Transplantation Firsts, Part 4 – First Lung Transplants

The period of the 1950s and 1960s was clearly the golden age of transplantation attempts, successes and failures.  From liver to kidney to hearts, from procedures on animals to humans, many trials based on technologies of the time allowed for the unthinkable.  Due to the obvious importance of the lungs, as physician William Harvey stated in a mid-17th century publication, “there is nothing living that does not breathe nor anything which breathing which does not live”, it was only a matter of time before a method was developed to transfer lungs from one person to another.  This first successfully occurred in humans during the 1960s.

The former Soviet Union was the genesis of experimental lung transplantation in the mid-1940s, beginning with animal experimentation.  Among those studying this phenomenon was Vladimir Demikhov, noted to be one of the pioneers of organ transplantation (  Lung transplantation experiments were first begun as combined heart-lung transplantation procedures performed by Demikhov from 1946 to 1955, when he accomplished 4 and 6-day survival periods with dogs being his subjects (

Dr. James Hardy was another pioneer in the lung transplantation field.  In preparation for conducting human lung transplants, Dr. Hardy, too, utilized dogs, as he attempted approximately 400 transplant experiments on those subjects.  Recognizing the inherent risks of a lung transplants in the 1950s and 1960s, Dr. Hardy would only conduct this procedure on someone in failing health.  He found such a patient when the doctor performed the first human lung transplant in 1963 in Jackson, Mississippi on a man suffering from lung cancer.  This recipient passed away 18 days after the transplant as a result of kidney failure (

This attempt illustrated that lung transplantation held many barriers in the 1960s which had yet to be conquered, although it spurred subsequent attempts.  Over the following ten-year period, there were 36 transplants performed worldwide.  However, of those recipients, most died within a few days, with just two surviving more than a month.

Almost twenty years after that first transplant attempt, two episodes brought about the first long term successes in this field.  It was in 1981 that Dr. Norman Shumway conducted three heart-lung transplants at Stanford University.  Two of those recipients survived for more than a year.  Two years later, in 1983, the Toronto Lung Transplant Group performed the first successful lung transplant, which took place on a 58-year-old man with pulmonary fibrosis.

Since then, the occurrences of lung transplants have increased exponentially.  In 1987, approximately 45 transplants were performed, and by 1990, over 400 were performed worldwide.  Commensurate with the increased frequency of the transplants were improved outcomes.  To note, the median survival rate of patients transplanted between 2000 and 2006 was 5.5 years compared to 4 years for those transplanted between 1998 and 1994.

Finally, since the early 1990s, more than 25,000 lung transplants have been performed worldwide (

Until later.

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Topic for Saturday, March 3rd posting – Organ Preservation Practices

Transplantation Firsts, Part 3 – First Heart Transplants

It is logical reasoning to recognize that throughout history, many doctors saw the human heart as the base of the soul.  It is for that reason that medical professionals found the heart too fragile to manipulate.  However, near the beginning of the 20th century, research of heart transplantation and several operative attempts in that field were pursued in several countries, ranging from the United States to Russia, with the goal of eventually conducting a human heart transplant.  As with many organs, the first successful human to human heart transplantation finally occurred in the middle of the 20th century.

Although modern medical research and advances historically have occurred in the West, the first notable workings in the field of heart transplants began in Russia.  By 1940, Vladimir Demikhov had developed an artificial heart that could substitute for a dog’s heart, functioning for as long as 5 ½ hours.  He also began to transplant hearts into the chests of dogs in 1946, eventually perfecting the process so that some animals would survive for as long as 32 days after the transplant.  Additionally, Demikhov began the first series of combined heart-lung liver transplants from between 1946 to 1955.  As it turned out, his research on these subjects, which could have possibly assisted and advanced Western medical professionals who were attempting some of the same types of procedures, was unfortunately not published in English until 1962 (

As a precursor to heart transplantation, what could be seen as the first steps in heart surgery was performed by military surgeon Dwight Harken during World War II, as he removed shrapnel and bullets from the hearts of approximately 130 soldiers.  No fatalities occurred as a result of those procedures.  On a similar note of first steps, in 1953, Dr. John Gibbon Jr. of Philadelphia repaired a hole in the heart of an 18-year-old patient, using a heart-lung respirator to keep the individual alive; thereby providing a pathway for future open-heart surgeries (,8599,1939493,00.html).

