Olysio (simeprevir) label revised‏

Information about FDA Hepatitis product approvals, safety warnings, medical product labeling changes, notices of upcoming public meetings, and notices about proposed regulatory guidances.

 On October 5, 2015 FDA approved revisions to the Olysio (simeprevir) label to include dosing recommendations for the treatment of HCV/HIV-1 coinfection and to expand the indications and usage to include genotype 4 infection.

The recommended dosage regimens and treatment duration for genotype 1 and HCV/HIV-1 co-infected patients was added to the following table:

Table 1: Recommended Dosage Regimens and Treatment Duration for OLYSIO, Peg IFN alfa, and RBV Combination Therapy for Treatment of CHC Infection in HCV Genotype 1 or 4 Mono infected and HCV/HIV 1  Co infected Patients
Patient Population	Treatment Regimen and Duration
Treatment naïve patients and prior relapsers*
with or without cirrhosis, who are not co infected with HIV	12 weeks of OLYSIO in combination with Peg IFN alfa and RBV followed by an additional 12 weeks of Peg IFN alfa and RBV (total treatment duration of 24 weeks)†
without cirrhosis, who are co infected with HIV
with cirrhosis, who are co infected with HIV	12 weeks of OLYSIO in combination with Peg-IFN-alfa and RBV followed by an additional 36 weeks of Peg IFN alfa and RBV (total treatment duration of 48 weeks)†
Prior non responders (including partial‡ and null responders#), with or without cirrhosis, with or without HIV co infection	12 weeks of OLYSIO in combination with Peg-IFN-alfa and RBV followed by an additional 36 weeks of Peg IFN alfa and RBV (total treatment duration of 48 weeks)†

†HIV = human immunodeficiency virus.
* Prior relapser: HCV RNA not detected at the end of prior IFN based therapy and HCV RNA detected during follow up [see Clinical Studies (14)].
‡† Recommended duration of treatment if patient does not meet stopping rules (see Table 3).
#‡ Prior partial responder: prior on-treatment ≥ 2 log10 IU/mL reduction in HCV RNA from baseline at Week 12 and HCV RNA detected at end of prior IFN based therapy [see Clinical Studies (14)].
§# Prior null responder: prior on treatment < 2 log10 reduction in HCV RNA from baseline at Week 12 during prior IFN based therapy [see Clinical Studies (14)].

Section 6 Adverse Reactions was updated with the following information.

OLYSIO in combination with Peg IFN alfa and RBV was studied in 106 subjects with HCV genotype 1/HIV 1 co infection. The safety profile in HCV/HIV co-infected subjects was generally comparable to HCV mono infected subjects.

OLYSIO in combination with Peg IFN alfa and RBV was studied in 107 subjects with HCV genotype 4 infection. The safety profile of OLYSIO in subjects with HCV genotype 4 infection was comparable to subjects with HCV genotype 1 infection.

Azithromycin, bedaquiline and dolutegravir were added to the list of drugs without clinically significant interactions with OLYSIO (see section 7.4 of the label).

Section 12.3 Pharmacokinetics was updated to include the following statements.

Patients co infected with HIV 1

Simeprevir exposures were slightly lower in subjects with HCV genotype 1 infection with HIV 1 co infection compared to subjects with HCV genotype 1 mono infection. This difference is not considered to be clinically meaningful.

Section 12.4 Microbiology was updated to include data on genotype 4 as follows:

Chimeric replicons carrying NS3 sequences derived from HCV protease inhibitor treatment naïve genotype 4a-, 4d-, or 4r infected patients displayed median FC in EC50 values of 0.5 (IQR: 0.4 to 0.6; N=38), 0.4 (IQR: 0.2 to 0.5; N=24), and 1.6 (IQR: 0.7 to 4.5; N=8), compared to reference genotype 1b replicon, respectively. A pooled analysis of chimeric replicons carrying the NS3 sequences from HCV protease inhibitor naïve patients infected with other HCV genotype 4 subtypes, including 4c (N=1), 4e (N=2), 4f (N=3), 4h (N=3), 4k (N=1), 4o (N=2), 4q (N=2), or unidentified subtype (N=7) displayed a median FC in EC50 value of 0.7 (IQR: 0.5 to 1.1; N=21) compared to reference genotype 1b replicon.

