We are not opposed to pharmaceutical drugs – we just prefer natural answers, if available. As confident as we are in our natural Hepatitis protocol, we also feel obligated to let you know of some new cures coming out in 2014 or 2015. (“Cure” being defined as 24 weeks with no virus detection. The people who have relapses after that are not counted.) The side effects don’t seem to be excessively bad. The only detriment seems to be that the drugs will be very expensive.
(Excerpts from Ransdell Pierson & Bill Berkrot, (Reuters), and Simeon Bennett.)
The New Drugs
AbbVie Inc’s Aviator – ABT: 450r, 267 and 333.
Bristol-Myers Squibb – Daclatasvir
Gilead Sciences Inc. – Sofosbuvir
The traditional two-drug chemo-style treatments (ribavirin and interferon) ‘cure’ only about 40% of people. Until now, treatment for hepatitis C consisted of injections of interferon, a general immune stimulant that turns on the body’s defense mechanisms. However, at the high doses required, interferon often creates toxic side effects. Also, more than two-thirds of hepatitis C patients cannot use the regimen treatment.
The side effects are brutal, long-term and, in some cases, may be permanent. These side effects can include serious hemolytic anemia, worsening of cardiac disease, memory loss, weight loss, skin rashes, hair loss, muscle or bone pain, diarrhea, and vomiting. Ribavirin also causes birth defects, fetal demise, and also may be carcinogenic.
Hepatitis C affects an estimated 170 million people worldwide, and if left untreated can lead to cirrhosis, liver cancer or the need for a new liver. Existing treatments must be taken by patients for 6 months to a year. Several companies are working to eliminate infusions of difficult-to-tolerate interferon from the regimen, while raising cure rates and shortening the length of treatment.
AbbVie Inc’s Aviator Study
AbbVie Inc’s experimental hepatitis C treatment, in a short term study, cured up to 96 percent of patients in just 12 weeks – potentially a potent oral therapy for the serious liver disease. AbbVie’s treatment, a combination of five oral medications, is expected to be a close contender to a treatment in development by Gilead Sciences Inc.
The latest findings from an ongoing trial, called Aviator, sponsored by AbbVie, were unveiled at a meeting in Amsterdam. AbbVie said on Tuesday that about 88 percent of new patients with hepatitis C were deemed cured after only eight weeks of treatment, while 96 percent of those treated for 12 weeks eliminated the liver virus, as verified by blood tests 24 weeks after completion of treatment.
Longer term relapses were not considered. (If the virus is undetectable 24 weeks after completing treatment – known as sustained virologic response, or SVR 24 – a patient is considered cured. Later ‘relapses’ don’t count.)
Side effects, but not real serious, were seen in more than 10 percent of patients. They included headache, fatigue, nausea, insomnia and diarrhea.
“We are pleased that the data remain consistent and robust,” lead researcher Dr. Kris Kowdley in said an interview. “The data confirm that the 12-week treatment appears to be optimal.” For larger late-stage trials, the company plans to test the drug combination for 12 weeks, in order“to help the greatest number of patients achieve virologic cure.”
AbbVie said it is testing regimens with fewer drugs and ones that do not include the older oral drug ribavirin, which can also be difficult for some patients to tolerate. However, patients in the AbbVie Aviator study had the most common, but hardest to treat, genotype 1 variation of the infectious virus.
The AbbVie regimen included three experimental direct acting antiviral drugs that each attack a different target necessary for virus replication. The drugs were the protease inhibitor ABT-450, whose effect was boosted by a widely used antiviral called ritonavir; the polymerase inhibitor ABT-333, and ABT-267 from a class known as NS5A inhibitors. Those were given along with the older medicine ribavirin.
Kowdley, director of the Liver Center of Excellence at Virginia Mason Medical Center in Seattle, said the trial also showed impressive results among patients who had failed to benefit from earlier therapy.
AbbVie said the safety of the tested drugs was similar to that seen in results presented last year. Of the 247 patients evaluated, serious side effects were seen in four patients (1.6 percent), while seven patients had elevated levels of liver enzymes that can be considered a potential sign of toxicity.
Bristol-Myers Squibb
A hepatitis C drug combination from Gilead Sciences Inc. (GILD) and Bristol-Myers Squibb Co. (BMY) cured all patients in a trial, demonstrating the success of a cocktail that may never be approved for lack of co-operation (profits)!
The lack of a late-stage study, and the expense of the pills, will probably put the Gilead-Bristol combination out of reach for doctors and patients, said Geoffrey Dusheiko, a professor of medicine at the Royal Free Hospital in London.
“It’s a conundrum for us,” Dusheiko said in an interview after the results were presented at the European Association For the Study of the Liver’s conference. “It looks a very promising regimen, it really does. But I’m really not sure it’ll see the light of day.”
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This past November 2012, Bristol-Myers Squibb (BMS) announced the final results from trials conducted with Gilead Sciences for the treatment of hepatitis C (HCV). The two companies each own a drug that, in combination, has cured hepatitis C patients within 12 weeks. The results of the all-oral combination (without ribavirin or interferon) are a huge advance, not only due to the remarkable results, but because the only reported side effects were headache, fatigue, and nausea.