It was nearly 15 years from that time until the next significant advancement in heart transplantation.  On December 2, 1967, a 25-year-old woman suffered a fatal brain injury in a car accident.  The following day, based on techniques originally developed by Stanford researchers in the 1950s, South African Dr. Christian Barnard performed the world’s first human to human heart transplant.  The recipient, a 53-year-old grocer, survived for 18 days post-transplant before succumbing to double pneumonia.  Demonstrating the success of the surgery and technique was that the donated heart was functioning normally at the time of the recipient’s death.

The news of that operation spread, and colleagues began to perform similar heart transplantation surgeries.  During the span of two years, approximately 60 teams conducted these transplants on roughly 150 patients.  To prevent organ rejection, large dosages of immunosuppressant medication were administered to the heart recipients.  However, the abundance of these drugs caused the individuals to be susceptible to dangerous infections.  As such, the one-year survival rate for heart transplant patients in the late 1960s was 20%.  The reality of those results is reflected that the number of surgeries fell to 18 in 1970 from 100 in the previous year.

Despite that seemingly insurmountable barrier, Dr. Norman Shumway of Stanford and Dr. Barnard continued to pursue methods of improving this transplantation process.  Dr. Shumway worked to develop a technique that enabled the surgeon to identify when the body was about to reject the organ, at which point the dosage of immunosuppressants could be adjusted.  Accordingly, nearly 200 heart transplants were undertaken at Stanford from between 1968 and 1980.  Applying Dr. Shumway’s practices, about 65% of his patients survived for at least a year, with 50% surviving for five years.  Similar positive outcomes were recognized during that same time period with work conducted by Dr. Barnard and his team, as they improved protection and preservation of the heart prior to transplant (

These studies led to the biggest advances in heart transplantation to date, which occurred in the 1980s.  In addition to Dr. Richard Jarvik implanting the first artificial heart in 1982, the most significant advances occurred two years later, when the first successful pediatric heart transplant took place on a four-year-old boy.

Toward the end of 1984, the historic “Baby Fay” heart procedure was performed.  Conducted by a team at California’s Loma Linda University Medical Center, a walnut sized bamboo heart was transferred into the chest of 12-day old Stephanie Fay Beauclair.  Stephanie survived for 21 days before she passed away from kidney failure.

The key to the long term success of heart transplantation operations was the discovery and proper application of immunosuppressant drugs.  In 1958, Dr. Keith Reemtsma of Tulane University was the first to show in laboratory settings that immunosuppressant agents would prolong heart transplantation survival, while in 1980, Dr. Shumway began using the anti-rejection drug Cyclosporine A in his clinical practice (

In December of that year, it is recorded that the one, two, and three-year survival rates for Dr. Shumway’s transplant patients at Stanford using this med was 63%, 56%, and 52%.  Five years later, each of those rates rose by more than 15%.  The introduction of Cyclosporine A played a significant role in allowing heart transplantation to its current level of success and acceptance.

Until later.

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Topic for Saturday, February 17th posting – Transplantation Firsts, Part 4 – First Lung Transplants

Transplantation Firsts, Part 2 – First Liver Transplants

The liver was seen as a sort of imperial organ throughout history in some cultures.  In fact, the German word for liver is “leber”, which is derived from the verb “to live”.  The Roman anatomist, Galen, who lived in 2nd and 3rd century, referred to the organ as the principal organ of the human body.  Avicenna, an Islamic medical philosopher from the 10th and 11th century, artfully noted the liver as “the seat of the nutritive or vegetative faculties.” (…/liverpages/livergallbladderspleen.html).  It was during the mid-20th century that the secret to successfully transplanting this noble organ was unlocked.