In the RESTORE trial in genotype 4 infected subjects, 30 out of 34 (88%) subjects who did not achieve SVR had emerging amino acid substitutions at NS3 positions Q80, T122, R155, A156 and/or D168 (mainly substitutions at position D168; 26 out of 34 [76%] subjects), similar to the emerging amino acid substitutions observed in genotype 1 infected subjects.

Table 11: SVR12 Rates by IL28B rs12979860 Genotype in Adult Patients Receiving OLYSIO 150 mg Once Daily in Combination with Peg IFN alfa and RBV (Trials C212 and RESTORE)
Trial (Population)	IL28B  rs12979860  Genotype	Treatment- Naïve  Subjects % (n/N)	Prior  Relapsers % (n/N)	Prior Partial Responders % (n/N)	Prior Null Responders % (n/N)
C212 (HIV 1 co infection)	C/C	100 (15/15)	100 (7/7)	100 (1/1)	80 (4/5)
	C/T	70 (19/27)	100 (6/6)	71 (5/7)	53 (10/19)
	T/T	80 (8/10)	0 (0/2)	50 (1/2)	50 (2/4)
RESTORE (HCV genotype 4)	C/C	100 (7/7)	100 (1/1)	-	-
	C/T	82 (14/17)	82 (14/17)	60 (3/5)	41 (9/22)
	T/T	0 (8/10)	00 (4/4)	60 (3/5)	39 (77/18)

SVR12: sustained virologic response 12 weeks after planned EOT.

Section 14 Clinical Studies was updated to include the trial results from the HCV/HIV- coinfected trial and the genotype 4 trial.

Subjects with HCV/HIV 1 Co Infection
C212 was an open label, single arm Phase 3 trial in HIV 1 subjects co infected with HCV genotype 1 who were treatment naïve or failed prior HCV therapy with Peg IFN alfa and RBV (including prior relapsers, partial responders or null responders). Non cirrhotic treatment naïve subjects or prior relapsers received 12 weeks of once daily treatment with 150 mg OLYSIO plus Peg IFN alfa 2a and RBV, followed by 12 or 36 weeks of therapy with Peg IFN alfa 2a and RBV in accordance with the protocol defined RGT criteria. Prior non responder subjects (partial and null response) and all cirrhotic subjects (METAVIR fibrosis score F4) received 36 weeks of Peg IFN alfa 2a and RBV after the initial 12 weeks of OLYSIO in combination with Peg IFN alfa 2a and RBV.

The 106 enrolled subjects in the C212 trial had a median age of 48 years (range: 27 to 67 years; with 2% above 65 years); 85% were male; 82% were White, 14% Black or African American, 1% Asian, and 6% Hispanic; 12% had a BMI greater than or equal to 30 kg/m2; 86% had HCV RNA levels greater than 800,000 IU/mL; 68% had METAVIR fibrosis score F0, F1 or F2, 19% METAVIR fibrosis score F3, and 13% METAVIR fibrosis score F4; 82% had HCV genotype 1a, and 17% HCV genotype 1b; 28% of the overall population and 34% of the subjects with genotype 1a had Q80K polymorphism at baseline; 27% had IL28B CC genotype, 56% IL28B CT genotype, and 17% IL28B TT genotype; 50% (n=53) were HCV treatment naïve subjects, 14% (n=15) prior relapsers, 9% (n=10) prior partial responders, and 26% (n=28) prior null responders. Eighty eight percent (n=93) of the subjects were on highly active antiretroviral therapy (HAART), with nucleoside reverse transcriptase inhibitors and the integrase inhibitor raltegravir being the most commonly used HIV antiretroviral. HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors (except rilpivirine) were prohibited from use in this study.

The median baseline HIV 1 RNA levels and CD4+ cell count in subjects not on HAART were 4.18 log10 copies/mL (range: 1.3 4.9 log10 copies/mL) and 677 × 106 cells/L (range: 489 1076 × 106 cells/L), respectively. The median baseline CD4+ cell count in subjects on HAART was 561 × 106 cells/mL (range: 275 1407 × 106 cells/mL).

Table 17 shows the response rates in treatment naïve, prior relapsers, prior partial responders and null responders.

