The month of April has provided encouraging news for those afflicted with cystic fibrosis (CF).
Vertex Pharmaceuticals announced that its CF transmembrane conductance regulator (CFTR) dual combination tezacaftor with ivacaftor therapy successfully met its primary endpoints in two of its Phase III trials.
Anthera Pharmaceuticals also announced that its pancreatic enzyme replacement therapy (PERT) Sollpura, for CF patients with exocrine pancreatic insufficiency (EPI), matched the efficacy of Pancreaze (pancrelipase).
In addition, the FDA and Health Canada recently gave Laurent Pharmaceuticals the green light to start a Phase II clinical trial for its novel anti-inflammatory drug LAU-7b.
This news marks significant progress being made in the CF therapeutic industry.
CF is an inherited, autosomal recessive disorder that causes persistent lung infections and impairs breathing ability over time, and affects more than 70,000 people worldwide.
Characterized by a loss of function in the CFTR protein, CF causes abnormally thick, sticky mucus production that can lead to airway obstruction and lung infections, and can eventually lead to pancreatic insufficiencies due to mucous blockage of the pancreatic duct.
There are currently four classes of approved treatments for the CF indication: inhaled antibiotics, mucolytics, CFTR modulators, and PERTs.
During the last five years, Vertex Pharmaceuticals has dominated the CFTR modulator space with its marketed drugs Kalydeco (ivacaftor) and Orkambi (ivacaftor/lumacaftor). CFTR modulators are drugs designed to correct the function of defective CFTR protein translated from a mutated CF gene.
To further tighten its grasp over the CFTR market, Vertex recently announced its purchase of Concert Pharmaceuticals’ Phase II pipeline CFTR modulator therapy CTP-656, which is a deuterated form of ivacaftor.
In addition, Vertex Pharmaceuticals’ Phase III EVOLVE and EXPAND studies of dual combination therapy tezacaftor with ivacaftor showed statistically significant improvements in lung function in people with CF ages 12 and older.
The EVOLVE study evaluated the combination treatment in people who have two copies of the F508del mutation. This study met its primary endpoint with a mean absolute improvement in ppFEV1 through 24 weeks of 4.0 percentage points from baseline compared to placebo (p < 0.0001).
The EXPAND study evaluated the combination treatment in patients who have one mutation that results in residual CFTR function and one F508del mutation. This study met the primary endpoints of absolute change in ppFEV1 from baseline to the average of the Week 4 and Week 8 measurements, with the tezacaftor/ivacaftor combination treatment demonstrating a mean absolute improvement of 6.8 percentage points compared to placebo (p < 0.0001), and the ivacaftor monotherapy group demonstrating a mean absolute improvement of 4.7 percentage points compared to placebo (p < 0.0001).
These results have Vertex poised to bring yet another blockbuster CFTR modulator therapy to market.
Vertex plans to submit a New Drug Application to the FDA and a Marketing Authorization Application to the EMA for its tezacaftor with ivacaftor combination in Q3 of 2017.
The PERT class indicated for CF patients has been dominated by many different pancrelipases, such as AbbVie’s Creon, Digestive Care’s Pertzye, J&J’s Pancreaze, and Aptalis’ Zenpep.
All of these products are a combination of pancreatic porcine-derived lipases, proteases, and amylases indicated for the treatment of exocrine pancreatic insufficiency due to CF.
Anthera Pharmaceuticals’ Sollpura (liprotamase) can potentially become the first non-porcine-derived PERT indicated for CF patients, offering CF patients an alternative if they don’t react well to its porcine-derived counterparts.
Anthera announced positive results from its SOLUTION study, indicating that the company observed continued tolerability and maintenance of weight and height in all of the Sollpura-treated CF patients with EPI during an Extension Period. Sollpura matched the efficacy of Digestive Care’s Pancreaze.
Similar increases in height and decreases in body mass index (BMI) were observed in patients who were administered Sollpura and patients who were administered Pancreaze. Anthera plans to begin another Phase III trial, RESULT, in mid-2017. If approved, Sollpura would join an already crowded market of PERTs indicated for CF patients.
There are currently no anti-inflammatory drugs indicated for CF, making the approval of the trial design for Laurent Pharmaceuticals’ Phase II APPLAUD study all the more significant.
The trial plans to investigate LAU-7b’s efficacy and safety on the preservation of lung function in CF patients. Laurent will receive support from Cystic Fibrosis Canada and a $3m development award from the US Cystic Fibrosis Foundation.
If approved, LAU-7b would be the first anti-inflammatory drug indicated for CF that activates the resolution phase of inflammation.