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Alan Franciscus
HCV Advocate
HBV Advocate

Wednesday, April 16, 2014

New England Journal of Medicine - Gilead, by Alan Franciscus (epub ahead of print)

  —Alan Franciscus, Editor-in-Chief

There were two journal articles about the all oral combination therapy being developed by Gilead that were recently published in the New England Journal of Medicine (NEJM).  The articles reported on Phase 3 clinical trial results for the treatment of chronic HCV genotype 1a and 1b in patients who were treatment naïve and treatment experienced. 

There were three medications used in the study:
  • Sovaldi (sofosbuvir) – polymerase inhibitor, 400 mg
  • Ledipasvir – NS5A inhibitor, 90 mg
  • Ribavirin – dosed twice a day based on body weight
Note:  Sofosbuvir and ledipasvir are coformulated into one pill, taken once a day.  Ribavirin is dosed twice a day. 

#1. Treatment Naïve:  ION-1

Patient Population:   
A total of 865 treatment-naïve patients were treated with ledipasvir and sofosbuvir with and without ribavirin.  There were 4 treatment arms—2 arms in the 12-week groups and 2 arms in the 24-week treatment groups.   The patient population across all of the treatment arms weas similar:  Male 55 - 64 yo, mean age 52% - 53%, white 82% - 87%, genotype 1a (66% - 68%), genotype 1b (31% - 33%), and cirrhosis (15% - 17%). 

The overall cure rates were 97% to 99%.  The cure rates are listed below by drug combinations and treatment duration.   

12-week Regimen
Cure Rates
24-week Regimen
Cure Rates
99% (211 of 214 pts)
98% (212 out of 217 pts)
97% (211 of 217 pts)
99% (215 of 217 pts)
*Ledipasvir (LDV); Sofosbuvir (SOF); Ribavirin (RBV)
Side effects:
The most common side effects were fatigue, headache, insomnia, and nausea.   There were no treatment discontinuations. 

This combination without ribavirin for 12 weeks works very well in HCV genotype 1 treatment-naïve patients.   
#2. Retreatment—ION-2: 

Patient Population:
There were a total of 440 treatment-experienced patients who were treated with the combination of ledipasvir and sofosbuvir with and without ribavirin.  There were 4 arms—2 arms in the 12 week groups and 2 arms in the 24 week groups. The patient population was similar across all treatment arms:  male (68% - 75%), age (~55 - 57 yo), white (77% - 85%), genotype 1a (78% - 79%), genotype 1b (21% - 22%), and cirrhosis (20% in all treatment arms).

The types of prior non-response—relapse or breakthrough, non-response to pegylated interferon, ribavirin therapy with and without protease inhibitor therapy—were similar between all arms. 

The cure rates across all arms were very high—94 to 99% regardless of type of prior response.  The results are listed below by drug combination and treatment duration.  

12-week Regimen
Cure Rates
24-week Regimen
Cure Rates
94% (102 out of 109 pts)
99% (108 out of 109 pts)
96% (107 of 111 pts)
99% (110 of 111 pts)
*Ledipasvir (LDV); Sofosbuvir (SOF); Ribavirin (RBV)
Side Effects:
The most common side effects were fatigue, headache and nausea.  There were no treatment discontinuations due to side effects. 

The combination of ledipasvir and sofosbuvir continues to shine.  Based on these results it appears that the combination of ledipasvir and sofosbuvir for 12 weeks without the use of ribavirin is effective in HCV genotype 1 treatment-experienced patients—it’s hard to imagine a once-a-day pill for 12 weeks with minimal side effects.   But imagining this is difficult when you consider the high cost of sofosbuvir even without the addition of ledipasvir and the problems many people face with access to care or insurance that doesn’t provide any or enough coverage.     

UK: NHS England agrees funding for life-saving hepatitis C drug Sofosbuvir

NHS England has approved an £18.7 million investment in a new drug for the treatment of hepatitis C.

Around 500 patients with acute liver failure, and/or awaiting liver transplantation, are expected to benefit from the decision to fund Sofosbuvir.