Table 17: Response Rates in Adult Subjects with HCV Genotype 1 Infection and HIV 1 Co Infection (C212 Trial)
Response Rates	Treatment Naïve Subjects N=53 % (n/N)	Prior Relapsers N=15 % (n/N)	Prior Partial Responders N=10 % (n/N)	Prior Null Responders N=28 % (n/N)
Overall SVR12 (genotype 1a and 1b) Genotype 1a Genotype 1b	79 (42/53) 77 (33/43) 90 (9/10)	87 (13/15) 83 (10/12) 100 (3/3)	70 (7/10) 67 (6/9) 100 (1/1)	57 (16/28) 54 (13/24) 75 (3/4)
Outcome for all subjects without SVR12
On treatment failure*	9 (5/53)	0 (0/15)	20 (2/10)	39 (11/28)
Viral relapse†	10 (5/48)	13 (2/15)	0 (0/7)	12 (2/17)

150 mg OLYSIO for 12 weeks with Peg IFN alfa 2a and RBV for 24 or 48 weeks.
* On treatment failure was defined as the proportion of subjects with confirmed detectable HCV RNA at EOT (including but not limited to subjects who met the protocol specified treatment stopping rules and/or experienced viral breakthrough).
† Viral relapse rates are calculated with a denominator of subjects with undetectable HCV RNA at actual EOT and with at least one follow up HCV RNA assessment. Includes one prior null responder who experienced relapse after SVR12.

Eighty nine percent (n=54/61) of the OLYSIO treated treatment naïve subjects and prior relapsers without cirrhosis were eligible for a total treatment duration of 24 weeks. In these subjects, the SVR12 rate was 87%.

Seventy-one percent (n=37/52), 93% (n=14/15), 80% (n=8/10) and 36% (n=10/28) of OLYSIO treated treatment naïve subjects, prior relapsers, prior partial responders and prior null responders had undetectable HCV RNA at week 4 (RVR). In these subjects the SVR12 rates were 89%, 93%, 75% and 90%, respectively.

Table 18 shows the SVR rates by METAVIR fibrosis scores.

Table 18: SVR12 Rates by METAVIR Fibrosis Score in Adult Subjects with HCV Genotype 1 Infection and HIV 1 co Infection (C212 Trial)
Subgroup	Treatment Naïve  Subjects % (n/N)	Prior  Relapsers % (n/N)	Prior Partial Responders % (n/N)	Prior Null Responders % (n/N)
F0 2	89 (24/27)	78 (7/9)	50 (1/2)	57 (4/7)
F3 4	57 (4/7)	100 (2/2)	67 (2/3)	60 (6/10)

Two subjects had HIV virologic failure defined as confirmed HIV 1 RNA ≥ 200 copies/mL after previous < 50 copies/mL; these failures occurred 36 and 48 weeks after end of OLYSIO treatment.

Adult Subjects with HCV Genotype 4 Infection
RESTORE was an open label, single arm Phase 3 trial in subjects with HCV genotype 4 infection who were treatment naïve or failed prior therapy with Peg IFN alfa and RBV (including prior relapsers, partial responders or null responders). Treatment naïve subjects or prior relapsers received once daily treatment with 150 mg OLYSIO plus Peg IFN alfa 2a and RBV for 12 weeks, followed by 12 or 36 weeks of therapy with Peg IFN alfa 2a and RBV in accordance with the protocol defined RGT criteria. Prior non responder subjects (partial and null response) received once daily treatment with 150 mg OLYSIO plus Peg IFN alfa 2a and RBV for 12 weeks, followed by 36 weeks of Peg IFN alfa 2a and RBV.

The 107 enrolled subjects in the RESTORE trial with HCV genotype 4 had a median age of 49 years (range: 27 to 69 years; with 5% above 65 years); 79% were male; 72% were White, 28% Black or African American, and 7% Hispanic; 14% had a BMI greater than or equal to 30 kg/m2; 60% had HCV RNA levels greater than 800,000 IU/mL; 57% had METAVIR fibrosis score F0, F1 or F2, 14% METAVIR fibrosis score F3, and 29% METAVIR fibrosis score F4; 42% had HCV genotype 4a, and 24% had HCV genotype 4d; 8% had IL28B CC genotype, 58% IL28B CT genotype, and 35% IL28B TT genotype; 33% (n=35) were treatment naïve HCV subjects, 21% (n=22) prior relapsers, 9% (n=10) prior partial responders, and 37% (n=40) prior null responders.

Table 19 shows the response rates in treatment naïve, prior relapsers, prior partial responders and null responders. Table 20 shows the SVR rates by METAVIR fibrosis scores.