As was the case with various organ transplantation attempts, the first experiments to transplant the liver were performed on animals.  Dogs were the specialty animals for early liver replacement trials.  C. Stuart Welch of Albany Medical College wrote about inserting a liver into a dog in 1955, while three years later, Francis Moore described the first surgery on a dog where the original liver was removed and replaced by a donor liver.  Further, Dr. Thomas E. Starzl performed over 150 dog experiments to investigate the various issues involving liver transplantation.

The early 1960s was a time of the first human liver transplant attempts, but none were successful.  To note, Dr. Starzl performed five such human liver replacement attempts, with one patient dying during the surgery due to massive blood loss, with the remaining four living from between 6.5 to 23 days following the procedure (  These cumulative failed attempts led to a moratorium on liver transplant activity in humans until the summer of 1967.  Undeterred, Dr. Starzl did not stop pursuing liver transplantation activities, but under a different model, as he and his colleagues performed three chimpanzee to human children procedures between 1966 and 1973.  True to practice, none of those transplants were successful.

The much sought-after success in this realm finally occurred in July 1967, as Dr. Starzl, termed “The Father of Liver Transplantation”, transferred a liver into nineteen-month-old Julie Rodriguez.  This girl became the first person to survive for more than a year, post liver transplant, only to succumb to a type of liver cancer 400 days later (

At the time, 70% of deaths occurred in liver transplantation due, in large part, to organ rejection.  The common immunosuppressant drugs utilized at the time were steroids and azathioprine, and based on the lagging success rate, were not largely effective (  As such, the one-year survival rate was at 15% in 1970.

A significant barrier to the success of liver transplantation was pierced with the discovery of the immunosuppressant drug Cyclosporine by J.F. Borel in 1976.  Cyclosporine was effective, as it allowed selective immunoregulation of T cells without excessive toxicity (  An illustration of the drug’s effectiveness is exhibited by a report showing that prior to the discovery of Cyclosporine, the one year survival rate following liver transplantation was between 30% to 50%, while the survival rate of that same period of time climbed to 74% for the first 1,000 recipients treated with Cyclosporine in the early 1980s ­at the University of Pittsburgh (

This type of procedure obtained a significant boost in the medical field in 1981, when C. Everett Koop, the United States Surgeon General, initiated an international conference for liver transplantation.  The input provided from experts, including those from several European centers, led to the consensus that liver transplantation had become a “clinical service”, as opposed to the experimental service as it had been previously recognized.

Finally, a new immunosuppressive drug Tacrolimus, which promotes the development of T cells vital to the body’s learned immune system, was introduced in 1990.  It was later found that when Tacrolimus is used in conjunction with Cyclosporine, this combination further reduced instances of organ rejection when compared to past anti-rejection medications.

As of 2015, more than 10 million liver transplantations had been performed worldwide, with patient survival within the first year ranging from roughly 80% to 90%.

Until later.

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Topic for Tuesday, February 6th posting – Transplantation Firsts, Part 3 – First Heart Transplants

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Transplantation Firsts, Part 1 – First Kidney Transplants

Transplantation Firsts, Part 1 – First Kidney Transplants

There have been many stops and starts with regard to transplants, in general.  Kidney transplants were among the first to be attempted in modern times.  Transplants of that organ were begun between animals in the early 1900s, followed by unsuccessful attempts to transplant animal kidneys into humans.  It was not until the mid-20th century that the first successful human to human kidney transplantation was performed, which, in turn, set the standard for more advanced successful kidney transplants in the future.

The first successful kidney transplant of any kind was performed in Austria in 1902, when a dog’s kidney was transplanted into another dog’s neck.  The kidney lasted for five days.  The second attempt at a kidney transplant, albeit unsuccessful, was conducted in the same year, with the exchange of organs between a goat and a dog (  France was the location in 1909 for several animal to human kidney transplants attempts involving monkeys, dogs, goats, and lambs, but none achieved the desired results.  The first human to human kidney transplant occurred in 1936 by Ukrainian doctor Yu Yu Voronoy, but that patient died 48 hours later without making urine, a milestone which would have indicated some success with the procedure (

In the first half of the 20th century, kidney transplants were intended to be temporary, and only meant to last until the original kidney recovered.  Science had not yet advanced to the point where methods for the body to permanently accept the organ had been discovered.

