sign up here  e-cysticfibrosis review


A few notes from the latest CFRI conference in California

Screen Shot 2015-08-13 at 8.43.51 AMLast week the annual CFRI conference was held in Redwood City California. For those of you who are not familiar with CFRI, it’s a terrific organisation that funds cystic fibrosis research, provides educational and personal support, and spreads awareness of cystic fibrosis.

Their website hosts a bunch of terrific content from research paper, presentations and key learnings to events and links with other key CF networks. It’s well worth your while getting on there and having a look. They also held a pediatric conference earlier in the year which had some incredible content specifically related to pediatrics. Do yourself a favour and get onto that content when you have a moment, its positive, uplifting but really informative. You can find that here

Screen Shot 2015-08-13 at 8.44.09 AMI travelled to the most recent conference last week which was fantastic. About 200 people went, a combination of speakers that included CF doctors and program directors, a physiotherapist, a social worker, an infection control expert and CF nurse / clinic co-ordinator who has devoted her life to CF; plus about 150 CF parents.

I took a heap of notes so that I could share the content with you all. You can download my notes here.

CFRI summary notes

Please keep in mind that there was a mountain of info so I’ve done my best to try and record / remember as much as I could in each session but there may be some things missing. There’s a bit more to put down on paper but this is the majority of the sessions as I remember them.

If you have any questions please give me a shout at

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Keeping CF lungs infection free

A must watch for any CF paediatric parent.

Different doctors give different advice. So do different clinics. There’s no getting around it. We do not have an agreement on modes and models of care from one country to the next or even one clinic to the next.

As parents we can’t avoid the responsibility of making the most informed decisions possible, which is why we all need to seek out information and experiences beyond our own as much as we can. The real reason is not just hearing other doctors speak but also listening to other parents and children with CF. These are the people on the battlegrounds at the forefront of day-to-day care of this disease, just as we are. The CFRI is a terrific organisation that offers loads of resources and they recently had a paediatric conference on “Tools to help your CF child thrive” – this is the first presentation from that series. I’m going to post them one by one with a short summary over the next few weeks.

So here’s a summary of the first session :

What are the things we need to do to keep CF lungs healthy: Tips from a CF researcher who is also the parent of a CF child  Continue reading “Keeping CF lungs infection free”

ORKAMBI given the green light for FDA Review

May 12, 2015

Food and Drug Administration Advisory Panel Voted 12 to 1 to Recommend Approval of ORKAMBI™ (lumacaftor/ivacaftor) to Treat People with Cystic Fibrosis Ages 12 and Older Who Have Two Copies of the F508del Mutation

FDA decision expected by July 5, 2015

Approximately 8,500 people with cystic fibrosis in the U.S. have two copies of the F508del mutation and are ages 12 and older

Pills In JarsBOSTON–(BUSINESS WIRE)– Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the U.S. Food and Drug Administration’s (FDA) Pulmonary-Allergy Drugs Advisory Committee (PADAC) voted 12 to 1 to recommend that the FDA approve ORKAMBITM (lumacaftor/ivacaftor) for use in people with cystic fibrosis (CF) ages 12 and older who have two copies of the F508del mutation in the CFTR gene. Advisory committees provide the FDA with independent scientific and medical advice on safety, effectiveness and appropriate use of potential new medicines. The FDA is expected to make a decision on the approval of ORKAMBI by July 5, 2015 under the Prescription Drug User Fee Act (PDUFA). The FDA is not bound by the committee’s recommendation but often follows its advice. If approved, ORKAMBI will be the first and only medicine to treat the underlying cause of CF for eligible people with CF ages 12 and older with two copies of the F508del mutation in the CFTR gene. People with two copies of the F508del mutation represent the largest group of people with CF. There are approximately 8,500 people ages 12 and older with two copies of the F508del mutation in the U.S.

“Today’s positive recommendation brings the cystic fibrosis community one step closer to potential approval of the first medicine to treat the underlying cause of this disease for many more people,” said Jeffrey Chodakewitz, M.D., Executive Vice President and Chief Medical Officer at Vertex. “We look forward to continuing to work with the FDA and other regulatory agencies throughout the world to make ORKAMBI available to eligible patients as soon as possible.”

Cystic fibrosis is a rare genetic disease that is caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene. The defective or missing proteins result in poor flow of salt and water into and out of the cell in a number of organs, including the lungs. In people with two copies of the F508del mutation, the CFTR protein is not processed and trafficked normally within the cell, resulting in little to no CFTR protein at the cell surface.

ORKAMBI is a combination of lumacaftor, which is designed to increase the amount of functional protein at the cell surface by addressing the processing and trafficking defect of the protein, and ivacaftor, which is designed to enhance the function of the CFTR protein once it reaches the cell surface. ORKAMBI is an oral medicine that, if approved, would be taken as fully co-formulated tablets that contain both lumacaftor and ivacaftor.

