CAMBRIDGE, Mass.–(BUSINESS WIRE)– Vertex Pharmaceuticals Incorporated (NASDAQ: VRTX) today announced interim data from two treatment arms of the Phase 2 ZENITH study evaluating an interferon-free (all-oral) treatment regimen of the non-nucleoside polymerase inhibitor VX-222 in combination with INCIVEK ® (telaprevir) tablets and ribavirin in people with genotype 1a or 1b hepatitis C who were new to treatment. Interim data showed that viral loads were below the lower limit of quantification ( < 25 IU/mL: < LLOQ) for 80 percent (37/46) of patients with genotype 1 hepatitis C at week two and 83 percent (38/46) of patients with genotype 1 at week 12.
ZENITH was designed with strict response-guided criteria that determined whether a patient was eligible to stop all treatment at 12 weeks. Eleven patients met the criteria of having undetectable hepatitis C virus at weeks two and eight of treatment and were therefore eligible to stop all treatment at 12 weeks. Nine of these 11 patients achieved SVR4 (undetectable hepatitis C virus four weeks after the end of all treatment). Data from ZENITH have been submitted for presentation at a medical meeting in the first half of 2012.
Additional interim results from two interferon-free arms of ZENITH announced today showed:
Arm E† (n=23)
Arm F‡ (n=23)
Arms E & F
|6/23 (26%)||7/23 (30%)||13/46 (28%)|
|< LLOQ**||21/23 (91%)||16/23 (70%)||37/46 (80%)|
|Week 4 (RVR)||
|21/23 (91%)||13/23 (57%)||34/46 (74%)|
|< LLOQ||21/23 (91%)||21/23 (91%)||42/46 (91%)|
|Week 12 (cEVR)||
|19/23 (83%)||19/23 (83%)||38/46 (83%)|
|< LLOQ||19/23 (83%)||19/23 (83%)||38/46 (83%)|
|5/5||Data not yet available||Data not yet available|
| † 19 patients completed 12 weeks of treatment: Two patients discontinued due to adverse events. One patient had virologic failure. One patient withdrew consent.
‡ 20 patients completed 12 weeks of treatment. Two patients had virologic failure. One patient was lost to follow up.
* HCV RNA < 10 IU/mL
** HCV RNA < 25 IU/mL
^ The two patients who did not achieve SVR4 relapsed during the post-treatment follow-up period.
The three drug regimen was generally well-tolerated. The majority of adverse events were reported as mild. There were no cases of moderate or severe rash and no discontinuations due to rash or anemia in the interferon-free study arms. There were two discontinuations due to adverse events in the genotype 1b arm of the study.
Vertex Advances INCIVEK, VX-222 and Ribavirin Combination Regimen
Based on these data, and pending discussions with regulatory agencies, the company intends to pursue a Phase 2b study evaluating multiple interferon-free combination regimens of INCIVEK, VX-222 and ribavirin with total treatment durations as short as 12 weeks in people with genotype 1 (1a and 1b) hepatitis C who are new to treatment. The new study will not use response-guided treatment criteria. If successful, data from this study will be used to design a Phase 3 program with the goal of submitting a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Vertex’s first interferon-free regimen for genotype 1 (1a and 1b) patients by the end of 2014 or beginning of 2015, pending regulatory discussions.
“Since its approval INCIVEK has been used to treat tens of thousands people with hepatitis C and we’re committed to further improving the care of those living with this disease by evaluating multiple interferon-free regimens,” said Peter Mueller, Ph.D., Executive Vice President, Global Research and Development, and Chief Scientific Officer for Vertex. “Our ultimate goal is to develop well-tolerated, interferon-free treatment regimens with high viral cure rates and short treatment durations for people with hepatitis C. We believe we’re well-positioned to achieve this goal by exploring various combinations within our portfolio that includes INCIVEK, VX-222 and two structurally-distinct nucleotide polymerase inhibitors.”
Advancing Development of Two Nucleotide Polymerase Inhibitors
As part of a broad strategy to develop interferon-free regimens, Vertex and its collaborator Alios BioPharma are conducting Phase 1 studies of two structurally-distinct nucleotide polymerase inhibitors, known as ALS-2200 and ALS-2158. Vertex announced today that it has begun the first 7-day viral kinetic studies of ALS-2200 and ALS-2158 in people with genotype 1 hepatitis C. Safety and viral kinetic data from these studies are expected in the second quarter of 2012, which could enable the initiation of Phase 2 studies in the second half of 2012 to evaluate multiple interferon-free combination regimens of ALS-2200, ALS-2158, INCIVEK, VX-222 and/or ribavirin.
ZENITH is an ongoing Phase 2 study that enrolled 152 people with genotypes 1a and 1b chronic hepatitis C who had not been previously treated to evaluate multiple response-guided treatment regimens with VX-222, Vertex’s non-nucleoside polymerase inhibitor in development, in different combinations with INCIVEK, Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin), three medicines approved to treat hepatitis C. In all arms, patients were eligible to stop all treatment at 12 weeks if they had undetectable hepatitis C virus at weeks 2 and 8. The primary endpoint of the study is safety and tolerability. The secondary endpoint is on-treatment antiviral activity and the proportion of people in each treatment arm who achieve a sustained viral response.
About INCIVEK and VX-222
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 25,000 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 Tibotec BVBA 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). Through its affiliate, Janssen, Tibotec 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®.
VX-222 is an oral medicine in development that is a non-nucleoside inhibitor of the HCV NS5B polymerase. Vertex has worldwide commercial rights for VX-222.
