Sofosbuvir (GS-7977) in HIV/HCV co-infected patients...

Posted 9/17/12 on Hep Mag.com. A small interferon-free Phase Ib 7-day trial of Sofosbuvir (GS-7977) plus ribavirin in 19 HIV/HCV co-infected patients yielded some impressive initial results in a population that is definitely in need of more anti-HCV options. Sofosbuvir showed no difference in viral kinetics vs non co-infected patients, no new safety signals, no HIV viral breakthrough and no added side-effects. Hopefully the larger Phase III trial in this population will be equally impressive in its results. 

Sofosbuvir (GS-7977) Shows Promise in HIV/Hep C-Coinfected People

Gilead Sciences' experimental NS5B polymerase inhibitor sofosbuvir (GS-7977) was just as likely to rapidly reduce hepatitis C virus (HCV) levels in people coinfected with HIV, compared with those living with HCV but not HIV, in a small seven-day study presented at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco. The clinical trial, which enrolled HCV/HIV-coinfected and HCV-monoinfected patients residing in Puerto Rico—75 percent of whom had difficult-to-treat genotype 1 HCV infection—also noted that side effects were no different or more severe among those with living with both viruses. After a week of sofosbuvir treatment, used without other hep C medications, HCV viral loads dropped by an average of 4 log (99.99 percent). Additionally, nearly 60 percent of patients achieved undetectable HCV viral loads during the study, with 15 percent maintaining undetectable levels seven days after treatment was discontinued. Sofosbuvir appeared to work equally well against the different HCV genotypes in the study and did not hinder the effectiveness of the antiretroviral regimens being used to suppress HIV. A Phase III clinical trial of sofosbuvir plus ribavirin enrolling people living with HCV and HIV began in July and is currently recruiting volunteers.

The emerging role of the Infectious Disease physician in treating HCV...

An article published in POZ magazine on 4/13/12 on an opinion piece e-published ahead of print in   'Clinical Infectious Diseases' authored by Barbara McGovern, MD of Tufts University School of Medicine.  She makes a plea for Infectious Disease doctors to start treating Hepatitis C and relieve some of the burden on the thin and overworked ranks of Hepatologists.  She suggests 'establishing "centers of excellence" and instituting joint fellowships wherein HCV experts can pass their knowledge along to ID physicians; presenting conferences and workshops devoted to HCV evaluation and management; collecting data from the membership of the Infectious Diseases Society of America (IDSA) on obstacles to hepatitis C patient care; and offering real-time updates to HCV treatment guidelines.'  It's my opinion that IDs offer the perfect discipline for treating HCV and HCV/HIV co-infection as newer, all-oral, interferon-free regimens greatly expand the the pool of patients elgible (and willing) to be treated.  IDs have treated HIV for years - a disease state whose early treatment years display some uncanny parallels to the genesis of Direct Acting Antiviral therapy for Hepatitis C. The IDs know virology, they understand the implications for viral resistance, the concept of 'drug cocktails' which attack the virus at different points along it's life cycle, they know about side effect management, and most of all, their economic model is strikingly similar to that of the in-the-trenches Hepatologist.  It seems like a good fit from out here looking in. 

April 13, 2012

More Infectious Disease Docs Treat Hep C

We may soon see an end to obstacles in the care of people living with chronic hepatitis C virus (HCV)—but only if infectious disease (ID) doctors work with and learn from hepatologists, according to an opinion piece authored by Barbara McGovern, MD, of Tufts University School of Medicine and published online ahead of print by Clinical Infectious Diseases.

ID specialists have historically been reluctant to treat hepatitis C, even among their own patients living with HIV, because of the complexities of prognostic testing and combination treatment, low cure rates among people with genotype 1 HCV and the need for expert management of side effects.

HCV coinfection is more amenable to treatment now than in the past—including for those coinfected with both HIV and HCV—with the current generation of direct antiviral agents providing a 75 to 85 percent cure rate.

Further improvements—such as all-oral regimens that don't involve interferon—are expected within the next few years and will likely benefit both HCV-monoinfected and HIV/HCV-coinfected patients. This would be a great boon for all people living with HCV, for whom treatment can lead to remission of liver disease and reduced risk of liver cancer and cirrhosis.

With an estimated 170 million HCV cases worldwide—including 5 million in the United States, where hepatitis C death rates now exceed those from HIV—hepatologists, the usual go-to medical experts for hepatitis C care and management, are overwhelmed by the number of patients seeking their services. Their efforts will be stretched even thinner if the Centers for Disease Control and Prevention (CDC) implements planned screening guidelines that recommend testing everyone born between 1945 and 1965—an age range with an especially high HCV prevalence.

Bringing more people into care for hepatitis C, McGovern argues, will require expanding the ranks of ID specialists capable of dealing with the virus and its complications.

One reason HCV care has required highly specialized attention from hepatologists was the need for a liver biopsy to measure the progress of the disease. This may no longer be necessary, thanks to noninvasive testing via such methods as blood tests and elastography (measurement of tissue stiffness via ultrasound or magnetic resonance), which can be performed by ID specialists.

Another main reason why hepatologists have been needed for HCV therapy is the risk of decompensated cirrhosis—when a cirrhotic liver begins to lose its ability to function—for patients who don't receive antiviral therapy or whose therapy fails. Managing the complications of decompensated cirrhosis requires a hepatologist's specialized training. However, early HCV treatment greatly decreases the risks of cirrhosis.

Lastly, modern combo therapies for HCV require extensive knowledge of the relevant antiviral drugs and their interactions.

