An Undeniable Hope Part 2: An Accumulation of Steps Led To Orkambi

This past Saturday, Fedex brought a small unassuming box to the porch of my home. It didn’t take me long to open it and find Vertex’s newest drug, Orkambi, wrapped in its white and lime green colored box. Inside lay foil wrapped pills neatly labelled Sunday through Monday to be taken each morning and night.

Although the drug was only recently approved by the Food and Drug Administration (FDA) on July 2, I have been waiting for its arrival well over two years when I first learned of its progress through clinical trials. The drug represents a shift in the treatment of nearly half of those with CF, who for the first time can take a drug that takes the disease head on by beginning to correct the function of the defective protein, rather than only extinguishing flaring symptoms of the disease.

This new approach has brought an undeniable hope to the CF community and as Orkambi sits fresh on my counter I wait to see what benefits it may bring to my health, not just in the coming weeks, but over an unknown number of years. I have long held onto the words ‘dum spiro spero’ — while I breathe I hope — and I can only hope that my breathe will continue to grow stronger with Orkambi.

This drug is a victory of science and advocacy, but it was not achieved spontaneously in a vacuum. It is the crescendo of an accumulation of steps that churned slowly over the past century in science and medicine that led to its inception.

The cornerstone of this achievement came in 1938 when cystic fibrosis was first described and documented by Dorothy Anderson, M.D., a graduate of Johns Hopkins University School of Medicine. Anderson was a pioneer and maverick in the medical field and the National Institutes of Health (NIH) in Celebrating America’s Women Physician’s tell how, “Dr. Anderson considered herself a rugged individualist, a pediatric clinician, a research chemist, and a roofer and carpenter happy to make her own home improvements.”

Anderson happened upon the disease during an autopsy of a child with celiac disease in which she “noticed a lesion in the pancreas.” Further investigation led her to identify the disease and even develop a diagnostic test which is still in use today. Her initial discovery was seminal in identifying the disease that was and still is responsible for taking far too many number of lives, particularly those of children. It was in her description of cystic fibrosis that gave a name and a face to the antagonist that researchers and doctors then set out to conquer.

RELATED:  FDA Approves ORKAMBI, New Cystic Fibrosis Combination Drug

In the middle of the twentieth century, CF was largely uncontrollable, with physicians and families helpless to intervene as the disease followed its fatal course. In the 1950s, children often died early in childhood even before beginning primary school.

It wasn’t until 1989 that the mystery of the disease began to unravel as Lap-Chee Tsui, at the Hospital for Sick Children in Toronto, Canada, and colleagues identified the cystic fibrosis transmembrane conductance regulator (CFTR) gene responsible for the disease. This discovery opened the field of CF research to allow scientists to begin to look at the disease at a cellular level to understand what steps needed to be taken to develop drugs that could effectively counter-act the disease.

Only four years later in 1993, Pulmozyme (dornase alfa) developed by Genentech was approved by the FDA. The median age of survival at that time had risen to 29 years of age and Pulmozyme, a mucolytic used to cut DNA in the sputum, had shown improvements in patient’s symptoms and lung function in clinical testing.

Then in 1997 Tobi was reformulated and approved by the FDA for inhalation to help with chronic infection against the devastating bacteria, Pseudomonas aeruginosa. This allowed patients to combat chronic pseudomonal infections, which until that time could be treated only through IVs. Trials had demonstrated that use of the inhaled Tobi helped to improve lung function as well as decrease levels of the bacteria in sputum.

A third medication came in 2004 called hypertonic saline and was quickly added to the core regime of CF treatment. The drug was developed from an Australian study in which doctors noticed better lung function in those with CF who surfed and were consistently exposed to the misty salt water. The drug helps ion balance outside cells to draw water out to increase the level of the airway surface liquid used by cells to clear mucous from the lungs.

In 2012 a paradigm shift was brought to the treatment of CF with the approval Kayldeco by Vertex. The drugs approved before this time although beneficial to patients only mitigated symptoms of the disease without addressing its cause. Kayldeco, initially approved for those with the G551D mutation, was the first drug to directly interact with the defective protein in CF to restore its normal function. The success of Kayldeco then paved the way for continued development of other CFTR modulators such as VX-809 and VX-661.

The year following the release of Kayldeco in 2013 the CF Foundation patient registry report noted that the median age of survival of someone with CF had increased to 40.7 years, a gain of 11.7 years since 1993. The number 40.7 is powerful to consider. It did not come spontaneously, or even quickly, but those years were gained with an ever growing accumulation of steps as drugs such as pulmozyme, tobi, hypertonic saline and kalydeco were moved into the hands of patients. Their success, through the work of researchers, families and those in the CF Foundation provided an avenue through which we can now celebrate our newest success in the approval of Orkambi.

The number, 40.7, is the new beginning of the story as the white and lime-green colored box of Orkambi sits on the counter in my kitchen. I am at the age of 26 as the result of pulmozyme, tobi, and hypertonic saline before it and now I begin the next step as I close my eyes and slip the two pink pills into my mouth watching the number climb from 40.7 to wherever it may land next. Today the words ‘Dum Spiro Spero’ sit well — while I breathe I hope.