Table 19: Response Rates in Adult Subjects with HCV Genotype 4 Infection (RESTORE Trial)
Response Rates	Treatment Naïve Subjects N=35 % (n/N)	Prior Relapsers N=22 % (n/N)	Prior Partial Responders N=10 % (n/N)	Prior Null Responders N=40 % (n/N)
Overall SVR12	83 (29/35)	86 (19/22)	60 (6/10)	40 (16/40)
Outcome for all subjects without SVR12
On treatment failure*	9 (3/35)	9 (2/22)	20 (2/10)	45 (18/40)
Viral relapse†	9 (3/35)	5 (1/22)	20 (2/10)	15 (6/40)

150 mg OLYSIO for 12 weeks with Peg IFN alfa 2a and RBV for 24 or 48 weeks.
* On treatment failure was defined as the proportion of subjects with confirmed detectable HCV RNA at EOT (including but not limited to subjects who met the protocol specified treatment stopping rules and/or experienced viral breakthrough).
† Viral relapse rates are calculated with a denominator of subjects with undetectable (or unconfirmed detectable) HCV RNA at actual EOT.

Table 20: SVR12 Rates by METAVIR Fibrosis Score in Adult Subjects with HCV Genotype 4 Infection (RESTORE Trial)
Subgroup	Treatment Naïve Subjects % (n/N)	Prior Relapsers % (n/N)	Prior Partial Responders % (n/N)	Prior Null Responders % (n/N)
F0-2	85 (22/26)	91 (10/11)	100 (5/5)	47 (8/17)
F3-4	78 (7/9)	82 (9/11)	20 (1/5)	35 (7/20)

You will be able to view the complete label at drugs@fda or dailymed.

Richard Klein
Office of Health and Constituent Affairs
Food and Drug Administration

Kimberly Struble
Division of Antiviral Products
Food and Drug Administration

Steve Morin
Office of Health and Constituent Affairs
Food and Drug Administration

For more information about the Hepatitis Liaison Program visit the FDA Patient Network

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U.S. FDA Grants Priority Review For Daklinza (daclatasvir) sNDA

Three applications are under review for Daklinzain combination with sofosbuvir with or without ribavirin to treat chronic hepatitis C patients with decompensated cirrhosis, post-liver transplant recurrence of HCV, and coinfection with HIV-1

Bristol-Myers Squibb’s U.S. registration focus for Daklinza is based on addressing the treatment needs of challenging HCV patient populations

October 06, 2015 07:00 AM Eastern Daylight Time

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) announced today that the U.S. Food and Drug Administration (FDA) has accepted for filing and review three supplemental New Drug Applications (sNDAs) for Daklinza (daclatasvir), an NS5A replication complex inhibitor, for use with sofosbuvir with or without ribavirin. The applications are for the treatment of patients with chronic hepatitis C (HCV) coinfected with human immunodeficiency virus (HIV-1), patients with advanced cirrhosis (including decompensated cirrhosis), and for patients with post-liver transplant recurrence of HCV.

In the U.S., the FDA grants priority review status when an investigational medicine, if approved, would offer a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. The FDA will review the three Daklinza sNDAs within a six-month timeframe.

“Hepatitis C is not a one-size-fits-all, monolithic disease. Our focus for the Daklinza-sofosbuvir regimen centers on addressing the needs of HCV patient subpopulations who need new options even in light of the extraordinary advances that have occurred in HCV treatment,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “We look forward to working with the FDA toward the goal of eventually helping many difficult-to-treat HCV patients.”

Daklinza was initially approved in the U.S. in July 2015 and is indicated for use with sofosbuvir for the treatment of patients with chronic HCV genotype 3 infection. The new sNDAs accepted by the FDA for review include data from the ALLY-1 and ALLY-2 clinical trials. ALLY-2 evaluated the once-daily 12-week combination of Daklinza and sofosbuvir for the treatment of patients with HCV coinfected with HIV-1, a patient population that historically has been challenging to treat, in large part due to the complexities of the overlapping therapeutic regimens used to treat each infection. ALLY-1 evaluated a 12-week regimen of daclatasvir and sofosbuvir once-daily with ribavirin for the treatment of patients with HCV with either advanced cirrhosis or post-liver transplant recurrence of HCV.

In May 2015, Daklinza with sofosbuvir received FDA Breakthrough Therapy Designation for HCV genotype 1 patients with advanced cirrhosis (Child-Pugh Class B or C) and those who develop genotype 1 HCV recurrence post-liver transplant. Breakthrough Therapy Designation, according to the FDA, is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for this designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.