McGovern recommends sidestepping this dearth of hepatologists by cross-training ID specialists in the intricacies of HCV infection. Her recommendations include establishing "centers of excellence" and instituting joint fellowships wherein HCV experts can pass their knowledge along to ID physicians; presenting conferences and workshops devoted to HCV evaluation and management; collecting data from the membership of the Infectious Diseases Society of America (IDSA) on obstacles to hepatitis C patient care; and offering real-time updates to HCV treatment guidelines.

"Although HCV does not command the same media attention as for some emerging infectious diseases," McGovern wrote, "advancing liver disease will be exacting a tremendous toll in morbidity and mortality in the decades to come if wider access to treatment is not realized in the near future. In fact, in 2007, deaths from HCV infection exceeded deaths from HIV in the United States. Millions of HCV-infected patients will be depending on an expeditious response from the ID community, as we have done for many other infections in the past."

Encouraging Phase II Telaprevir HIV/HCV coinfection treatment data presented at CROI...

Posted on March 6 on Vertex Pharmaceuticals.com: Data presented at CROI from the Phase II Telaprevir trial looking at the safety and effectiveness of Telaprevir + P/R in the HIV/HCV co-infected patient (all on Atripla and Reyataz as their antiretroviral regimen).  While this is SVR12 data and not the 'true' SVR of 24 weeks past End of Treatment (EOT), this data looks encouraging with 74% (28/38) patients undetectable at SVR12.  Given the huge potential of drug-drug-interactions with Telaprevir and antiretroviral regimens, it looks as if the Atripla + Reyataz regimen in combination with TVR + P/R is the one to go with - VERY encouraging in that there have been no HIV breakthroughs while on TVR + P/R + Reyataz + Atripla. The coinfected patient is a critical patients - coinfected individuals have have markedly increased disease progression far and above that of the monoinfected patient.  Considering that Boceprevir cannot be used in the HIV/HCV coinfected patient, Vertex has this niche all to itself until the 2nd gen compounds prove themselves.  I'm sure these interim results come to the relief of many providers who treat this patient population. 

Data from Phase 2 Study of an INCIVEK® Combination Regimen Showed 74% of People Co-Infected with Hepatitis C and HIV Had Undetectable Hepatitis C Virus 12 Weeks After Treatment Ended (SVR12)

- INCIVEK was well tolerated with commonly used Atripla- and Reyataz-based HIV treatment regimens, and no patients experienced HIV breakthrough -

- Enrollment is ongoing in Phase 3 study evaluating 24- and 48-week treatment durations in people who are co-infected -

SEATTLE--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced interim results from an ongoing Phase 2 study designed to evaluate the safety and tolerability of INCIVEK® (telaprevir) tablets in combination with pegylated-interferon and ribavirin in people who are co-infected with genotype 1 hepatitis C virus and human immunodeficiency virus (HIV). Data showed 74 percent (28/38) of patients who were treated with INCIVEK (in-SEE-veck) combination therapy had undetectable hepatitis C virus (HCV RNA) 12 weeks after the end of all study treatment (SVR12) compared to 45 percent (10/22) who were treated with pegylated-interferon and ribavirin alone. INCIVEK was well tolerated with commonly used Atripla®- and Reyataz®-based HIV treatment regimens. Changes in CD4 counts were similar between the treatment groups and no HIV viral load breakthroughs were observed in either treatment group during the study. The most common adverse events in the INCIVEK arms of the study were fatigue, pruritis (itching), headache, nausea and rash. No cases of severe rash were reported and there were no discontinuations due to rash. Interim results from this study are being presented at the Conference on Retroviruses and Opportunistic Infections (CROI), March 5 to 8, 2012 in Seattle.

"Hepatitis C generally progresses faster, leads to more long-term liver complications and has been harder to cure among people who also have HIV," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "These new INCIVEK data are important as we work toward our goal of helping cure more people with hepatitis C. We're actively enrolling co-infected patients in a Phase 3 study and expect that data from this study will be included in a submission for a supplemental approval of INCIVEK."

The Phase 2 study includes two parts: Part A is evaluating people who are not currently being treated with antiretroviral therapy (ART) for HIV infection and Part B is evaluating those who are taking an Atripla- or Reyataz-based regimen for HIV. This study enrolled patients who were new to hepatitis C treatment (treatment naïve). Patients who were randomized to receive INCIVEK were treated with 12 weeks of INCIVEK, pegylated-interferon and ribavirin, followed by 36 weeks of pegylated-interferon and ribavirin alone. Interim data also showed that 68 percent (26/38) of patients treated with INCIVEK combination therapy in this study had a rapid viral response (RVR, undetectable hepatitis C virus at week 4 of treatment) compared to none (0/22) of the patients who received pegylated-interferon and ribavirin alone.

"There is a great need for treatments that are well tolerated and offer co-infected patients a better chance at a cure for hepatitis C while maintaining suppression of their HIV," said Douglas Dieterich, M.D., Professor of Medicine in the Division of Liver Diseases, Mount Sinai School of Medicine, New York City. "It's very encouraging that nearly three out of four people had undetectable hepatitis C virus 12 weeks after stopping INCIVEK combination therapy and that their HIV medicines continued to work during treatment."

Interim Study Results

Sixty-two people 18 and older were enrolled in this Phase 2 study and 60 received at least one dose of study drug. This analysis was conducted 12 weeks after patients completed all treatment. The ART regimens evaluated in this study were selected based on current HIV treatment guidelines from the U.S. Department of Health and Human Services, International AIDS Society and drug-drug interaction studies of INCIVEK with commonly used ART medicines.

