FOSTER CITY, Calif.–(BUSINESS WIRE)–Gilead Sciences, Inc. (Nasdaq:GILD) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for an investigational, once-daily fixed-dose combination of the nucleotide analog polymerase inhibitor sofosbuvir (SOF), approved as Sovaldi® in December 2013, and velpatasvir (VEL), an investigational pan-genotypic NS5A inhibitor, for the treatment of chronic genotype 1-6 hepatitis C virus (HCV) infection. The NDA is supported by clinical studies exploring the use of 12 weeks of SOF/VEL for patients with genotype 1-6 HCV infection, including patients with compensated cirrhosis and 12 weeks of SOF/VEL with ribavirin for patients with decompensated cirrhosis.
“As the first fixed-dose combination of two pan-genotypic, direct-acting antivirals, SOF/VEL represents an important step forward in the treatment of patients with hepatitis C,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. “Genotype 1 is the most prevalent form of HCV in the United States, but worldwide, more than half of people living with HCV are infected with other genotypes. SOF/VEL complements our current HCV portfolio of Sovaldi and Harvoni, offering high cure rates and the potential to simplify treatment and eliminate the need for HCV genotype testing.”
The FDA has assigned SOF/VEL a Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options. The NDA for SOF/VEL is supported by data from four Phase 3 ASTRAL trials, which evaluated the fixed-dose combination in hepatitis C genotypes 1-6. Of the 1,035 patients treated with SOF/VEL for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 (98 percent) achieved the primary efficacy endpoint of SVR12. The ASTRAL-4 study randomized 267 patients with decompensated cirrhosis (Child-Pugh class B) to receive 12 weeks of SOF/VEL with or without ribavirin (RBV), or 24 weeks of SOF/VEL. Those who received SOF/VEL plus RBV for 12 weeks achieved an SVR12 rate of 94 percent,while those who received SOF/VEL for 12 weeks and 24 weeks achieved SVR12 rates of 83 percent and 86 percent, respectively.
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Showing posts with label FDA breakthrough designation. Show all posts
Showing posts with label FDA breakthrough designation. Show all posts
Thursday, October 29, 2015
Tuesday, June 2, 2015
FDA addresses concerns on approval of drugs to treat chronic hepatitis C
Public Release:1-Jun-2015
Wiley
Wiley
Treatment options for chronic hepatitis C, a serious and life-threatening infection, have improved substantially and several new regimens with shorter durations and improved efficacy and safety profiles are now available.
Groups have raised concerns about the evidence used to support the approval of some newer drugs, however, and the issue has been used to cast doubt on their efficacy and even to question treatment or deny reimbursement.
To address these concerns, the US Food and Drug Administration's Division of Antiviral Products in the Center for Drug Evaluation and Research (CDER) has published a paper that highlights the agency's scientific approaches and regulatory processes that support the development and approval of promising drugs to treat hepatitis C.
"FDA's approach to evaluation of recent hepatitis C drugs underscores the Agency's flexibility in considering innovative or alternative trial designs for drugs that have demonstrated highly promising outcomes in early phase development," said Dr. Poonam Mishra, deputy director for Safety, Division of Antiviral Products/Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research and lead author of the Hepatology paper. "Expedited approaches can be used without compromising efficacy standards for drugs that demonstrate breakthrough therapy potential."
Groups have raised concerns about the evidence used to support the approval of some newer drugs, however, and the issue has been used to cast doubt on their efficacy and even to question treatment or deny reimbursement.
To address these concerns, the US Food and Drug Administration's Division of Antiviral Products in the Center for Drug Evaluation and Research (CDER) has published a paper that highlights the agency's scientific approaches and regulatory processes that support the development and approval of promising drugs to treat hepatitis C.
"FDA's approach to evaluation of recent hepatitis C drugs underscores the Agency's flexibility in considering innovative or alternative trial designs for drugs that have demonstrated highly promising outcomes in early phase development," said Dr. Poonam Mishra, deputy director for Safety, Division of Antiviral Products/Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research and lead author of the Hepatology paper. "Expedited approaches can be used without compromising efficacy standards for drugs that demonstrate breakthrough therapy potential."