The hepatitis C virus causes inflammation of the liver, affecting its ability to function. Whilst many sufferers naturally clear their infections within six months, others develop chronic hepatitis which is usually life-long without therapy.

Patients with severe telaprevir-related skin eruption can continue treatment

Patients with grade 3 widespread morbilliform eruption associated with telaprevir can continue their triple therapy as long as they are closely monitored, according to researchers from Massachusetts General Hospital.
“With proper monitoring, it appears that patients with a grade 2 (moderate) telaprevir eruption or uncomplicated grade 3 (severe) telaprevir eruption can safely be treated symptomatically without the need for discontinuation of triple therapy,” the researchers wrote in JAMA Dermatology. “Given that triple therapy is often the last therapeutic option for patients with [hepatitis C virus], further research to examine this novel approach should be conducted prospectively.”

Eight patients with a grade 3 morbilliform eruption related to telaprevir (Incivek, Vertex) were evaluated by dermatologists a mean of 13.3 days after symptom onset. All of the patients had an eruption that covered more than half of their total body surface area, which developed a mean of 20.1 days after initiating treatment. The trunk and extremities were affected in all patients, and none had eosinophilia or liver function test results indicating systemic involvement.

Read more....

Senate panel takes up medical registry bill

CONCORD, N.H. (AP) — Other states are eager to follow New Hampshire's lead in monitoring medical technicians like the one who stole drugs from Exeter Hospital and infected patients with hepatitis C, but the state can still do more to prevent future problems, according to a lawmaker who is planning additional legislation.

Rep. Tom Sherman told a Senate committee Wednesday that he hopes to file another bill next session to complement two the House already has passed in response to David Kwiatkowski. Kwiatkowski is serving 39 years in prison for stealing painkillers and replacing them with saline-filled syringes tainted with his blood.

One bill currently before the Senate would require health care facilities to develop and implement drug-free workplace policies and to test employees for drugs if there is a reasonable suspicion of drug use. The other, which had a public hearing Wednesday, would create a board to register health care workers who are not otherwise already licensed or registered and who have access to both drugs and patients. Hospitals would be required to report disciplinary actions to the board, which could perform its own investigations of wrongdoing.

Read more....

Staying Safe Intervention reduced HCV, HIV risk in drug users

The Staying Safe Intervention program reduced risk factors for contracting hepatitis C virus infection and HIV among people who inject drugs, according to recent study data.
Researchers from New York University’s Center for Drug Use and HIV Research created the intervention program based on a 2005 study that examined behaviors and strategies of people who injected drugs (PWID) for 8 to 15 years without contracting hepatitis C virus (HCV) infection or HIV. Methods of those drug users were used to teach PWID strategies during five group sessions on how to reduce injection-related risk behavior and risks for HCV and HIV, and how to develop planning and management skills.

Sixty-eight PWID participated in the intervention; 87% attended at least one group session, and 46% attended all five.


UK: Needle exchange scheme numbers rise 50% in four years

The number of needles issued by an exchange scheme in Northern Ireland has risen by more than 50% in the past four years.

The Public Health Agency (PHA) coordinated project gives out needles and syringes to people who are injecting intravenous drugs, such as heroin or steroids.

In 2012, 21,220 visits were made to the scheme with 213,295 needles handed out.

The scheme has been in operation since 2005.


Louisiana Taking Away Medicaid Lifeline for Disabled, Other Vulnerable Residents

Two years ago, Donna Risso and her friend Michael were living under a bridge in New Orleans. They were struggling not only with homelessness, but also with Donna's mounting health problems, which included hepatitis C, cirrhosis of the liver, encephalitis, pancreatitis and chronic anemia. Donna was a "frequent flyer" at the emergency room, often five to 10 times a month, but her health was getting steadily worse.

Social workers using federal and state resources helped Donna find housing and got her on a state program called "disability Medicaid," which covers health care costs for people who meet federal disability criteria but are not yet on the federal program. This important initiative, common in many states, is a bridge to health services for people applying for federal benefits, which can take years.

Although the program was a lifesaver for Donna, Gov. Bobby Jindal terminated "disability Medicaid" in Louisiana as of Jan. 1, leaving 9,200 people across the state with no coverage.

Read more....