Interim Intent To Treat Analysis of Study #110

Part A (No ART)

Part B Atripla®-based regimen

Part B Reyataz®-based regimen

Total

INCIVEK- based Arm+

Control Arm++

INCIVEK- based Arm+

Control Arm++

INCIVEK- based Arm+

Control Arm++

INCIVEK- based Arm+

Control Arm++

RVR*

71% (5/7)

0% (0/6)

75% (12/16)

0% (0/8)

60% (9/15)

0% (0/8)

68% (26/38)

0% (0/22)

eRVR**

57% (4/7)

0% (0/6)

75% (12/16)

0% (0/8)

47% (7/15)

0% (0/8)

61% (23/38)

0% (0/22)

SVR12

71% (5/7)

33% (2/6)

69% (11/16)

50% (4/8)

80% (12/15)

50% (4/8)

74% (28/38)

45% (10/22)

Atripla-based regimen (efavirenz, tenofovir disoproxil fumarate and emtricitabine): INCIVEK was dosed at 1,125 mg, every 8 hours (q8h).

Reyataz-based regimen (ritonavir-boosted atazanavir, tenofovir disoproxil fumarate and emtricitabine or lamivudine): INCIVEK was dosed at 750 mg, every 8 hours (q8h).

*RVR: Rapid Viral Response; undetectable HCV RNA at week 4.

**eRVR: extended Rapid Viral Response; undetectable HCV RNA at weeks 4 and 12.

+12 weeks of INCIVEK, Pegasys® (PEG, pegylated-interferon alfa-2a) and Copegus® (RBV, ribavirin) followed by 36 weeks of only PEG and RBV.

++48 weeks of PEG and RBV only for hepatitis C treatment.

             
Atripla-based regimen (efavirenz, tenofovir disoproxil fumarate and emtricitabine): INCIVEK was dosed at 1,125 mg, every 8 hours (q8h).

Reyataz-based regimen (ritonavir-boosted atazanavir, tenofovir disoproxil fumarate and emtricitabine or lamivudine): INCIVEK was dosed at 750 mg, every 8 hours (q8h).

*RVR: Rapid Viral Response; undetectable HCV RNA at week 4.
**eRVR: extended Rapid Viral Response; undetectable HCV RNA at weeks 4 and 12.

+12 weeks of INCIVEK, Pegasys® (PEG, pegylated-interferon alfa-2a) and Copegus® (RBV, ribavirin) followed by 36 weeks of only PEG and RBV.
++48 weeks of PEG and RBV only for hepatitis C treatment.

The majority of adverse events in this study were mild or moderate. Adverse events that occurred more frequently in the INCIVEK arms compared to placebo (≥10 percent difference) were pruritis (itching), headache, nausea, rash, fever, and depression. Three patients, all in Arm B, discontinued all study treatment due to adverse events (one each due to gall stones, hemolytic anemia and nausea/vomiting).

About this Phase 2 Study

Vertex and its collaborator Janssen conducted extensive drug-drug interaction studies with INCIVEK and commonly used HIV medicines prior to initiating a development program in people co-infected with hepatitis C (HCV) and HIV. This Phase 2 study is a two-part (A and B), randomized, double-blind, placebo-controlled, parallel group, multi-center study in people chronically infected with both HCV and HIV who were new to HCV treatment. The primary endpoint of the study is to evaluate the safety and tolerability of INCIVEK combination therapy in people co-infected with HCV and HIV. A secondary endpoint is to evaluate rates of sustained viral response (SVR) 12 and 24 weeks after the end of treatment. The study is being conducted by Vertex in collaboration with Janssen.

Phase 3 Study Actively Enrolling

Enrollment is ongoing in a Phase 3 study evaluating 24- and 48-week response-guided regimens of INCIVEK combination therapy in people co-infected with HCV and HIV. Patients who are either new to treatment for HCV, or who had relapsed after at least one prior course of therapy with pegylated-interferon and ribavirin alone, will receive 24 or 48 weeks of INCIVEK combination treatment, based on their antiviral response. Patients who had not responded to a prior course of treatment (partial responders and nulls) will receive 48 weeks of INCIVEK combination treatment. A similar study is also being initiated by Janssen in its territories.

Data from In Vitro Evaluation of INCIVEK and HIV Protease Inhibitors

Also being presented at CROI this week are data from an in vitro evaluation of the anti-HIV activity of four HIV protease inhibitors (amprenavir, darunavir, lopinavir and atazanavir) in combination with INCIVEK. In the study, no antagonistic effects on the antiviral activity were observed when INCIVEK was used in combination with amprenavir, darunavir, and lopinavir, and slight antagonistic effects were observed on the antiviral activity of atazanavir.

About INCIVEK

INCIVEK ® (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK is the most prescribed direct-acting antiviral for the treatment of adults with genotype 1 chronic hepatitis C and has been used to treat more than 30,000 people in the United States.

INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for use in combination with pegylated-interferon and ribavirin for people with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously with interferon-based treatment but who did not achieve a sustained viral response, or viral cure (relapsers, partial responders and null responders).

Vertex developed telaprevir in collaboration with Janssen and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO® in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and is known as Telavic®.

INCIVEK® is a registered trademark of Vertex Pharmaceuticals Incorporated.

PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.

Reyataz® is a registered trademark of Bristol-Myers Squibb.

Atripla® is a registered trademark of Bristol-Myers Squibb and Gilead Sciences, LLC.