Vertex (VRTX) Soars After Hours as FDA Panel Backs Cystic Fibrosis Drug Orkambi

Vertex Soars After Hours as FDA Panel Backs Cystic Fibrosis Drug Orkambi
May 12, 2015
By Riley McDermid, Breaking News Sr. EditorA delegation of executives of Vertex Pharmaceuticals (VRTX) successfully argued today before the U.S. Food and Drug Administration (FDA) Pulmonary-Allergy Drugs Advisory Committee that its cystic fibrosis drug Orkambi has merit, causing the panel to vote 12-1 to approve the drug. For a complete breakdown of the questions asked and how the panelist voted, please click here.

There had been some concern the treatment may not be approved after notes form the panel leaked last week showing the FDA had significant concerns about the efficacy or Orkambi. But investors who had been waiting all day for the news and applauded the decision, pushing Vertex up almost 9 percent in aftermarket trading.

“Today’s positive recommendation brings the cystic fibrosis community one step closer to potential approval of the first medicine to treat the underlying cause of this disease for many more people,” said Jeffrey Chodakewitz, executive vice President and chief medical officer at Vertex. “We look forward to continuing to work with the FDA and other regulatory agencies throughout the world to make ORKAMBI available to eligible patients as soon as possible.”

One of the ingredients of Orkambi is ivacaftor, which Vertex markets under the name Kalydeco. Kalydeco is used to treat patients with one specific mutation in the CFTR gene, not including F508del, the most common cystic fibrosis mutation. Orkambi combines ivacaftor with lumacaftor.

Neither lumacaftor nor ivacaftor, by themselves, help cystic fibrosis patients with the F508del mutation. But a combination of the two has shown positive results in clinical trials and the FDA agreed that the benefits were large enough to allow approval.

“Despite the questions raised by the FDA and the panelists’ willingness to consider the FDA’s arguments this morning (after multiple speakers during the open public hearing), the panelists this afternoon came out in general support of Orkambi,” wrote biotech analyst Mark Schoenebaum in a note Tuesday.

“The panelists generally agree that a comparative efficacy study of Orkambi vs Kalydeco in homozygous F508del patient could be done post-approval if necessary,” he said.

Kalydeco generated $464 million in revenue last year. In the U.S., there are about 30,000 CF patients, but only 7 percent have the specific gene mutation that Kalydeco treats. If Orkambi is effective and gets approved, it could potentially be used to treat about 15,000 of those patients in the U.S. alone, although more likely be applicable about 8,500 patients 12 years and older. However, potential revenue if approved, is projected at $5 billion within a couple years.

The Vertex portion of the presentation was concluded by Bonnie Ramsey, director of the Center for Clinical and Translational Research at Seattle Children’s Hospital and the Washington School of Medicine, saying Orkambi “will have a major impact” on her CF patients.

News last Friday that the FDA’s Pulmonary-Allergy Drugs Advisory Committee has released its briefing notes ahead of the meeting initially spooked the market, but the company has roared back as Wall Street agreed the document is an overall positive.

When parsed thoroughly the documents appeared to show the FDA believes that there is a statistically significant benefit over placebo in FEV1 but has questions about the small treatment effect and the lack of ivacaftor monotherapy and lumacaftor monotherapy controls in the Phase III trials, said analysts.

The lead biotech analyst at Citigroup, Yaron Werber, said a closer look at the FDA’s notes show the regulator is generally open to the idea of approving Orkambi.

“Given that Orkambi has Breakthrough designation, which provides for enhanced interaction, FDA notes that they and EMA agreed with the study designs and continuously provided constructive guidance,” wrote Werber.

“As such we believe that FDA needs to raise this question for discussion but is supportive of the trial design. The key question is whether the benefit is clinically meaningful. We believe that the AdCom will vote positively for approval of Orkambi given the lack of alternative treatment options for cystic fibrosis patients homozygous for the F508del mutation in the CFTR gene.”

Big news for DF508 carriers

two-pills-500-466x298On May 12, 2015, the Pulmonary-Allergy Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) will hold a hearing to discuss Vertex Pharmaceuticals’ new drug application for approval of the lumacaftor/ivacaftor combination therapy for the treatment of cystic fibrosis in patients age 12 years and older who are homozygous for the F508del mutation.

The results of a phase 3 clinical trial with lumacaftor and ivacaftor showed statistically significant improvements in lung function and other markers. Sue Landgraf, CFRI’s executive director, will address the committee during oral presentations from the public, advocating for FDA approval of the combination therapy.

To read the FDA’s announcement of the hearing, click here.


What were the results of the ivacaftor and lumacaftor Phase 3 clinical trials?

Participants in the Phase 3 trials who received the combination treatment showed significant improvements in lung function and other important health measures, compared with those on placebo, and these gains were sustained throughout the 24-week trials.

Both trials tested the same two doses of lumacaftor in combination with ivacaftor. All groups of participants receiving the treatment achieved the trials’ primary endpoint goal of a mean absolute improvement in lung function (measured by FEV1), with a range of 2.6  4 percentage point improvement across the groups.

Those taking the combination treatment also had significant improvements in multiple secondary endpoints, including a mean relative improvement in FEV1 between 4.3 and 6.7 percent; improved weight gain; and significant reductions in the rate of pulmonary exacerbations and associated hospitalizations and IV antibiotic use.