The cure rate for HCV was very good – without the use of toxic ribavirin or interferon. In these trials, Bristol Myers-Squibb, using its drug daclatasvir in combination with sofosbuvir from Gilead Sciences, achieved a major milestone: a high cure rate for the most prevalent types of Hepatitis C.
Nelson and colleagues conducted two randomized phase 3 trials, the final testing studies before a drug can be considered for approval. The studies, sponsored by Gilead, the maker of the drug sofosbuvir, were conducted with patients who had one of two types of chronic hepatitis C infection. In a trial called POSITRON, a group of 278 patients who could not take interferon took a combination of oral sofosbuvir and ribavirin or a placebo for 12 weeks. In a trial called FUSION, a group of 201 patients who had no response to prior interferon therapy took the drugs for 12 weeks or 16 weeks.
Sofosbuvir and ribivarin attack the virus itself, preventing the virus from replicating. Because the hepatitis C virus only lives and reproduces in the liver, the combination of antiviral compounds enables the body to eventually clear itself of the virus.
Viral reproduction was successfully suppressed during treatment for patients in both trials. The trials resulted in complete elimination of the virus in 78 percent of patients for whom interferon was not an option and for 50 percent to 73 percent of patients with prior treatment failure.
Bristol-Myers, based in New York, was working on the combination with Pharmasset Inc., which developed sofosbuvir, when Gilead bought the company for $10.8 billion in 2011. Gilead subsequently focused on developing sofosbuvir in combination with its own drug, ledipasvir. That combination cured 100 percent of patients in a mid-stage patient study, and the company is testing it in two late-stage studies.
Gilead and Bristol have planned no further trials of the combo because Foster City, California-based Gilead is focusing on a cocktail that contains only its own drugs.
Bristol is “committed to driving advances in hepatitis C research both through internal development and external collaborations to study the best treatments” and is working with Johnson & Johnson (JNJ)’s Janssen unit to study daclatasvir with simeprevir, it said in an e-mail.
Still, while ledipasvir may be effective against patients with hepatitis C genotype 1, the most common form worldwide, it may not work for those with genotype 3, which accounts for about 25 percent of cases in Europe and 45 percent in the U.K., said Graham Cooke, a clinician at Imperial College London. Daclatasvir and sofosbuvir are both active in that group, he said.
“We probably have a better option for G3 that we could be using if the companies were cooperating,” Cooke said in an interview. “Daclatasvir and sofosbuvir looks much better but Gilead very clearly wanted to develop in-house.”
Bristol-Myers Squibb unveiled data from a smaller mid-stage study of its three-drug combination that does not include ribavirin. Its program is behind those of Gilead and AbbVie, but cure rates in excess of 90 percent and a relatively clean safety profile are expected to make it a formidable player in the field.
Gilead Sciences Inc.
Gilead and Bristol have planned no further trials of the combo because Foster City, California-based Gilead is focusing on a cocktail that contains only its own drugs. “We believe that we have been able to advance the development of SOF (sofosbuvir)/ledipasvir much more quickly than would have been possible with any inter-company collaboration,” Gilead’s chief scientific officer Norbert Bischofberger said in an e-mail.
Analysts see the Gilead drug winning regulatory approval as early as 2014, with AbbVie close behind. Gilead has been given an edge by many analysts because its experimental regimen involves fewer drugs and may be closer to reaching the market. “AbbVie looked good, but I think Gilead is still in the lead,” said Tim Nelson, an analyst with Nuveen Asset Management.
In a study among 41 patients of Gilead’s sofosbuvir with Bristol’s daclatasvir, with or without the generic antiviral ribavirin, 40 were virus-free 12 weeks after six months of treatment, according to results presented yesterday in Amsterdam. The other patient didn’t turn up to the last appointment and was later found to be virus-clear. All the patients had failed prior treatment with either Vertex Pharmaceuticals Inc. (VRTX)’s Incivek or Merck & Co. (MRK)’s Victrelis.
Off-Label Combo?
Still, doctors may be tempted to prescribe the Gilead-Bristol combo “off-label” once both drugs are approved, said Mark Thursz, secretary-general of the European liver association.
“Lots of investigators around Europe and the U.S. are itching for the opportunity to put together what they believe to be the optimum combination for our patients,” Thursz said. “The only barrier to that is what is the combination cost going to be because I suspect there will be package deals to be had.”
The combination had previously demonstrated success in patients who hadn’t been treated before. Those who have failed Incivek or Victrelis are “perhaps the most difficult-to-treat population” and have no current options, said Mark Sulkowski, a doctor at Johns Hopkins University in Baltimore who presented the results.
Prescribing the two drugs as an off-label combination may be too expensive because they’ll probably have high prices as individual therapies whereas Gilead’s cocktail may be cheaper, he said.
Off-label use may also be dangerous, said Jean-Michel Pawlotsky, a professor of medicine at the University of Paris-Est. “We don’t have enough safety data,” Pawlotsky said in an interview.“If a doctor does that and there’s a major accident, the doctor is liable. It’s dangerous but I know that people will do it.”