About Hepatitis C

Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1

Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 However, approximately 60 percent of people do not achieve SVR,3,4,5 or viral cure,6 after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8

More than 170 million people worldwide are chronically infected with hepatitis C.6 In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.9 Hepatitis C is four times more prevalent in the United States compared to HIV.9 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.10 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.11,12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.9

About Hepatitis C and HIV Co-Infection

There are 1 million people living with HIV in the United States, and an estimated 300,000 people living with HIV/AIDS in the United States are also infected with hepatitis C. 13 There have been dramatic improvements in the treatment of HIV and the prognosis for people living with HIV. However, liver disease progresses more rapidly in people co-infected with hepatitis C and HIV, with an increased rate of progression to cirrhosis, decompensated liver disease, hepatocellular carcinoma and death. 14, 15, 16, 17 The hepatitis C cure rate with a 48-week treatment of pegylated-interferon and ribavirin, the current standard of care for people with co-infection, is approximately 29 percent.18

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis, epilepsy and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and Science magazine named Vertex number one on its 2011 list of Top Employers in the life sciences.

Vertex's press releases are available at www.vrtx.com.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including Dr. Kauffman's statements in the second paragraph of this press release and statements regarding ongoing and planned Phase 3 studies of INCIVEK combination therapy in people co-infected with HCV and HIV. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the outcomes from future clinical trials of INCIVEK combination therapy in co-infected patients may not be favorable and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

IMPORTANT SAFETY INFORMATION

Indication

INCIVEK® (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.

Important Safety Information

INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines. Hormonal forms of birth control, including birth control pills, vaginal rings, implants or injections, may not work during treatment with INCIVEK.

INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.

INCIVEK can cause serious side effects including skin reactions, rash and anemia that can be severe. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.

Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com.

(VRTX-GEN)

References:

1 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed February 22, 2012.

2 Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.

3 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.

4 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.

5 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.

6 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

7 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).

8 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

9 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed February 22, 2012.

10 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. Available at: http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. Accessed February 22, 2012. This report was commissioned by Vertex Pharmaceuticals, Inc.

11 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.

12 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.

13 HIV Advocate. HIV/HCV Coinfection. Available at: http://www.hcvadvocate.org/hepatitis/factsheets_pdf/HIV_HCV20coinfecton_10.pdf. Accessed February 28, 2012.

14 Martin-Carbonero L, Benhamou Y, Puoti M, Berenguer J, Mallolas J, Quereda C, et al. Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study. CID 2004;38:128-33.

15 Martinez-Sierra C, Arizcorreta A, Diaz F, Roldan R, Martin-Herrera M, Perez- Guzman E, et al. Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus. CID 2003;36:491-8.

16 Matthews GV, Dore GJ. HIV and hepatitis C coinfection. JGH. 2008; 23: 1000-1008.

17 Bruno R, Sacchi P, Puoti M, Soriano V, Filice G. HCV chronic hepatitis in patients with HIV: clinical management issues Am J Gastroenterol 2001; 97:1598—1606.

18 Levin, J. Pegasys/RBV in APRICOT Study- Adherence Improves SVR 300% in genotype 1. Available at: http://www.natap.org/2005/ICAAC/icaac_31.htm Accessed February 28, 2012.



Vertex Pharmaceuticals Incorporated

Media:

Dawn Kalmar
Erin Emlock
Zach Barber
617-444-6992
mediainfo@vrtx.com

or

Investors:
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or
Lora Pike, 617-444-6755

Source: Vertex Pharmaceuticals Incorporated

News Provided by Acquire Media

Merck releases 24 week Boceprevir interim Phase IIb data in HIV/HCV co-infected patients...

Twenty-four week interim Phase IIb results looking a Boceprevir + PR in HIV/HCV co-infected patients. Results at week 24 show 70.5% (n=43/61) of patients receiving bocepreivr + PR were undetectable compared to 34.4%(n=11/32) of patients receiving just PR alone. This represented a treatment difference of 36.1%, according to the press release. Not much is said about the HIV regimen patients were on, other than it didn't include AZT or any of the 'D' drugs. Because boceprevir is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5, drug-drug interactions with HIV antivirals are a real possibility. Merck also announced a trial in co-infected subjects who had failed previous therapy in conjunction with the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) as well as a Phase III coinfection study in collaboration tithe the AIDS Clinical Trials Group (ACTG).

Interim Phase IIb Data for Merck's VICTRELIS(TM) (boceprevir) in Patients Coinfected with Chronic Hepatitis C and HIV-1 Presented at the Infectious Diseases Society of America (IDSA) 2011 Annual Meeting

BOSTON, Oct 20, 2011 (BUSINESS WIRE) -- Merck, known as MSD outside of the United States and Canada, today announced results from a 24-week interim analysis of an ongoing 48-week Phase IIb clinical study evaluating the investigational use of VICTRELIS(TM) (boceprevir), the company's first-in-class, oral hepatitis C virus (HCV) NS3/4A protease inhibitor, in combination with peginterferon alfa and ribavirin for the treatment of chronic HCV genotype 1 infection in adult patients coinfected with HIV-1. All patients in the study were new to treatment for chronic HCV, on an optimized antiretroviral regimen and had stable HIV-1 disease. The interim analysis showed that at week 24 of treatment, 70.5 percent (n=43/61) of patients receiving VICTRELIS in combination with peginterferon alfa-2b and ribavirin had undetectable hepatitis C virus (HCV-RNA) compared to 34.4 percent (n=11/32) of patients receiving peginterferon alfa-2b and ribavirin alone, a treatment difference of 36.1 percent. These interim results are being presented for the first time in a late-breaker oral presentation at the Infectious Diseases Society of America (IDSA) 2011 annual meeting in Boston. Final results from the study are expected in 2012.

"We are encouraged by these interim results with VICTRELIS in combination therapy in this difficult-to-treat patient population," said Roger J. Pomerantz, M.D., F.A.C.P., senior vice president, Infectious Diseases, Merck Research Laboratories. "Helping patients who are dealing with both chronic hepatitis C and HIV-1 is a critical issue in infectious diseases today, and Merck is committed to evaluating VICTRELIS in these patients. In addition to this ongoing Phase IIb study in patients new to HCV treatment, we are collaborating with the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) on an ongoing Phase II study in patients who failed previous HCV treatment. We also plan to begin a Phase III coinfection study for VICTRELIS in combination therapy later this year in collaboration with the AIDS Clinical Trials Group (ACTG), which is funded by the U.S. National Institute of Allergy and Infectious Diseases."