About Bristol-Myers Squibb in HCV

Bristol-Myers Squibb’s research efforts are focused on advancing compounds to deliver the most value to HCV patients with high unmet needs. At the core of our portfolio is Daklinza, a NS5A complex inhibitor which continues to be investigated in multiple treatment regimens and in patients with high disease burden.

In July 2014, Japan became the first country in the world to approve the use of a daclatasvir-based regimen for the treatment of chronic HCV. Since then, daclatasvir-based regimens have been approved in more than 50 countries, including the United States, across Europe, and in numerous other countries in Central and South America, the Middle East and the Asia-Pacific region.

Indication and Important Safety Information - Daklinza™ (daclatasvir)

INDICATION

Daklinza™ (daclatasvir) is indicated for use with sofosbuvir for the treatment of patients with chronic hepatitis C virus (HCV) genotype 3 infection.

Limitations of Use:

Sustained virologic response (SVR) rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving Daklinza in combination with sofosbuvir for 12 weeks.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Drugs Contraindicated with Daklinza: strong inducers of CYP3A that may lead to loss of efficacy of Daklinza include, but are not limited to:
Phenytoin, carbamazepine, rifampin, St. John’s wort (Hypericum perforatum).

WARNINGS and PRECAUTIONS

-- Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: Coadministration of Daklinza and other drugs may result in known or potentially significant drug interactions. Interactions may include the loss of therapeutic effect of Daklinza and possible development of resistance, dosage adjustments for other agents or Daklinza, possible clinically significant adverse events from greater exposure for the other agents or Daklinza.

Serious Symptomatic Bradycardia When Coadministered with Sofosbuvir and Amiodarone: Post-marketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with sofosbuvir in combination with another direct-acting antiviral, including Daklinza. A fatal cardiac arrest was reported with ledipasvir/sofosbuvir.
Coadministration of amiodarone with Daklinza in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no alternative treatment options, patients should undergo cardiac monitoring, as outlined in Section 5.2 of the prescribing information.
Bradycardia generally resolved after discontinuation of HCV treatment.
Patients also taking beta blockers or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone.

ADVERSE REACTIONS

The most common adverse reactions were (≥ 5%): headache (14%), fatigue (14%), nausea (8%), and diarrhea (5%).

DRUG INTERACTIONS

CYP3A: Daklinza is a substrate. Moderate or strong inducers may decrease plasma levels and effect of Daklinza. Strong inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir) may increase plasma levels of Daklinza.
P-gp, OATP 1B1 and 1B3, and BCRP: Daklinza is an inhibitor, and may increase exposure to substrates, potentially increasing or prolonging their adverse effect.
See Section 7 of the Full Prescribing Information for additional established and other potentially significant drug interactions and related dose modification recommendations.

Daklinza in Pregnancy: No data with Daklinza in pregnant women are available to inform a drug-associated risk. Animal studies of Daklinza at exposure above the recommended human dose have shown maternal and embryofetal toxicity. Consider the benefits and risks of Daklinza when prescribing Daklinza to a pregnant woman.

Nursing Mothers: Daklinza was excreted into the milk of lactating rats; it is not known if Daklinza is excreted into human milk. Consider the benefits and risks to the mother and infant when breastfeeding.

Please click here for the Daklinza full prescribing information.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information please visit www.bms.com or follow us on Twitter at twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that Daklinza will be approved for the additional indication mentioned above. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2014 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Contacts
Bristol-Myers Squibb Company
Media:
Robert Perry, 609-419-5378
cell: 407-492-4616
rob.perry@bms.com
or
Investors:
Ranya Dajani, 609-252-5330
ranya.dajani@bms.com
or
Bill Szablewski, 609-252-5894
william.szablewski@bms.com

Patients have mixed feelings about hepatitis drugs

By Vickie Aldous
Mail Tribune

Posted Oct. 4, 2015 at 12:01 AM

Patients who have coped for years with hepatitis C have had mixed reactions to new drugs that can cure the disease, from elation about the treatment to shock about the price.

One Southern Oregon woman who asked not to be named said she went through a six-month course of older medication, but suffered side effects such as internal bleeding that required her to be hospitalized and given blood transfusions. The grueling treatment cleared her body of the virus, but three months later, the virus reemerged.

In March 2014, she started a three-month course of Sovaldi, a new medication which produced no side effects and wiped the virus from her body. The virus has not returned.