However, in 1954, the first successful living human to human kidney transplant took place between identical twins in Boston, with that kidney functioning for eight years.  The fact that the individuals were twins was the key to allowing this procedure to be successful, as the body of the twin who received the organ did not view the donated liver as being foreign.  As a result, the body’s immune system did not cause a reaction and a subsequent rejection of the transplanted organ.

Four years later, in 1958, the first kidney transplantation using immunosuppressants, also referred to as anti-rejection drugs, was performed.  Without these drugs, the body sees the new organ as foreign, and either damages or destroys it.  True to its name, the immunosuppressants resist the body’s immune system’s ability to reject the organ.  These anti-rejection drugs served to overcome the biggest obstacle to transplants at that time, and opened the door for further transplantation milestones.

In 1959, using sublethal total body irradiation to suppress the patient’s immune system successfully for the first time, the first kidney transplant took place between non-identical (fraternal) twin siblings (  In the following year, the first successful non-twin sibling kidney transplant was undertaken, while in 1961, the first kidney transplant between non-siblings was recorded.

To round this off, a different barrier was breached in 1962 when the first successful kidney transplantation from a deceased donor occurred.  Another milestone was reached with this procedure, as the immunosuppressive drug Azathioprine, now sold under the brand name Imuran, was first utilized.

Until later.

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Topic for Saturday, January 27th posting – Transplantation Firsts, Part 2 – First Liver Transplants

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Our CF Matters Hawaii – The Background of UNOS (United Network for Organ Sharing)

The Background of UNOS (United Network for Organ Sharing)

The system of organ donation early in the era of transplantation was focused on local networks.  The receipt of available organs was limited to those in an area hospital’s network.  As the process of organ transplantation became more advanced, and subsequently more of an option for those in need of life saving treatments, the necessity for a system to effectively track organ donors with recipients became necessary.  UNOS (United Network for Organ Sharing) fulfills that need.

The Southeastern Regional Organ Procurement Program was established as a kidney-sharing system in 1969 to increase the efficiency of organ placement (  Later named the Southeastern Organ Procurement Foundation, it became the central depository for data regarding all types of solid organ transplantation in 1977, with the establishment of a computerized database that housed that information.  That database was called UNOS.  Due to more transplantation resources become available, the U.S. Congress passed the National Organ Transplant Act in 1984, which began the Organ Procurement and Transplantation Network (OPTN) to maintain a national registry for organ matching (  UNOS was awarded the contract in 1986 to develop the OPTN, and has operated that network ever since.

In maintaining OPTN, UNOS manages the national transplant waiting list for the United States.  This organ sharing system maximizes the efficient use of deceased organs through equitable and timely allocation.  UNOS also collects, stores, analyzes and publishes data pertaining to every transplant event that occurs in the U.S. (

To support the organization and its efforts to organize and maintain the organ transplant network nationwide, UNOS bases its operations on three tenents: Education, Technology, and Policy.

For patients who need, or have received, transplants, UNOS fills those individuals’ quest for knowledge through education via the Transplant Living website ( which offers information about living donations, patient brochures that enable the public to understand the organ transplant process, and education to assist and inform transplant professionals of industry matters.

Technology is an integral component to maintain the nation’s organ transplant network.  UNOS’ electronic network, UNet, provides the vehicle for transplant professionals to register candidates onto the national network, and match them with donor organs as they become available.  In addition, the matching process is enhanced with the application, DonorNet.  While UNet enables candidate registration and matching, DonorNet increases efficiency within the system, as it records information about donor offers, and transmits it to transplant hospitals with compatible transplant candidates.