Indications and usage for VICTRELIS

VICTRELIS was approved by the U.S. Food and Drug Administration (FDA) on May 13 for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients (18 years of age and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.

The following points should be considered when initiating VICTRELIS for treatment of chronic hepatitis C infection:

-- VICTRELIS must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin.

-- VICTRELIS efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that includes VICTRELIS or other HCV NS3/4A protease inhibitors. VICTRELIS in combination with peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2 log HCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included patients who were poorly interferon responsive. Patients with less than 0.5 log HCV-RNA decline in viral load at treatment week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than a 2 log HCV-RNA decline by treatment week 12) to peginterferon alfa and ribavirin therapy.

-- Poorly interferon responsive patients who were treated with VICTRELIS in combination with peginterferon alfa and ribavirin have a lower likelihood of achieving a sustained virologic response (SVR), and a higher rate of detection of resistance-associated substitutions upon treatment failure, compared to patients with a greater response to peginterferon alfa and ribavirin.

Key interim results

One hundred (100) adult patients with previously untreated HCV genotype 1 infection and stable HIV-1 disease (HIV-RNA less than 50 copies/mL; CD4 cell counts equal to or greater than 200 cells/mm(3)) were randomized into the study. Two patients randomized to the treatment arm receiving VICTRELIS in combination with peginterferon alfa-2b (P) and ribavirin (R) did not receive VICTRELIS. Thus, the interim analysis was based on 98 patients who received at least one dose of study drug: 64 patients in the arm receiving VICTRELIS plus P/R, and 34 patients in the control arm receiving P/R alone. All patients treated in the study received a 4-week lead-in with P/R alone followed by VICTRELIS plus P/R or placebo plus P/R for 44 weeks, for a total treatment duration of 48 weeks.

Preliminary safety data for VICTRELIS in combination therapy in HCV/HIV coinfected patients demonstrated a profile similar to that previously observed in patients with HCV mono-infection. There were no unexpected trends in HIV-RNA levels or CD4 cell counts.

The most common clinical adverse events with a difference of equal to or greater than 10 percent for the treatment arm receiving VICTRELIS plus P/R compared to the P/R control arm, respectively, were: neutropenia (13 vs. 3 percent), dysgeusia (bad taste) (25 vs. 15 percent), vomiting (25 vs. 15 percent), pyrexia (34 vs. 21 percent), headache (28 vs. 12 percent) and decreased appetite (30 vs. 18 percent) [median days on study, 211 vs. 166, respectively]. Serious clinical adverse events occurred in 8 percent and 21 percent of patients in the two treatment arms, respectively. Dose modification for any study drug due to a clinical adverse event occurred in 19 percent and 21 percent of patients, respectively, and study discontinuation due to a clinical adverse event occurred in 14 percent and 9 percent of patients, respectively.

About the Phase IIb coinfection study

The primary objective of this ongoing randomized, multicenter, double-blinded for VICTRELIS, Phase IIb study is to compare the efficacy of VICTRELIS 800 mg three times daily in combination with peginterferon alfa-2b (P) 1.5 mcg/kg weekly plus ribavirin (R) 600 to 1,400 mg daily to therapy with P/R alone in adult patients coinfected with chronic HCV genotype 1 and HIV-1. Patients were randomized in a 2:1 ratio to the treatment arm with VICTRELIS plus P/R or the P/R control arm, respectively. Patients were stratified by cirrhosis (yes/no) and baseline HCV-RNA (less than 800,000 IU/mL vs. equal to or greater than 800,000 IU/mL). The majority of patients were non-cirrhotic (95 percent), white (82 percent) and male (69 percent), with a median age of about 43 years. Most patients had high HCV-RNA (88 percent) at baseline and HCV genotype 1a infection (65 percent).

Antiretroviral regimens for HIV-1 that included non-nucleoside reverse transcriptase inhibitors (NNRTIs), zidovudine, stavudine or didanosine were not permitted. Patients with detectable HCV-RNA and less than a 2 log HCV-RNA decline at treatment week 12 or detectable HCV-RNA at treatment week 24 were considered treatment failures and discontinued all treatment.

Important safety information about VICTRELIS

All contraindications to peginterferon alfa and ribavirin also apply since VICTRELIS must be administered with peginterferon alfa and ribavirin. Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with peginterferon alfa and ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant. Avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to therapy; have monthly pregnancy tests; and use two or more forms of effective contraception, including intrauterine devices and barrier methods, during treatment and for at least 6 months after treatment has concluded. Systemic hormonal contraceptives may not be as effective in women while taking VICTRELIS.

VICTRELIS is contraindicated in coadministration with drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events. VICTRELIS also is contraindicated in coadministration with potent CYP3A4/5 inducers where significantly reduced boceprevir plasma concentrations may be associated with reduced efficacy. Drugs that are contraindicated with VICTRELIS include: alfuzosin, carbamazepine, phenobarbital, phenytoin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John's Wort (hypericum perforatum), lovastatin, simvastatin, drosperinone, Revatio(R) (sildenafil) or Adcirca(R) (tadalafil) (when used for the treatment of pulmonary arterial hypertension), pimozide, triazolam, and midazolam (orally administered).