Read more....

NYU Researchers Find Development of Serious Liver Damage in Mid- to Late-adulthood Among People Who Inject Drugs with Untreated Chronic Hepatitis C Infection

October 5, 2015
N-56 2015-16

Few people who inject drugs are engaged in needed care for chronic HCV infection; Early engagement in treatment needs to be a policy priority for these individuals

The Hepatitis C virus (HCV) infection is a chronic blood-borne viral infection that affects an estimated 160 million people, or 2-3% of the population world-wide. Alarmingly, chronic HCV infection accounts for one-quarter of the cases of cirrhosis and hepatocellular carcinoma (HCC). If HCV is left untreated, chronic liver disease will occur in 60–70% of the cases, cirrhosis in 5–20% of the cases, and 1–5% will die from decompensated cirrhosis or HCC.

In most high-income countries, such as the United States, where drug injection is the primary route of HCV transmission, the disease is concentrated among people who inject drugs (PWID). While it is estimated that 50–80% of PWID are chronically infected, fewer than 5% of PWID have received treatment.

In a new study, “Hepatitis C virus (HCV) disease progression in people who inject drugs (PWID): A systematic review and meta-analysis,” published in the International Journal of Drug Policy, a team of researchers from New York University’s Center for Drug Use and HIV Research (CDUHR) assessed existing data on the natural history of HCV among PWID. A total of twenty-one studies examined over 8500 PWID, who contributed nearly 120,000 person-years at risk, for the study of four major HCV-related outcomes included in the synthesis.

Read more....

"All Natural" Alternatives for Erectile Dysfunction: A Risky Proposition

Since everything is processed by the liver, I thought it was important to post this warning...Alan

Men, beware! Products falsely marketed as “dietary supplements” or “foods” that promise to enhance your sexual performance or increase sexual stimulation might contain hidden drug ingredients or other undisclosed ingredients — and can endanger your health.

Thus far, FDA lab tests have found that nearly 300 of these products contain undisclosed drug ingredients. These can include the same active ingredients found in prescription drugs that are FDA-approved for the treatment of erectile dysfunction (ED), such as Viagra, Cialis and Levitra. Not only do these products contain undisclosed drug ingredients, but they also sometimes may include combinations of undisclosed ingredients or excessively high doses, both potentially dangerous situations.

Even a cautious consumer can’t tell that these products are, in fact, tainted with undisclosed drug ingredients, because their labels do not list the potentially hazardous ingredients, says M. Daniel Dos Santos, Pharm.D., Ph.D., of FDA’s Division of Dietary Supplement Programs. Consumers may be misled to believe these products are safe because their labeling often suggests they are “all-natural” or “herbal” alternatives to FDA-approved prescription drugs for the treatment of ED.

Read more....

Regulus to Present Updated Data Supporting RG-101 as Novel microRNA Therapeutic for the Treatment of HCV at The Liver Meeting® 2015 (AASLD)

-Phase I Clinical Data will be Featured in Viral Hepatitis Plenary Session-

LA JOLLA, Calif., Oct. 2, 2015 /PRNewswire/ -- Regulus Therapeutics Inc. (NASDAQ:RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, announced today that two abstracts related to RG-101, a GalNAc-conjugated anti-miR targeting microRNA-122 ("miR-122") for the treatment of chronic Hepatitis C Virus (HCV) infection, were accepted for presentation at The Liver Meeting®, the 66th Annual Meeting of the American Association for the Study of Liver Disease (AASLD), to be held November 13-17, 2015 in San Francisco, CA.

Viral Hepatitis Plenary Session, November 17, 2015, 8:45am - 9:00am: A Single Dose of RG-101, a GalNAc-Conjugated Oligonucleotide Targeting miR-122, Results in Undetectable HCV RNA Levels in Chronic Hepatitis C Patients at Week 28 of Follow-up

Investigators will present extended follow-up data from the Phase I clinical study of RG-101 demonstrating that a single subcutaneous administration of either 2 mg/kg or 4 mg/kg of RG-101 as monotherapy resulted in HCV RNA levels below the limit of quantification in 6/22 patients with various HCV genotypes at week 28 of follow-up.