Finally, policy development that UNOS undertakes can be seen as the underpinning to its operations.  A 42-member Board of Directors addresses issues and develops solutions for matters involving patient and donor family issues, medical issues specific to various transplantable organs, and technical aspects of organ recovery and matching.  Further, ethical principles unique to the industry are identified, discussed and addressed.  Once issues are identified, proposals are drafted, and feedback is received.  Subsequently, the Board of Directors vote on the proposals, and if passed, policies and changes are implemented and communicated to the transplant community.

Until later.

If you would like me to research and post any topic of interest regarding Organ Transplantation, please feel free to e-mail your suggestions to me at I will do my best to place your idea into my queue of topics to cover on this site. Thanks for your feedback.

Topic for Saturday, January 20th posting – Transplantation Firsts, Part 1 – First Kidney Transplants

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Brief Overview of the History of Organ Transplantation

Throughout history, society has been intrigued by the prospect of extracting an organ, whether it be from a person or from an animal, and successfully transferring it to another.  This has been documented in Greek, Roman, and Chinese cultures.  Such an example is found in Homer’s The Odyssey, where a creature was created through the weaving together of body parts of a goat, lion, and dragon (  However, it wasn’t until the mid-20th century that this transplant process began to advance.

Until that point, organ transplants were advanced to the degree that the procedures would come up just short of success, with many failures due to organ rejection.  Examples range from an Italian surgeon in the 16th Century, Gasparo Tagliacozzi, who reconstructed noses and ears using skin from patients’ arms, to the transplant of the first human kidney using an organ from a deceased donor, performed by Ukrainian doctor Yu Yu Voronoy in 1936 (  The development of immunosuppressive drugs in the 1960s, together with tissue typing, became early tools to begin the advance of organ transplantation to where it is today.

As the medical technology and techniques improved, organ transplants become more successful and were being performed more frequently.  Due to the greater acceptance and usage of this practice, in the 1980s organizations were established to support the growth and coordination of transplantation.  United Network for Organ Sharing (UNOS) was incorporated to support the efforts of donation and transplantation professionals in 1984 (  Soon thereafter in 1986, UNOS was awarded a national Organ Procurement and Transplantation Network (OPTN) contract by the U.S. Department of Health and Human Services.  As part of UNOS’ mission, under that contract, UNOS has, and continues to:

  • Establish an organ sharing system that maximizes the efficient use of deceased organs through equitable and timely allocation
  • Establish a system to collect, store, analyze and publish data pertaining to the patient waiting list, organ matching, and transplants
  • Inform, consult and guide persons and organizations concerned with human organ transplantation to increase the number of organs available for transplantation.

Until later.


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Topic for Saturday, January 13th posting – The Background of UNOS (United Network for Organ Sharing)

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Cystic Fibrosis Gene CTFR. What is it?

Hi all,

The past two postings have mentioned the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene.

Some mutations to the CFTR causes CF, and CFTR is indeed the primary cause of Cystic Fibrosis. To allow a better understanding of this important root of Cystic Fibrosis, today’s post focuses on this CF gene.

The CFTR gene was identified in 1989 by geneticist Lap-Chee Tsui and his research team. Everyone has two copies of this gene, one from each parent ( Children who inherit a faulty CFTR gene from each parent will have CF. However; those who inherit a faulty CFTR gene from one parent and a normal CFTR gene from the other parent usually have no symptoms of cystic fibrosis, as they will have enough normal copies of the gene to be healthy (

Breaking down the acronym CFTR provides a glimpse of how it operates. ( –

Cystic Fibrosis – the disease that occurs when two copies of the gene do not function properly
Transmembrane – the prefix “trans” means “across” , so transmembrane means across the membrane (CFTR is a transporter gene)
Conductance – the ease with which electricity, gas, or fluid flows through a substance
Regulator – a mechanism of control

To go into further detail about CFTR, it is part of a family of genes that regulate the energy transfer which enables a cell to open and close its ion channels, and is located on the human chromosome 7. The CFTR gene produces the CFTR protein, which regulates the chloride ion content of certain cells in the body. When chloride ions are not able to leave the cells properly, as is the case with CF patients, water is retained in the cells, and as a result, some fluids, including mucus, are thicker than they should be.