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Tuesday, May 26, 2015
FDA Grants Breakthrough Therapy Designation for Genotype 1 Hepatitis C Therapy
The daclatasvir-sofosbuvir regimen for the treatment of genotype 1 hepatitis C patients was granted amended Breakthrough Therapy Designation by U.S. Food and Drug Administration (FDA). In the beginning of 2015, the FDA had planned to remove Breakthrough-Therapy Designation for the daclatasvir-sofosbuvir treatment since other therapies were available and had higher success for other genotypes. However, the FDA revised its first decision and decided to continue the development of this therapy for the genotype 1 hepatitis C patients addressed in ALLY-1 Trial due to its promising results.
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Monday, March 2, 2015
HCV Drugs —Alan Franciscus, Editor-in-Chief
In this month’s column, there is more good news about drugs in development. Achillion is developing a potential treatment for genotype 1 that could shorten treatment time to 6 weeks. However, there is also some disappointing news from the Food and Drug Administration (FDA)—they are rescinding the “breakthrough therapy designation” for hepatitis C drugs. Other news which is also disappointing is that the ‘one-shot’ cure for hepatitis C does not look as if it is going to pan out. Finally, data released from a small trial with sofosbuvir, pegylated interferon and ribavirin to treat genotype 2 and 3 shows that it may help cure some people with genotype 3 and advanced liver disease.
Achillion
Achillion has had HCV drugs in development for almost as long as the HCV Advocate has been reporting on HCV inhibitors. Their latest drug and clinical trial—ACH-3102—combined with sofosbuvir (brand name Sovaldi)—was given to 12 HCV genotype 1 treatment-naïve patients for 6 weeks. One hundred percent (12 of 12 patients) achieved SVR 12 (virologic cure). Achillion is exploring additional trials with their other HCV inhibitors and perhaps shorter treatment durations (4 and 6 weeks). Don’t pin all your hopes on this though—there were only 12 patients in the trial. The combination should be studied in more people and the theory of treating for 4 or 6 weeks needs to be tested. However, it is worth keeping an eye on.
Achillion has had HCV drugs in development for almost as long as the HCV Advocate has been reporting on HCV inhibitors. Their latest drug and clinical trial—ACH-3102—combined with sofosbuvir (brand name Sovaldi)—was given to 12 HCV genotype 1 treatment-naïve patients for 6 weeks. One hundred percent (12 of 12 patients) achieved SVR 12 (virologic cure). Achillion is exploring additional trials with their other HCV inhibitors and perhaps shorter treatment durations (4 and 6 weeks). Don’t pin all your hopes on this though—there were only 12 patients in the trial. The combination should be studied in more people and the theory of treating for 4 or 6 weeks needs to be tested. However, it is worth keeping an eye on.
FDA
The FDA is rescinding its “breakthrough therapy designation status” from Bristol-Myers Squibb for Daclatasvir and Merck for its combination of elbasvir (MK-8742) and grazoprevir (MK-5712). “Breakthrough therapy designation status” is given to drug(s) that demonstrate a substantial improvement over existing therapies. Now that we have drugs that can cure over 90% of people with genotype 1 the newer drugs are unlikely to improve the cure rates. The standard time it takes the FDA to review an application for approval is about 10 months. Based on this it is unlikely that any new HCV drugs will be approved until 2016—at least for genotypes 1, 2 and 4. This is unfortunate because it limits treatment choices for patients, and it affects the price of drugs already on the market. What about genotype 3? There is clearly a need for better therapies with shorter treatment durations.
The FDA is rescinding its “breakthrough therapy designation status” from Bristol-Myers Squibb for Daclatasvir and Merck for its combination of elbasvir (MK-8742) and grazoprevir (MK-5712). “Breakthrough therapy designation status” is given to drug(s) that demonstrate a substantial improvement over existing therapies. Now that we have drugs that can cure over 90% of people with genotype 1 the newer drugs are unlikely to improve the cure rates. The standard time it takes the FDA to review an application for approval is about 10 months. Based on this it is unlikely that any new HCV drugs will be approved until 2016—at least for genotypes 1, 2 and 4. This is unfortunate because it limits treatment choices for patients, and it affects the price of drugs already on the market. What about genotype 3? There is clearly a need for better therapies with shorter treatment durations.
