FVII Gene Therapy Trial in Dogs; New FIX and HCV Drugs

Author: Sarah M. Aldridge, MS

FVII gene therapy trial update

Patients with factor VII (FVII) deficiency share your pain. Like hemophilia A and B, they experience joint and muscle bleeds, bruising and bleeding after surgery. Many babies are diagnosed after a life-threatening bleed in the gastrointestinal tract or brain during their first 6 months of life. There is an approved recombinant clotting factor they can use to treat bleeds, but it doesn’t stay in the bloodstream long and is expensive.

A study published in the December 23, 2015, online issue of Blood showed that a gene therapy trial in dogs was successful, bringing hope for FVII patients. Researchers at the Children’s Hospital of Philadelphia (CHOP) and the University of North Carolina at Chapel Hill injected one dose of a genetically engineered FVII gene into dogs using an adeno-associated virus (AAV). The AAV is the transport system to sneak the modified genes into the body in a way that the immune system won’t recognize as foreign. 

The dogs used in the study come from a colony at UNC-Chapel Hill. Not only did they have FVII deficiency, but their mutation was the same as that in the majority of humans. The dogs maintained therapeutic levels of FVII,  one for as long as three years. 

“Our data are the first to demonstrate feasibility, safety, and long-term duration of AAV gene therapy for factor VII deficiency,” said Paris Margaritis, DPhil, lead investigator and hematology researcher at CHOP in a UNC-Chapel Hill press release. “The table is now set to propose clinical trials that would treat people who suffer from this disease.”

New drugs for you

Factor concentrates that last longer in the bloodstream may mean you can put more space between infusions. That’s the goal for CSL Behring’s Idelvion® for hemophilia B, or factor IX (FIX) deficiency. By linking the FIX protein to albumin, a blood protein, the factor product circulates longer. According to the company, it is the first and only coagulation FIX recombinant albumin fusion protein to treat hemophilia B.

In the PROLONG-9FP clinical trial, 90 subjects ranging in age from 1 to 61 were tested. They all had FIX levels less than or equal to 2%. Those in the prophylaxis arm showed annualized bleeding rates of 0. Their FIX levels measured greater than 5%, transforming them from severe to mild hemophilia. Patients in the on-demand arm controlled 94% of bleeds with 1 infusion; 99% of bleeds required 1-2 infusions. The most prevalent side effect was  headache.

Idelvion is approved for prophylaxis, on-demand treatment and perioperative bleeding for children and adults. The manufacturer says that with this long-acting recombinant FIX therapy, some patients 12 and older may be able to stretch the time between infusions to up to 14 days. 

In January 2016, a new oral hepatitis C virus (HCV) drug was approved by the FDA. Merck’s Zepatier™ is for patients with chronic HCV infection, genotypes 1 and 4. It contains elbasvir, an NS5A replication complex inhibitor, and grazoprevir, an NS3/4A protease inhibitor. Some patients will take it with ribavirin.

The clinical trials for Zepatier were conducted for 12 or 16 weeks on 1,371 subjects. Some had failed previous trials, others had compensated cirrhosis and HIV-1 co-infection. Still others had severe kidney damage and were on dialysis. The drug was highly effective in providing sustained viral response (SVR), a “cure,” 12 weeks after treatment ended. SVR rates were 94% to 97% for those with HCV-1 and 97% to 100% for HCV-4. 

Side effects included anemia, headache, fatigue and nausea. The label will warn about the possibility of elevated liver enzymes. Zepatier is not recommended for people with moderate to severe liver impairment.