Anemia has been reported with peginterferon alfa and ribavirin therapy. The addition of VICTRELIS to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations. The addition of VICTRELIS may result in a worsening of neutropenia associated with peginterferon alfa and ribavirin alone. Complete blood count (with white blood cell differential counts) must be conducted in all patients prior to initiating VICTRELIS combination therapy. Complete blood counts should be obtained pretreatment, and at treatment weeks 4, 8 and 12, and should be monitored closely at other time points, as clinically appropriate. If a patient has a serious adverse reaction potentially related to peginterferon alfa and ribavirin therapy, the peginterferon alfa and/or ribavirin dose should be reduced or discontinued. VICTRELIS must not be administered in the absence of peginterferon alfa and ribavirin. Dose reduction of VICTRELIS is not recommended.

The most commonly reported adverse reactions (greater than 35 percent) in clinical trials in adult patients receiving the combination of VICTRELIS with peginterferon alfa-2b and ribavirin were fatigue, anemia, nausea, headache and dysgeusia. Of these commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates greater than or equal to 5 percent above the rates for peginterferon alfa and ribavirin alone in either clinical study. The incidence of these adverse reactions in previously untreated patients who received VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (58 vs. 59 percent), anemia (50 vs. 30 percent), nausea (46 vs. 42 percent), dysgeusia (35 vs. 16 percent), respectively. The incidence of these adverse reactions in previously treated patients who received VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (55 vs. 50 percent), anemia (45 vs. 20 percent), nausea (43 vs. 38 percent), dysgeusia (44 vs. 11 percent), respectively.

VICTRELIS is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5. The potential for drug-drug interactions must be considered prior to and during therapy.

Please see U.S. prescribing information at: http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf .

Merck's global commitment to advancing hepatitis therapy

Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. In hepatitis C, company researchers developed the first approved therapy for chronic HCV in 1991 and the first combination therapy in 1998. In addition to ongoing studies with VICTRELIS, extensive research efforts are underway to develop additional innovative oral therapies for viral hepatitis treatment.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Forward-Looking Statement

This news release includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company's plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck's management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.

The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck's ability to accurately predict future market conditions; dependence on the effectiveness of Merck's patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck's 2010 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site ( www.sec.gov ).

Please see Prescribing Information for VICTRELIS at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf and Medication Guide for VICTRELIS at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_mg.pdf .

SOURCE: Merck


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Sexual transmission of HCV virus more prevalent than previously thought....

(From the LA Times 'Booster Shots' blog, July 21, 2011. This type of thing isn't usually fare for the purposes of this group but I think it is significant in a couple of different ways - first, sexual transmission of the HCV virus is still inefficient, but it happens more than we previously though. Second, this opens up the possibility that transmission of fit drug resistant variants of the virus may be possible which is of major concern, especially in the HIV/HCV co-infected population where the progression of the disease is much more rapid. Currently, there is no sequential therapy for HCV and not likely to be until late 2013. - Chris)


By Thomas H. Maugh II, Los Angeles Times/For the Booster Shots blog
July 21, 2011, 11:12 a.m.

The hepatitis C virus, normally thought to be transmitted exclusively through blood — such as by sharing of needles among intravenous drug abusers — can also be transmitted through sexual activity, principally through anal sex among gay men, a growing body of evidence suggests. The most recent evidence was reported Thursday by New York City researchers who documented an outbreak of the virus, commonly known as HCV, among gay men.

Hepatitis C, which can cause severe liver disease and even death if left untreated, affects an estimated 3.2 million Americans. Many infected people show no symptoms, but others have severe disease that can require liver transplants. The infection can be cured in most people with a combination of the drugs pegylated interferon alpha and ribavirin, plus a recently approved drug called Incivek, but treatment is most successful when started early in the course of the disease.

Dr. Daniel Fierer, an infectious diseases expert at the Mount Sinai School of Medicine, and his colleagues first observed two cases of HCV that they believed to be caused by sexual transmission in late 2005. They requested referrals of similar patients. The team reported Thursday in the Centers for Disease Control and Prevention's Morbidity and Mortality Weekly Report that they found a total of 74 cases. All the men reported having receptive anal sex and none had any other risk factors for HCV, such as intravenous drug abuse. When the team compared the infected men to other gay men who were not infected with the virus, they found that those who became infected were 23 times more likely to have had unprotected gay sex and 29 times more likely to have had anal sex while using crystal methamphetamine. Moreover, genetic analysis showed that there were five separate clusters of the virus, indicating that the virus was getting transmitted through groups of interconnected men.

"While hepatitis C is not sexually transmitted among stable heterosexual couples, this is clearly not the case among HIV-infected [men having sex with men] in New York City," Fierer said in a statement. Such men, "and to some extent their healthcare providers, are generally not aware that having unprotected receptive sex can result in HCV infection .... Our study suggests that HIV-infected [gay men] should take steps to protect themselves and others by using condoms and by avoiding crystal methamphetamine."

HIV Physicians Are Cautiously Optimistic About Boceprevir, Telaprevir For HIV-HCV Co-Infected Patients

Courtney McQueen from The AIDS Beacon, interviews Dr. Kenneth Mayer from Brown University's HIV program and Dr. Bruce Bacon ce Bacon,co-director of the Liver Center at St. Louis University Medical School on the use of Telaprevir and Boceprevir in co-infected patient. It appears both are cautiously hopeful about the use of either drugs in the co-infected setting, but need to fully understand the ramifications of the final data set, that should arrive in June 2012 for telaprevir and November 2012 for boceprevir. The largest cause for caution are the known drug interactions with many of the currently marketed antiretrovirals


HIV Physicians Are Cautiously Optimistic About Boceprevir, Telaprevir For HIV-HCV Co-Infected Patients
By Courtney McQueen
Published: May 6, 2011 6:02 pm

Last week an advisory panel to the U.S. Food and Drug Administration recommended that boceprevir and telaprevir be approved for the treatment of hepatitis C. For people with HIV and hepatitis C co-infection, the new drugs are an exciting development; however, a number of studies still need to be completed before the drugs are considered for people with HIV.

