FDA Approves Orkambi to Treat Young Children with CF

Orkambi works for those with two copies of the F508del variant of the CFTR mutation – the most common mutation among patients with CF around the globe.

 FDA Approves Orkambi to Treat Young Children with CF

Orkambi is an oral drug developed by Vertex Pharmaceuticals and approved by the United States Food and Drug Administration (FDA) for the treatment of cystic fibrosis (CF) in certain patient groups. It is the second drug to be approved for use in patients with CF, after Kalydeco.

Orkambi is a combination of two therapeutic agents – ivacaftor and lumacaftor. Ivacaftor assists defective channels in functioning properly, while lumacaftor increases the quantity of proteins on cell surfaces. “The combination of these two things helps to keep a healthy balance of salt and water in the organs – particularly the lungs” explained The Cystic Fibrosis Trust.

Every individual inherits two copies of the CFTR gene, one from each parent. Orkambi works for those with two copies of the F508del variant of the CFTR mutation – the most common mutation among patients with CF around the globe.

Clinical Trials

Back in 2015, Orkambi was approved for patients with CF ages 12 and up, based on the outcomes of three Phase 3 clinical trials: TRAFFIC, TRANSPORT, and PROGRESS. The TRAFFIC and TRANSPORT clinical trials involved the participation of 1,108 patients with CF who had two copies of the F508del mutation. The researchers found that the patients who took either 400mg or 600mg of lumacaftor and 250mg of ivacaftor every morning, as well as another 250mg of ivacaftor at night for a period of 6 months experienced improved lung function, lower usage of antibiotics, and fewer hospitalizations. The patients were then invited to partake in the PROGRESS clinical trial, continuing on the same dosages as the initial two trials. Placebo groups (600 mg of lumacaftor and 250mg of ivacaftor every morning, as well as 250mg of ivacaftor at night) were also analyzed for two years. The PROGRESS clinical trial confirmed that the long-term use of Orkambi was safe and tolerable, as well as improved lung function and helped maintain patients’ body-mass index.

In 2016, FDA approval of Orkambi was expanded to include patients with CF ages 6-11 who had two copies of the F508del mutation. Two Phase 3 clinical trials took place with patients in this age group. In both trials, the patients were given 200mg of lumacaftor and 250mg of ivacaftor every 12 hours for a period of 6 months. Like the previous clinical trials, the outcomes revealed that Orkambi was safe and tolerable, as well as showed improvements in lung function.

Access extended to younger children with CF

Most recently, the FDA approved Orkambi for the treatment of patients with CF ages 2-5 who had two copies of the F508del mutation. “Cystic fibrosis is a systemic, multi-organ, progressive disease that is present from birth. Research suggests Orkambi could impact CF outcomes in patients as young as 2 years old. This approval is a significant development that enables physicians to begin treating the underlying cause of the disease in this population earlier than ever before” said John McNamara, medical director of the CF program at Children’s Minnesota Hospital.

The decision to approve Orkambi for this age group means that an additional 1,300 children with CF in the United States are qualified to receive the therapy. This brings the total number of children to benefit from the drug to around 12,300. “For the first time, children ages 2 through 5 who have the most common form of CF have a treatment for the underlying cause of their disease” said Reshma Kewalramani, executive vice president and chief medical officer of Vertex Pharmaceuticals. “We believe it is important to treat the underlying cause of the disease as early as possible and this approval is another significant milestone in our journey to bring effective medicines to all people living with CF” she added.

The approval of Orkambi for young children with CF ages 2-5 was granted based on outcomes from a Phase 3 clinical trial. The trial analyzed lumacaftor (100mg and 150mg doses) and ivacaftor (125mg and 188mg doses) given in 60 patients (ages 2-5) every 12 hours for a period of 6 months. The researchers found that the drug’s safety profile was similar in this particular age group as it was in children ages 6 and up. “This is great news for our community, as research indicates that starting treatment with CFTR modulators early may limit the onset of complications from the disease. We are committed to building on this momentum to help bring more and better treatments to the people with CF who need them” said Preston W. Campbell III, president and CEO of the Cystic Fibrosis Foundation.

The most common side effect experienced among the young patients was a cough, although 4 patients experienced more severe side effects (1 gastroenteritis, 1 constipation, and 2 pulmonary exacerbations) and 3 patients discontinued treatment due to elevated liver enzymes.

Vertex Pharmaceuticals has submitted a Marketing Authorization Application to the European Medicines Agency, with an aim to extend the use of Orkambi in children with CF ages 2-5. The application intends to made the drug available to children in Europe as well and the decision is expected in the first half of 2019.

The battle over price and long-term impact

Regardless of the benefits that Orkambi has to offer, patients face challenges in accessing this therapy, due to its high cost. The drug’s annual price is approximately $250,000 per patient. Now, the New York State’s Drug Utilization Review Board is taking a vote to demand that Vertex Pharmaceuticals (the manufacturer) lowers the annual price to $83,000 per patient.  

ther territories have also faced challenges with the high cost of Orkambi. In fact, the United Kingdom’s National Institute for Health and Care Excellence rejected the drug due to its high cost back in 2016. And despite negotiations to lower the annual price, no agreement has been reached.  

The National Health Service (NHS) has also demanded that Vertex Pharmaceuticals lower the annual price of Orkambi; however, they too have failed to come up with a mutual agreement. Vertex’s chief commercial offer, Stuart Arbuckle, commented on the matter, stating “If you look at the offer the NHS has made, essentially they are asking for a 90% discount for our current and future medicines compared to what the German government is paying for Orkambi, our approved medicine. We think that is a clear demonstration that the NHS is undervaluing the benefits these medicines can have for people living with cystic fibrosis.” For now, it appears as though Vertex pharmaceuticals holds leverage because the federal government requires the state to cover the costs associated with Orkambi. However, the state can limit its use, bringing forth a bigger battle over cost and long-term impact.