November 11, 2013

HCV Update: Simeprevir and Sofosbuvir

...Researchers found that a new pill that combines two drugs, sofosbuvir and ledipasvir, which would be taken over a much shorter time frame (12 weeks), was successful in essentially eliminating the strain of hepatitis C that is currently untreatable. "Our data lend support to the possibility of effectively treating all patients with genotype-1 HCV with a brief, all-oral, once-daily regimen that has no known safety issues," the study says. == Unlike previous HCV treatments, which sought to enhance the immune system with interferon and other drugs, the latest group of oral medications interferes with the virus’s ability to replicate and make proteins. A US Food and Drug Administration (FDA) board recommended two such drugs—simeprevir, made by Johnson & Johnson in New Brunswick, New Jersey, and sofosbuvir from Gilead Sciences in Foster City, California—for approval last week. When each is taken in combination with a drug called ribavirin, the treatment eliminates hepatitis C in around 80 percent of people. “This is the first time in the history of humankind that we have a cure for a viral disease,” says pharmacologist Raymond Schinazi of Emory University in Atlanta, Georgia. === Among the new drugs, the one garnering the most excitement is sofosbuvir, from Gilead Sciences, which is expected to be approved by the Food and Drug Administration by Dec. 8. It inhibits the virus’s polymerase enzyme, which builds new genomes out of RNA so the virus can replicate. Sofosbuvir is an evil decoy of sorts. It looks like a building block of RNA. But once it is mistakenly incorporated into the RNA chain, the chain cannot grow and the virus cannot reproduce. The effectiveness of the new drugs can vary depending on which strain of hepatitis C, known as genotypes, the patient has. People infected with hepatitis C genotypes 2 and 3 — which account for 20 to 25 percent of cases in the United States — will take sofosbuvir with ribavirin but without interferon, making this the first all-oral treatment for hepatitis C. Treatment for genotype 2 will be 12 weeks, but for genotype 3 it will probably be 24 weeks. Genotype 1, which accounts for more than 70 percent of patients in the United States, will still require interferon and ribavirin along with sofosbuvir, but only for 12 weeks. In a clinical trial, about 90 percent of previously untreated patients taking this combination achieved a sustained virologic response. The combination is expected to be somewhat less effective in those for whom previous treatments did not work.

November 01, 2009

Twice Daily Dosing Of Vertex Hep C Drug Works Well

Vertex Pharmaceuticals Inc's closely watched hepatitis C drug telaprevir proved nearly equally effective in a twice daily regimen as three times a day, knocking out the virus in more than 80 percent of patients in both groups in a small study.

All previous Phase II studies of the highly promising experimental drug tested the medicine at three times a day dosing given at eight-hour intervals. This study hoped to show telaprevir could be administered twice a day 12 hours apart, which would be more convenient for patients.

Patients who received telaprevir twice a day in combination with the standard treatments of pegylated-interferon and ribavirin had a sustained viral response (SVR) of 82 percent in one arm and 83 percent in another, depending on which brand of interferon they received.

That compared with 81 percent and 85 percent of patients who were given telaprevir in the three times daily regimen, according to data to be presented at the American Association for the Study of Liver Diseases (AASLD) meeting in Boston.

The percentage of patients in whom the virus is undetectable 24 weeks after completing treatment yields the critical measure known as sustained viral response, or SVR, which is considered tantamount to a cure.

"SVR rates of 75 to 80 percent (in twice daily dosing) would be very well received by investors," Sanford Bernstein analyst Geoffrey Porges said prior to release of the data.

"I was expecting around 70 percent," Dr Patrick Marcellin, the study's lead investigator, said in an interview.

"This is the highest we have observed with this triple therapy and the major conclusion is that the rate of SVR is similar in those patients who received bid (twice daily) and those who received it three times daily," said Marcellin, a professor of medicine at the University of Paris and head of Viral Hepatitis Research Center in Hospital Beaujon.

Importantly, Marcellin noted, even though the telaprevir dose was higher in the twice daily regimen, there were "no new side effects, and that is very encouraging."

Investors may also be encouraged by the low 3 percent dropout rate due to serious rash, which had been a source of some concern in earlier studies. Just four of 161 patients discontinued treatment due to rash, with another three pulling out due to anemia.

Marcellin said doctors have learned how to manage the rash and are now less likely to discontinue treatment as a result.