“It has the potential to revolutionize care, but I think it’s just the beginning of the journey,” said Dr. Kenneth Mayer, a professor of medicine at Brown University, director of the Brown University AIDS Program, and medical research director at Fenway Community Health. Dr. Mayer was not involved with development of either of the drugs.

Dr. Mayer, who has been seeing HIV and AIDS patients since the beginning of the epidemic, thought the early results for both drugs are promising. However, he also thought a lot more research needs to be done before clinicians can feel comfortable prescribing the drugs to people with HIV.

“The vast majority of the studies so far are in mono-infected individuals [people with hepatitis C only], so I think there’s a bunch of questions that have to be answered before we’re sure of how to use these drugs best for people with HIV,” he said.

If the Food and Drug Administration (FDA) approves the drugs, they could be available to patients as soon as late May. Although the FDA is not required to follow the recommendations of its advisory committees, it usually does.

For People With HIV, Boceprevir And Telaprevir Clinical Trials Are Still In Early Stages

The approval recommendations from last week are based on Phase 3 clinical trials in people infected only with hepatitis C virus (HCV). The trials showed that adding boceprevir or telaprevir to standard HCV treatment raised cure rates from about 40 to 45 percent to about 65 to 80 percent.

Standard HCV treatment consists of 48 weeks of ribavirin (Rebetol, Copegus) plus Pegasys (pegylated interferon alfa-2a) or PegIntron (pegylated interferon alfa-2b). Typically, standard HCV treatment is less effective in people who are also infected with HIV (see related AIDS Beacon news).

For people with HIV, the benefits of the new drugs are not clear yet. Both drugs are currently in Phase 2 clinical trials for people who are co-infected with HIV and HCV, with estimated trial completion dates of June 2012 for telaprevir and November 2012 for boceprevir.

Dr. Bruce Bacon, a professor of internal medicine and co-director of the Liver Center at St. Louis University Medical School, was involved in clinical trials for both drugs and expressed optimism about their success in co-infected patients.

“Definitely the cure rates, or sustained virologic response, for co-infected patients will be significantly improved with either boceprevir or telaprevir. How much they will be improved, I don’t know yet,” he said.

Preliminary results for telaprevir were presented in March at the Conference on Retroviruses and Opportunistic Infections (see related AIDS Beacon news). Results at that time were promising; 70 percent of HIV-HCV patients receiving telaprevir in addition to standard therapy of ribavirin and Pegasys had undetectable HCV levels after four weeks, compared to 5 percent of patients receiving the placebo plus standard therapy.

Among the participants who received telaprevir for 12 weeks, 68 percent had undetectable HCV levels, compared to 14 percent of participants receiving ribavirin plus Pegasys alone. However, not all participants had reached 12 weeks of treatment by the time of the analysis.

Additionally, overall hepatitis C cure rates were not yet available. Clinicians consider a patient to be cured of hepatitis C if the virus remains undetectable for 24 weeks after stopping treatment (called a sustained virologic response).

Dr. Bacon stated that the telaprevir results should be taken with caution. “That’s pretty early data. I think it’s probably a little too early to know the significance of [the telaprevir results],” he said.

Results for boceprevir in people who are HIV-HCV co-infected are not yet available.

For people with HIV-HCV co-infection, the lack of definitive results means that some patients may need to decide whether to take the drugs when they become available, or wait until the clinical trials are complete and physicians have more information on the drugs’ efficacy and safety in people with HIV.

“If a person is not in acute need of treatment, it may be prudent to wait, to know how to best manage [treatment],” said Dr. Mayer.

“The initial guidelines will not recommend these drugs for co-infected people until there is more data, so there would also be a question of whether third party payers or insurers would reimburse for the cost of the medications, and I’m sure that the cost of the medications would be considerable,” he added.

Dr. Bacon stated that he was likely to start prescribing the drugs without waiting for all of the clinical trial results. “I have a large number of co-infected patients who are waiting for treatment, and I’m probably not going to wait until the results of all the studies are done. But I do need to make sure that I find out about the drug-drug interaction issues,” he said.

More Data Needed On Drug Interactions, Safety In People With HIV

Both Dr. Mayer and Dr. Bacon agreed that one of the main concerns for people with HIV will be the safety of the drugs and whether they interact with HIV medications.

“I’m hoping that there will be a very robust program of research for dually infected individuals, so we can get a better sense of the expanded safety profile of these drugs,” said Dr. Mayer.

Both boceprevir and telaprevir have associated side effects, such as anemia and rash (see related AIDS Beacon news). The Phase 2 trials in co-infected people should demonstrate whether these side effects are more common or more severe in people with HIV.

In addition, the clinical trials that are underway for both drugs will monitor how they interact with common HIV antiretrovirals. For example, researchers will test whether the hepatitis C drugs affect the concentrations of antiretrovirals in the bloodstream – either decreasing them, which would make them less effective against HIV, or increasing them, which could cause greater side effects.

They will also test whether the antiretrovirals, in turn, affect the hepatitis C drugs and their efficacy. If drug interactions are found, dosages of either the hepatitis C drugs or certain antiretrovirals may need to be adjusted for people with HIV.

For telaprevir, there are some preliminary indications that there might be interactions with certain antiretrovirals, namely protease inhibitors boosted with Norvir (ritonavir). It is not clear yet whether these will require dosage adjustments of either telaprevir or the protease inhibitors in patients taking these drugs.