How were the Phase 3 clinical trials conducted?

The two six-month Phase 3 clinical trials studied the combination treatment in people with two copies of the F508del mutation ages 12 and older. In total, more than 1,100 study volunteers participated at nearly 200 clinical trial sites in North America, Europe and Australia.

Both trials tested the same two doses of lumacaftor in combination with ivacaftor. Participants were monitored and given laboratory tests and surveys to measure lung function, body weight and body mass index, hospitalization rates and overall health and quality of life.

The trials were “double-blinded:” neither the participants nor the trial researchers knew which groups received the drug combination and which group received placebo.

Most Phase 3 trials are about one year long. However, the combination trials were completed in about half the time typically required for a Phase 3 trial, following the FDA’s awarding the potential combination treatment “Breakthrough Therapy Designation,” intended to speed the development of select potential therapies that treat life-threatening diseases or conditions.

Will the combination treatment be available to people with CF who are younger than 12 years of age?

The drug combination must be tested in people under age 12 to determine its safety and efficacy in this patient group. Vertex plans to conduct a clinical trial of the combination treatment in people with CF with two copies of the F508del mutation ages 6 to 11 in the first half of 2015.

Why weren’t the results from the Phase 3 combination trials as good as the results from studies of ivacaftor alone in people with G551D?

The potential combination treatment targets a more complex problem in CF than Ivacaftor targets.

Ivacaftor has been approved for people ages 6 and older with the G551D mutation and several closely related mutations. In people with these mutations, the CFTR protein is at its proper place at the cell surface but does not function normally. Instead, it acts like a locked gate. Only one drug is needed to help increase CFTR activity and unlock that gate, allowing the normal flow of salt and fluids that helps thin the thick mucus that builds up in the lungs of people with CF.

In people with the most common CF mutation, F508del, a series of problems prevents the CFTR protein from taking its correct shape and reaching its proper place on the cell surface. Addressing these problems requires a multi-pronged approach that takes place in different parts of the cell. Lumacaftor is designed to help move the defective CFTR protein to the cell surface, while ivacaftor improves its function once it is there.

Is this drug combination a cure for CF?

The combination treatment is not a cure for CF. However, based on the results from the Phase 3 trials in people with two copies of the F508del mutation ages 12 and older, the two drugs in combination have been shown to significantly improve lung function and other important measures of the disease.

The Phase 3 results further validate findings from other late-stage studies that have demonstrated it is possible for an oral drug to improve key symptoms of CF by addressing the defective CFTR protein caused by mutations in the CF gene.

What is the current status of Vertex’s FDA approval application as it stands now?

On Nov. 5, 2014, Vertex Pharmaceuticals Inc. submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for approval of the combination of ivacaftor (Kalydeco™) and the potential therapy lumacaftor (VX-809). The potential combination drug is designed for people with cystic fibrosis ages 12 and older who have two copies of the most common mutation of cystic fibrosis, F508del.

Results from Phase 3 trials of the combination drug showed that people with two copies of the F508del mutation ages 12 and older who received the treatment had significant improvements in lung function and other key measures of the disease.

Both ivacaftor and lumacaftor are designed to treat the underlying cause of CF — a defective protein, called CFTR, caused by mutations in the CF gene.

Vertex has requested a priority review of the combination drug, which, if granted, could shorten the FDA review timeframe from approximately 12 months to 8 months.

An update on Kalydeco

Vertex pharmaceuticals, the company who pioneered the revolutionary Kalydeco drug treatment currently available for people with the GFF1D mutation – around 4% of the population, will be presenting further updates on how the drug works for people who are homozygous for the F508del mutation (the more standard mutation) at this year’s North American Cystic Fibrosis conference currently being held in Atlanta.

Vertex Pharmaceuticals will be presenting 15 abstracts at the 28th Annual North American Cystic Fibrosis Conference (NACFC) held in Atlanta from October 9-11. Each abstract is from Vertex’s cystic fibrosis research and development program. Data will primarily be related to TRAFFIC and TRANSPORT clinical trials, which were phase 3 rollover studies evaluating lumacaftor and ivacaftor combination therapy.

According to a news release from Vertex, presented data will include the first interim data from patients who completed TRAFFIC and TRANSPORT, which were highlighted previously on Cystic Fibrosis News Today. These studies were for individuals homozygous for the F508del mutation. Data from this subtype of cystic fibrosis patients, who were on combination lumacaftor and ivacaftor therapy for 24 weeks, were previously presented and will be revisited at NACFC. Data concerning combination therapy will be related to drug distribution in the body, safety in children on the treatment, and the effects of using bronchodilators while on concomitant combination therapy.

Presented studies will also focus on children receiving ivacaftor treatment. These studies evaluated individuals with R117H residual functional mutations who benefit from the potenitation mechanism of ivacaftor. Topics include the effects of ivacaftor on forced expiratory volume in one second (FEV1), the distribution of ivacaftor throughout the body following administration, and the effects of ivacaftor on patient weight.