Poster Presentation, November 17, 2015, 8:00am - 12:00pm: Treatment with the Anti-miRNA122 Oligonucleotide RG-101 Results in a Decrease in IP-10 but Does Not Affect the Levels of Other Cytokines in Patients with Chronic Hepatitis C

Investigators will present data examining immunological changes observed in the plasma of patients who received a subcutaneous administration of RG-101 in the completed Phase I study.
Results demonstrated that HCV patients had significantly higher IP-10 levels at baseline compared to healthy controls. In HCV patients who received a subcutaneous administration of RG-101, a significant decline was observed in IP-10 serum concentrations compared to baseline, and RG-101 did not trigger a systemic immune activation

Read more....

AbbVie Demonstrates Commitment to Hepatitis C Patients with New Data on VIEKIRA PAK™ and Ongoing Clinical Development Program at The Liver Meeting® 2015

Note:  There are some interesting studies of AbbVie drugs being presented that will feature new combination of drugs that will offer shorter treatment durations and more treatment options for people with genotypes 1, 2 and 3.  

- New data to be presented on VIEKIRA PAK in genotype 1 hepatitis C patients with chronic kidney disease and on AbbVie's investigational HCV pipeline medicines, ABT-493 and ABT-530

NORTH CHICAGO, Ill., Oct. 1, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global research-based biopharmaceutical company, today announced that 34 abstracts from its chronic hepatitis C clinical development program have been accepted for presentation at The Liver Meeting®, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco from November 13-17, further demonstrating AbbVie's strong leadership and ongoing commitment to patients with chronic hepatitis C virus (HCV) infection.

Presentations will highlight new data from Phase 3b studies of AbbVie's FDA-approved VIEKIRA PAK™ (ombitasvir, paritaprevir, ritonavir tablets; dasabuvir tablets), taken with or without ribavirin (RBV), for adults with genotype 1 (GT1) chronic HCV infection, including studies of GT1 patients with chronic kidney disease and genotype 1b (GT1b) patients with compensated cirrhosis. Additionally, new clinical studies will be presented on AbbVie's HCV pipeline medicines, ABT-493 and ABT-530, focused on investigating pan-genotypic, ribavirin-free, once-daily treatment options that may allow for shorter treatment durations of as little as eight weeks.

"We are pleased to present new data from studies of the VIEKIRA PAK regimen in HCV patients, including those with chronic kidney disease and GT1b compensated cirrhosis," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "These data, as well as our findings from our investigational compounds, further demonstrate AbbVie's firm commitment to supporting the care of patients with chronic HCV infection."

Select AbbVie clinical presentations include:

RUBY-I: Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir +/- Ribavirin in Non-Cirrhotic HCV Genotype 1-infected Patients With Severe Renal Impairment or End-Stage Renal Disease; Pockros, P, et al.; Poster #1039; Sunday, November 15, 2015, 8:00 a.m. – 5:30 p.m. PT; Hepatitis C: Therapeutics (Approved Agents)RUBY-I is an ongoing open-label study evaluating 3D+/-RBV in patients with stage four or five chronic kidney disease and GT1 infection.

TURQUOISE-III: 12-Week Ribavirin-Free Regimen of Ombitasvir/Paritaprevir/r and Dasabuvir for Patients with HCV Genotype 1b and Cirrhosis; Poordad, F, et al.; Poster #1051; Sunday, November 15, 2015, 8:00 a.m. – 5:30 p.m. PT; Hepatitis C: Therapeutics (Approved Agents)Hepatitis C virus infected patients have historically been more difficult to treat when they have cirrhosis. This poster reports on the safety and efficacy of the 3D regimen without RBV in patients with HCV GT1b infection and compensated cirrhosis. VIEKIRA PAK is not recommended for patients with decompensated liver disease.

Efficacy, Change in MELD Score, and Safety by Baseline MELD Score in Patients With Compensated Cirrhosis Receiving Ombitasvir/Paritaprevir/r and Dasabuvir Plus Ribavirin in Phase 3 TURQUOISE-II Trial; Jacobson, I, et al.; Poster #1106; Sunday, November 15, 2015, 8:00 a.m. – 5:30 p.m. PT; Hepatitis C: Therapeutics (Approved Agents)Model for end-stage liver disease (MELD) scores assess liver disease severity. In this analysis, the efficacy and safety of 3D+RBV and changes in MELD score by baseline MELD score is evaluated.