No information is available yet on drug interactions for boceprevir.

People With HIV Should Get Tested – And Retested – For Hepatitis C

With the two new drugs potentially available in the near future, both physicians urged people with HIV to get tested for HCV so they can start treatment if necessary.

“This underscores the importance of everybody who’s HIV infected to know their hepatitis C status. If somebody has engaged in any behaviors that might put them at risk for acquiring hepatitis C, they should be retested,” said Dr. Mayer.

“Even if somebody is not going to start these medications tomorrow, we are getting into the mode where, fairly soon, we’ll be able to start treating hepatitis C earlier,” he added.

Hepatitis C is spread in much the same way as HIV – unprotected sexual intercourse, sharing of needles, and other exposures to infected bodily fluids.

Dr. Bacon said patients who are co-infected should not avoid treatment.

“If they do know that they’re co-infected, they should know that there’s something that will be better than what there used to be. They ought to see a specialist who is knowledgeable about [the new drugs], and they ought to be treated,” said Dr. Bacon.

“I think it’s a new era for hepatitis C patients, and it will be a new era for co-infected patients as well,” he added.

Next Steps For Hepatitis C Treatment

Researchers have already begun to discuss the next phases of hepatitis C treatment. Both Dr. Mayer and Dr. Bacon were optimistic about the future for people with hepatitis C and HIV-HCV co-infection.

“Hopefully in the next few years we’ll be in the position to have a lot of different choices, much in the same way that we have for HIV,” said Dr. Mayer.

Dr. Bacon agreed. “Most people feel that there will be new regimens that are going to be used, and both telaprevir and boceprevir, as first generation protease inhibitors, will be replaced by second and third generation drugs and different regimens. Hopefully interferon-free regimens,” he said.

Interferon (Pegasys or PegIntron), which is part of the current standard treatment regimen for hepatitis C, is difficult to take (it must be injected, usually once a week) and is associated with many side effects.

“I think we’re within a couple of years of having large studies with non-interferon based treatment that will be successful,” said Dr. Bacon.

Original article: http://www.aidsbeacon.com/news/2011/05/06/hiv-aids-physicians-are-cautiously-optimistic-about-boceprevir-telaprevir-for-hiv-hcv-co-infected-patients/

Jurgen Rockstroh comments HCV/HIV coinfection in the era of Direct Acting Antivirals...

Jurgen K. Rockstroh M.D., Professor of Medicine University of Bonn, Germany, gives us a synopsis of what the new DAAs for Hepatitis C will mean for patients with HIV/HCV coinfection. I highly recommend a full read through, Dr. Rockstroh walks through the latest efficacy, resistance and drug -drug interaction data on Boceprevir and Telaprevir as well as current epidemiological patterns in the disease state . We'll need SVR data from both drugs to make a full assessment, but from the interim 12 week data, it appears Telaprevir is very effective at reducing HCV viral load in the coinfected patient, although there are some serious drug-drug interactions to look out for as well as a higher incidence of adverse events. Read the entire article here

Vertex shows Telaprevir RVR data in HIV/HCV co-infected subjects...

Press release from Vertex regarding RVR rate in treatment naive co-infected subjects. Good RVR rates in subjects on both Atripla and boosted Atazanavir (and ? backbone. 'N' is small and of course you'd never treat HCV in someone that wasn't already stable on HIV therapy, but looks promising in those that haven't any resistance to Atripla components and Atazanavir plus whatever backbone regimen was used.

UPDATE 1-Vertex drug promising in hep C patients with HIV
1:06pm EST
* RVR rate 70 pct with telaprevir combination therapy
* RVR rate 5 pct on standard hepatitis C drugs alone
* Vertex expects final cure rate data in 2012

By Bill Berkrot

NEW YORK, March 2 (Reuters) - Vertex Pharmaceuticals Inc's (VRTX.O: Quote, Profile, Research, Stock Buzz) hepatitis C drug telaprevir helped eliminate the virus in 70 percent of patients who were also infected with HIV, according to interim analysis from a small midstage clinical trial, the company said.

Telaprevir is awaiting a U.S. approval decision after demonstrating an ability to greatly improve hepatitis cure rates when combined with current standard of care medicines compared with those drugs alone.

Patients in the co-infection study, which was presented at a medical meeting on Wednesday, had not yet received other treatment for hepatitis. Telaprevir was tested in one group of patients who were not receiving antiretroviral therapy for HIV and another group who were.

The interim analysis looked for a rapid viral response (RVR), meaning the hepatitis C virus was undetectable in the blood after four weeks of treatment.

At four weeks, 70 percent of those in the 60-patient study who received combination therapy with telaprevir had achieved RVR compared with 5 percent who received only the standard drugs of pegylated interferon and ribavirin, according to data presented at the Conference on Retroviruses and Opportunistic Infections in Boston.

Undetectable virus must be maintained for a far longer period of time in order to achieve sustained viral response (SVR), which is tantamount to a cure. But RVR can be an early indicator of eventual success rates.

SVR rates from the study are expected to be available next year, Vertex said.

In patients who were not also receiving HIV antiretroviral therapy, 71 percent of those treated with telaprevir achieved RVR compared with none on the standard drugs.

For co-infected patients taking Gilead Sciences Inc's Atripla for HIV, 75 percent on telaprevir combination therapy hit RVR versus one patient, or 13 percent, in the control arm.

For HIV patients being treated by Bristol-Myers Squibb's Reyataz, 64 percent on telaprevir hit RVR versus no one in the eight-patient control arm.

Vertex shares were up $1.12, or 2.4 percent, at $47.17 in afternoon trade on Nasdaq. (Reporting by Bill Berkrot, editing by Dave Zimmerman)