New Disease-Modifying, Personalized Cystic Fibrosis Treatment, Starting a Trend in Drug Development

Wednesday 15 May 2013, Amsterdam

Disease-modifying  treatments  are  becoming  a  reality  for  Cystic  Fibrosis  (CF)  sufferers,  potentially transforming this life-threatening condition into a manageable one, according to new analysis by research and consulting our team.

The new report highlights Vertex Pharmaceuticals’ Kalydeco (ivacaftor), which received Marketing Authorization Approvals (MAA) in the US and EU last year, and represents a milestone in the CF therapeutics market, as we begin to enter an era of personalized medicine.

CF is caused by a genetic mutation which leads to the production of thickened sticky secretions in organs with epithelial cell linings, including the respiratory tract. Over time, lung infections lead to airway destruction,  respiratory  failure  and  death.  The  first-in-class  CFTR  modulator  Kalydeco,  a  CFTR potentiator works to restore the function of the mutated CFTR protein in patients with the G551D gating mutation of CF, allowing an improved  flow of salt and fluids on the surface of the lungs.

Only around 4% of CF patients in the US have the G551D gating mutation, and more studies are needed to help determine whether people with other CF gating mutations might also be eligible for Kalydeco. Still, the drug’s approval has paved the way for a new class of therapies, which offer a personalized treatment approach to patients and could be highly profitable for its developers.

Vertex is now developing a combination therapy of potential first-in-class CFTR modulator lumacaftor (VX-809) with Kalydeco (VX-770) for the treatment of CF patients who are homozygous for the F508del mutation in the CFTR gene. The CFTR corrector, lumacaftor increases trafficking of the defective CFTR protein to the cell membrane, where it can exert its functions. The combination therapy is currently in Phase III stage of development, and is expected to gain approval in 2014.

It is estimated that around half of all CF patients are homozygous to the F508del mutation, and Vertex has also announced plans to explore the lumacaftor/Kalydeco combination therapy in patients that are heterozygous to the F508del mutation – a condition that is thought to apply to 75%–80% of all CF patients. This means that the combination therapy could potentially be used by the vast majority of CF patients in the future. Vertex’s goal to offer treatment to as many CF patients as possible is also backed by the development of a new generation of CFTR correctors, which are currently in early stages of clinical development.

In addition, PTC Therapeutics is collaborating with Genzyme to enter the upcoming CFTR modulator market, with its pipeline drug ataluren which is currently in Phase III development for patients with nonsense mutations in the CFTR gene. This drug is designed to allow the protein synthesis machinery to ignore these nonsense mutations, potentially addressing the underlying cause of CF in this patient group. It is estimated that approximately 10% of all CF patients are carriers of nonsense mutations.

Regulatory authorities are supporting pharmaceutical development in this therapy area. Lumacaftor and Kalydeco are the first two drugs to be granted Breakthrough Therapy Designation by the FDA, and both drugs now have orphan drug status in the US and EU, giving them further regulatory support and market exclusivity for seven years in the US and 10 years in the EU. However, the high price of CFTR modulators may prevent reimbursement by local health authorities and insurance companies, hindering the market success of these new therapies.

We valued the CF therapeutics market across the US, France, Germany, Italy, Spain, and the UKat $1.2 billion in 2012, and is predicted to rise to $4.6 billion by 2017 at a rapid Compound Annual Growth Rate (CAGR) of 31.9%.