Preliminary Safety and Efficacy Results in TOPAZ-II: A Phase 3b Study Evaluating Long-Term Clinical Outcomes in HCV Genotype 1-infected Patients Receiving Ombitasvir/Paritaprevir/r and Dasabuvir +/-Ribavirin; Reau, N, et al.; Poster #1065; Sunday, November 15, 2015, 8:00 a.m. – 5:30 p.m. PT; Hepatitis C: Therapeutics (Approved Agents)TOPAZ-I (ex-U.S.) and TOPAZ-II (U.S.) are evaluating the impact of SVR12 on the progression of liver disease through five years post-treatment in a broad population of HCV GT1-infected patients receiving 3D+/-RBV. This interim analysis reports on-treatment safety and efficacy of 3D+/-RBV among patients in the TOPAZ-II study.

Long-Term Efficacy of Ombitasvir/Paritaprevir/r and Dasabuvir With or Without Ribavirin in HCV GT1-Infected Patients With or Without Cirrhosis; Zeuzem, S, et al.; Poster #1086; Sunday, November 15, 2015, 8:00 a.m. – 5:30 p.m. PT; Hepatitis C: Therapeutics (Approved Agents)In this analysis, the efficacy through post-treatment week 48 of the 3D regimen in HCV GT1-infected patients with or without cirrhosis is examined.

SVR4 Results in HCV Genotype 1 Non-Cirrhotic Treatment-Naïve or Pegylated Interferon/Ribavirin Null Responders with the Combination of the NS3/4A Protease Inhibitor ABT-493 and NS5A Inhibitor ABT-530 (SURVEYOR-1); Poordad, F, et al.; Oral presentation #41; Sunday, November 15, 2015, 4:00 p.m. – 4:15 p.m. PT; Parallel Session 5, Hep C Clinical TrialsIn this Phase 2 study, treatment with ABT-493 and ABT-530 for 12 weeks is evaluated in HCV GT1-infected subjects without cirrhosis. Efficacy and safety results are reported.

SVR4 Rates with the NS3/4A Protease Inhibitor ABT-493 and NS5A Inhibitor ABT-530 in Non-Cirrhotic Treatment-Naïve and Treatment-Experienced Patients With HCV Genotype 2 Infection (SURVEYOR-2); Wyles, D, et al.; Oral presentation #250; Tuesday, November 17, 2015; 12:00 p.m. – 12:15 p.m. PT; General Session, Parallel 37: Hepatitis C: Pre-approval Clinical Studies IIThis presentation evaluates the efficacy and safety of ABT-493 and ABT-530 with or without RBV in non-cirrhotic GT2-infected treatment-naïve and pegylated interferon/RBV treatment-experienced subjects.

SVR4 Rates with the NS3/4A Protease Inhibitor ABT-493 and NS5A Inhibitor ABT-530 in Non-Cirrhotic Treatment-Naïve and Treatment-Experienced Patients With HCV Genotype 3 Infection (SURVEYOR-2); Kwo, P, et al.; Oral presentation #248; Tuesday, November 17, 2015, 11:30 a.m.– 11:45 a.m. PT; General Session, Parallel 37: Hepatitis C: Pre-approval Clinical Studies IIThis presentation evaluates the efficacy and safety of ABT-493 and ABT-530 with or without ribavirin (RBV) in non-cirrhotic GT3-infected treatment-naïve and pegylated interferon/RBV treatment-experienced subjects.

Select Health Economics and Outcomes Research (HEOR) abstracts include:

Lifetime Risks of Liver Morbidity and Mortality in Patients with Chronic Genotype 1 Hepatitis C Virus and HIV Coinfection Treated with 3D±R (Ombitasvir/ Paritaprevir/ Ritonavir, Dasabuvir ± Ribavirin) vs other Standards of Care in the U.S.; Saab, S, et al.; Poster #1087; Sunday, November 15, 2015, 8:00 a.m. – 5:30 p.m.

Hepatitis C: Therapeutics (Approved Agents).  This study evaluates the lifetime risks of liver morbidity and mortality in patients with GT1 HCV and HIV coinfection treated with 3D±R for 12 or 24 weeks compared to other standards of care in the U.S.PT

The Healthcare Cost Burden of HCV-infected Baby Boomers in the U.S.; Brookmeyer R, et al.; Poster #1068; Sunday, November 15, 2015,  8:00 a.m. – 5:30 p.m. PT; Hepatitis C: Therapeutics (Approved Agents)This study quantifies healthcare costs for 50-64 year-old "baby boomers" with HCV by diagnosis and insurance status.

The full AASLD 2015 scientific program can be found at www.aasld.org.