Regulus
We have been following an on-going study of RG-101 as a possible treatment for genotype 1 that would require only one shot—yes you read that right – a possible one-shot treatment. In a small study (2 mg/kg) dose, it was reported that 6 of 14 patients were undetectable 57 days after receiving the shot. However, unfortunately, after 12 weeks that number dropped to only 4 patients. Regulus started another study at a higher dose of RG-101 (4 mg/kg), but even at the higher dose the interim results (9 of 14 patients undetectable 57 days post-shot) cure rates were not as high as the current standard of care.
We have been following an on-going study of RG-101 as a possible treatment for genotype 1 that would require only one shot—yes you read that right – a possible one-shot treatment. In a small study (2 mg/kg) dose, it was reported that 6 of 14 patients were undetectable 57 days after receiving the shot. However, unfortunately, after 12 weeks that number dropped to only 4 patients. Regulus started another study at a higher dose of RG-101 (4 mg/kg), but even at the higher dose the interim results (9 of 14 patients undetectable 57 days post-shot) cure rates were not as high as the current standard of care.
There is also the possibility that the single shot can be given in combination with 4 weeks of antiviral pills. No side effect profile was given—an important issue since the current therapy has a low side effect profile.
Sofosbuvir/PEG/RBV
Current standard of care (SOC) treatment for genotypes 2 and 3 is the combination of sofosbuvir plus ribavirin. The cure rates in the Phase 3 clinical trials of treatment-experienced patients with cirrhosis included:
Current standard of care (SOC) treatment for genotypes 2 and 3 is the combination of sofosbuvir plus ribavirin. The cure rates in the Phase 3 clinical trials of treatment-experienced patients with cirrhosis included:
- Genotype 2 = 88% (12 weeks)
- Genotype 3 = 60% (24 weeks)
While the genotype 2 cure rates are impressive the genotype 3 rates were less than optimal and a 24-week course of treatment is a considerable period of time and expense. Additional therapies are needed, but in this case perhaps interferon may be an option.
The current phase 2 study included 47 treatment-experienced patients—23 genotype 2 patients (14 with cirrhosis); 24 genotype 3 patients (12 with cirrhosis). Treatment duration was 12 weeks. The treatment was sofosbuvir, pegylated interferon (PEG) and ribavirin.
Genotype 2: Cure rates = 93% (without cirrhosis); 96% (with cirrhosis).
The cure rates for genotype 2 were similar to the cure rates seen with sofosbuvir plus ribavirin—needless to say there is no need (or desire) to include PEG.
Genotype 3: Cure rates = 83% with and without cirrhosis.
Clearly, much higher cure rates than 24 weeks of sofosbuvir plus ribavirin (without PEG).There were 4 patients who had 5 serious side effects mostly related to interferon and ribavirin.
Adding pegylated interferon, however, may be an alternate therapy for genotype 3. This regime is listed in the Guidance documents of the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) for those who can tolerate 12 weeks of PEG therapy.
There are many therapies in development to treat genotype 3 (BMS, Gilead, Merck). I hope that the FDA will recognize the need for newer therapies for genotype 3 that produce higher cure rates—especially for treatment-experienced patients with cirrhosis—that have fewer side effects and grant them “breakthrough therapy” designation. That part of the articles about Merck and BMS losing their “breakthrough designation” status was not that clear.
http://hcvadvocate.org/news/newsLetter/2015/advocate0315.html#1
Wednesday, February 11, 2015
FDA rescinds breakthrough therapy designation for daclatasvir
The FDA has rescinded breakthrough therapy designation status from Bristol-Myers Squibb for daclatasvir for the treatment of hepatitis C virus infection, according to a statement from the manufacturer.
“The FDA has informed Bristol-Myers Squibb that, due to the evolving HCV treatment landscape, the agency intends to rescind the breakthrough therapy designation for certain genotype 1 hepatitis C regimens related to daclatasvir,” the statement from Bristol-Myers Squibb said. “This will not impact our current submission/resubmission timetable of the new drug application for daclatasvir in combination with other antiviral agents for the treatment of hepatitis C.”
Daclatasvir (Bristol-Myers Squibb) was granted breakthrough therapy designation in early 2014 as part of a dual investigational regimen with asunaprevir (Bristol-Myers Squibb) for chronic HCV. BMS withdrew its application for asunaprevir from the FDA in October 2014.
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