A functioning CFTR gene is critical to normal human development, and mutations to this gene are life threatening in most cases, because they compromise the function of the pancreas, gastrointestinal tract, and respiratory systems. When the respiratory system is compromised, mucus build-up in the lungs result in infections. As for the related dysfunction of the pancreas and gastrointestinal tract, the results are the likely destruction of the pancreatic exocrine function and lack of proper absorption of nutrients (

Live life.

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BTW – If you would like me to research and post any topic of interest regarding Cystic Fibrosis, please feel free to e-mail your suggestions to me at I will do my best to place your idea into my queue of topics to cover on this site. Thanks for your feedback.


Topic for the next posting – Early Study of CF Medication Formulation CTP-656 Shows Superior Effects Compared to Existing CF Medication Kalydeco

Cystic Fibrosis Gene Mutation DF508. What is it?

Hi all,

As many in the cystic fibrosis community are aware, the new, breakthrough CF medication Orkambi is only approved for those patients who have two copies of the cystic fibrosis gene mutation Delta F508 (Double DF508). But what really is this particular gene mutation? That is the topic of today’s posting.

There are over 1,500 mutations that have been identified on the gene CFTR (Cystic Fibrosis Transmembrane Conductance Regulator). According to the website, only approximately 20 mutations of those 1,500 mutations occur commonly in the Caucasian population ( DF508 is just one of those mutations, and is caused by a deletion of the three nucleotides that comprise the codon for phenylalanine (f) at position 508.

DF508 is the most frequently identified CF gene mutation throughout the world. As a point of reference, an estimate of those with CF who carry DF508 on a worldwide basis is said to be at 75% (

DF508 is a mutant CFTR protein which cannot be folded into its proper shape when produced. The quality control mechanisms within the cell destroy this abnormal protein before it can reach the cell surface where its major normal function is to act as a channel through which chloride ions can pass in and out of the cell ( On the other hand, a correctly formed CFTR protein opens channels in the cell membranes that releases chloride ions out of cells, which causes osmosis to draw water out of the cells (

In fact, part of the way that Orkambi works successfully is by one of its combinations assisting to move the defective CFTR protein to its proper place at the cell surface. As well, another combination of Orkambi increases the activity of that protein once it is there, supporting the flow of salt and fluids, which helps thin the thick mucus that builds up in the lungs and other organs (

Scientists have estimated that the DF508 mutation occurred over 52,000 years ago in Northern Europe. A hypothesis that supports the evolvement of this mutation is that it causes a positive effect by reducing water loss, since DF508 inherently does not allow the release of water from the cells, during cholera, which was a common cause of death in Europe when the mutation first appeared (

Please check out the introduction of this posting at Youtube at

NEXT POST to Our CF Matters Hawaii, September 26th – “Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). What is it?”


FDA Approves Cystic Fibrosis Medication ORKAMBI – July 2, 2015

Hi All,

On July 2, 2015, the FDA approved the break through Cystic Fibrosis drug Orkambi (  This CF drug, which is produced by Vertex Pharmaceuticals, together with an earlier developed CF medication, Kalydeco, are the first medications to try and counteract the underlying genetic defect that causes the disease, as opposed to only treating symptoms of this disease, as historic medications have done.

Approximately 30,000 Americans have CF, which is characterized by the buildup of sticky mucus in the lungs, causing frequent infections and a gradual decline in lung function.  Orkambi has been approved for those cystics who have two copies of the CF gene mutation F508del, of which about half of those 30,000 individuals hold these two mutations.   Of that subset, Orkambi has been approved for around 8,500 individuals aged 12 and older.

Orkambi’s approval was based on data from two double blinded, placebo controlled Phase 3 studies (TRAFFIC and TRANSPORT).  Results of those studies experienced statistically significant improvements in lung function, as well as decreases in pulmonary exacerbations (IV and/or hospital treatments) and improvements in Body Mass Index (BMI).