The open label study tested treatment naive patients, or those who had not received prior treatment for the serious liver disease. Treatment duration depended on how quickly patients responded to the medicines, an approach known as response-guided therapy.

Patients who achieved rapid viral response, defined as undetectable levels of virus at week four, and who maintained undetectable levels through week 20, were able to stop all treatment after 24 weeks of therapy -- 12 weeks on the three- drug combination and 12 more of standard therapy.

They were then followed for six months post treatment to determine whether they achieved SVR.

Eighteen percent of patients in the study did not meet that rapid response criteria and received a total of 48 weeks of treatment with the standard drugs.

Three percent of patients in the study relapsed during post-treatment follow-up, the company said.

"This study confirms that 24 weeks can be used in the large majority of patients with with high efficacy. Shorter duration means less side effects and better quality of life," Marcellin said, noting that "tailoring treatments according to the very early response improves the management of the patient and the chance of the patient to be cured."

There has been high hope that telaprevir will allow for 24 weeks of treatment for many patients. The current drugs must be taken for 48 weeks and are often difficult to tolerate, with many patients suffering flu-like symptoms for the duration.

"Many of these patients are relatively young and very active, so to treat shorter is a real benefit," Marcellin said.

He cautioned that this was a small study and that much larger Phase III clinical trials must confirm the results.

But he added: "As a clinician for our patients, this is an important hope for the future. This is a big step in the history of the treatment hepatitis C."

Vertex Hep C Drug Cures 80% at New Dose: Study

More than 80% of hepatitis C patients were cured after treatment with a new twice-daily dose of the experimental drug telaprevir made by Vertex Pharmaceuticals, according to data from a phase II study.

Data from the new study demonstrates that a more convenient twice-daily dose of telaprevir is just as effective and safe as the thrice-daily dose, Vertex said.

The hepatitis C cure rates of greater than 80% across all four patient groups of the study are also the highest ever recorded in any telaprevir study to date and exceed the cure rates reported in separate studies of boceprevir, a competing hepatitis C drug under development by Schering-Plough(SGP Quote).

Generally speaking, investors were looking for telaprevir cure rates of greater than 70%, with a difference between the twice-daily and three-times-daily dosing group of 10% or less. The data from the telaprevir study exceeded those expectations on both measures.

"These data greatly enhance the potential for twice-daily telaprevir dosing," said Vertex chief medical officer Bob Kauffman.

Vertex and partner Johnson & Johnson will formally present data from this new telaprevir study -- dubbed "C208" -- Tuesday at the annual meeting of the American Association for the Study of Liver Disease, a large gathering of hepatitis C researchers.

Investors are keenly interested in the outcome of the C208 study because it has the potential to strengthen telaprevir against competing hepatitis C drugs that while still in earlier stages of testing are being dosed once or twice a day.

Vertex Hep C Drug Improves Cure Rates

Vertex Pharmaceuticals released additional clinical data Wednesday demonstrating the potential for its experimental hepatitis C drug telaprevir to significantly improve the cure rates in patients who failed prior treatment.

nterim data from an ongoing phase II study showed that treatment with a telaprevir-based regimen resulted in rates of sustained viral responses (SVR), or hepatitis C cures, ranging from 55% to 90% across four different patient groups, all of whom failed to respond to prior therapy to varying degrees.

To put these results in perspective, last March, Vertex presented data from a different phase II study that treated patients who also failed prior therapies. In that study, 55% of patients re-treated with a telaprevir-containing regimen achieved an SVR, or cure, compared with 14% of patients who were re-treated with current standard of care.

The new data released Wednesday, therefore, appear to bolster Vertex's claim that telaprevir can improve the cure rate for even the most difficult-to-treat patients -- those who don't respond to standard hepatitis C therapy of long-acting interferon and ribavirin.

That claim needs to be proven, of course, which is why Vertex is running telaprevir through an extensive phase III trial program. Results from studies in both treatment-naive and treatment-failure hepatitis C patients are expected in the middle of next year.

Vertex has competition in the race to develop the first new drug that acts directly against the virus causing hepatitis C. Schering-Plough also has a drug, boceprevir, in phase III studies which has shown promising results in earlier studies. However, boceprevir doesn't appear to work as well as telaprevir in treatment-resistant patients