Orkambi combines lumacaftor and ivacaftor to treat these problems with a two-step approach. Lumacaftor helps move the defective CFTR protein to its proper place at the cell surface. Ivacaftor increases the activity of the protein once it is there, supporting the flow of salt and fluids, which helps thin the thick mucus that builds up in the lungs of people with Cystic Fibrosis ( ).

As stated above, at this point, Orkambi has been approved only for those CF patients with two copies of the F508del.  F508del is a deletion mutation on the cystic fibrosis transmembrane conductance regulator or CFTR protein which causes abnormal transport of sodium through membranes, leading to inflammation and mucus deposition in the lungs of patients ( /).

Orkambi is taken as a dose of two tablets every 12 hours (morning and evening) with fat-containing foods.

Please see the video introduction of this topic at YouTube –


NEXT POST to Our CF Matters Hawaii, September 19th – “Cystic Fibrosis gene mutation F508del.  What is it?”

RE-POST – Final Data: Phase 2 Combo Study VX-809 & Cystic Fibrosis Drug Kalydeco – 2012 North American CF Conference



Hi all,

Earlier this month at the at the 26th Annual North American CF Conference, final data from a Phase 2 study of a trial involving a treatment with the CF drug compound VX-809 and Kalydeco was discussed by Dr. Michael Boyle of Johns Hopkins School of Medicine. Overall, Dr. Boyle stated that the final results showed statistically significant improvements in lung function for cystic fibrosis patients treated with this potential drug.

The final results from this trial that enrolled 109 people with CF aged 18 years and older with one or two copies of DF508 were based on the last 28 days of the 56-day study were initially released this past June by the manufacturer of Kalydeco, Vertex Pharmaceuticals, Inc. ( Participants were divided into five treatment groups of approximately 20 individuals each. Three groups of those with two copies of DF508 received the experimental drug VX-809 alone for 28 days, then in combination with Kalydeco for an additional 28 days. A group with one copy of DF508 followed the same regime. A placebo group holding both one and two copies of the mutation was also involved in this trial.

The three groups with members who had two copies of DF508, the most common cystic fibrosis gene mutation, were treated with varying doses of VX-809 (200mg, 400mg, 600mg) in combination with Kalydeco. One of the primary endpoints to this study focused on the improvement of lung function, defined as the percent predicted FEV1 (the amount of oxygen that can be forcibly exhaled in one second). These final results showed that the most significant improvement was found with those who received 600mg of VX-809. To quantify this, from day 28 to 56, when patients began to receive Kalydeco in addition to VX-809, as opposed to the first 28 days when the group was dosed only with VX-809, it was revealed that 55% of participants witnessed a greater than 5% improvement in FEV1. Further, from day 28 to 56, 25% of the 600mg group showed a 10% improvement in FEV1.

Patients in this study who hold just one of copy of DF508 also responded positively with VX-809, albeit at a lower success rate than individuals who had two copies of DF508. Based on this information, Vertex is planning additional studies of VX-809 and Kalydeco for people with just one copy of the mutation.

Another primary endpoint of this study was to determine the improvement of sweat chloride in the study population. A reduction of sweat chloride shows that this drug combination is likely causing a positive change in the function of the CFTR protein. An improper function of the CFTR is the known cause of CF, which would mean that a reduction in the chloride certifies that the medication is performing as expected, and is treating the underlying cause of CF. However, although improvements were shown for participants who had two copies of DF508 during the first 28 days of this study, results from the final 28 study days found no statistically significant reduction of sweat chloride.

Per the website, the success of this drug combination could boost the eligible pool of individuals with CF by up to ten times ( In early 2013, Vertex plans to begin a type of trial on Kalydeco and VX-809 on the CF population with two DF508 mutations that is designed to provide the U.S. Food and Drug Administration, and similar authorities in other countries, with data to decide whether or not to approve this potential drug (
A slideshow of Dr. Boyle’s presentation can be found at

Live life.

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BTW – If you would like me to research and post any topic of interest regarding Cystic Fibrosis, please feel free to e-mail your suggestions to me at I will do my best to place your idea into my queue of topics to cover on this site. Thanks for your feedback.