About ALS-2200 and ALS-2158
ALS-2200 and ALS-2158 are nucleotide analogues that appear to have a high barrier to drug resistance based on non-clinical and in vitro studies. Both compounds are designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. Each compound is structurally distinct (adenosine and uracil) and has its own unique mechanism of action, which supports the potential for developing these compounds together as a dual nucleotide regimen and as part of combination therapy regimens, including regimens with INCIVEK and VX-222. Data from in vitro studies showed that both ALS-2200 and ALS-2158 had a synergistic effect when combined together and with INCIVEK and VX-222.
Additionally, in vitro studies of both compounds showed antiviral activity across all genotypes, or forms, of the hepatitis C virus, including genotypes more prevalent outside of the United States.
Vertex gained worldwide rights to ALS-2200 and ALS-2158 through an exclusive worldwide licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that will focus on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.
You might be aware that FDA plays a key role in assuring the safety and efficacy of products such as drugs, vaccines and foods. But less well known is the agency’s critical regulatory oversight of our nation’s blood supply.
Blood saves and improves the lives of millions of individuals each year. It is used for transfusions for example, to replace blood loss during surgery, childbirth or following a traumatic injury. Blood and blood products are also a key part of the medical treatment of serious illnesses such as cancer, organ failure, or sickle cell disease. Additionally, blood and blood products are used to prevent and treat many medical conditions, such as infections and blood clotting disorders.
Transient Elastography Offers Non-invasive Diagnostic for Detecting Severe Fibrosis
Researchers from the Mayo Clinic confirm that ultrasound-based transient elastography (TE) provides excellent diagnostic accuracy for detecting cirrhosis due to recurrent infection with hepatitis C virus (HCV) infection following liver transplantation. Findings from the study published in the March issue of Liver Transplantation, a journal of the American Association for the Study of Liver Diseases, suggest that detection of significant fibrosis is more accurate when comparing patients with chronic HCV of the native liver.
According to the World Health Organization (WHO), chronic HCV affects up to 170 million people worldwide and could lead to more severe liver diseases such as cirrhosis and liver cancer. Experts estimate that on average 6,000 liver transplants are performed in the U.S. each year. Medical evidence shows that following liver transplantation recipients who are HCV RNA-positive at the time of transplantation are at risk of reinfection with HCV. Moreover, studies have determined that fibrotic tissue can develop more quickly in the transplanted liver resulting in rapid progression of cirrhosis and graft failure.
“The current gold standard for determining liver disease severity and progression is liver biopsy,” explains lead author Dr. Jayant Talwalkar with the Mayo Clinic in Rochester, Minnesota. “However, biopsy following liver transplantation may not accurately determine fibrosis severity and non-invasive imaging technology has advanced to more accurately assess the severity of liver injury which includes an indirect assessment of elevated portal pressure.” A prior study reported liver biopsy can understage cirrhosis in up to 30% of cases.
For the present study researchers reviewed studies of the diagnostic accuracy of ultrasound-based TE, a non-invasive technology used to assess fibrosis by measuring liver stiffness. The team analyzed the performance of TE compared to liver biopsy in detecting sever hepatic fibrosis caused by recurrent HCV post-transplantation. Compared to liver biopsy, TE is a reproducible diagnostic technique that is quick and painless for patients.
Six studies were identified, with five studies that evaluated significant fibrosis and cirrhosis. Analysis of the pooled estimates showed TE had a sensitivity and specificity of 83%, respectively for detecting fibrosis. Of the five studies analyzing TE for detecting cirrhosis, sensitivity estimates were 98% and specificity at 84%. “Ultrasound-based TE provides excellent diagnostic accuracy for identifying cirrhosis caused by recurrent HCV following liver transplantation,” concludes Dr. Talwalkar. “Further studies that confirm our results could highlight the importance of TE as a diagnostic tool for liver transplant recipients infected with HCV.”
Author Contact: To arrange an interview with Dr. Talwalkar please contact Brian Kilen with the Mayo Clinic at Kilen.Brian@mayo.edu or 507-266-1161.
About the Journal
Liver Transplantation. is published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Since the first application of liver transplantation in a clinical situation was reported more than twenty years ago, there has been a great deal of growth in this field and more is anticipated. As an official publication of the AALSD and the ILTS, Liver Transplantation. delivers current, peer-reviewed articles on surgical techniques, clinical investigations and drug research — the information necessary to keep abreast of this evolving specialty. For more information, please visit Liver Transplantation.
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The World Hepatitis Alliance newsletter is available for download in any of the seven languages used by the Alliance at: http://www.worldhepatitisalliance.org/Community_Map/Newsletter.aspx.
Using a computer model of the hepatitis C disease, Stanford researchers have shown that two new drugs intended to target the virus are cost-effective for patients suffering from advanced hepatitis C, despite some significant side effects.
Hepatitis C, a virus that leads to swelling or inflammation of the liver, is now killing more Americans than the HIV virus. The majority of the 3.2 million people estimated to have chronic hepatitis C in the United States are baby-boomer adults, according to a Scientific American blog.
Implementing DAA Therapy in Practice
LITTLE FALLS, N.J., Feb. 23, 2012 /PRNewswire/ — Projects In Knowledge (PIK) has released its free point-of-care HCV Care & Guidance iPhone/iPad app, giving clinicians mobile access to this widely used, dynamic practice tool.
HCV Care & Guidance provides peer-reviewed, practical education about direct-acting antiviral (DAA) therapies, an exciting new treatment option for patients with hepatitis C virus (HCV) infection. Nurses/NPs, physician assistants, gastroenterologists, and infectious disease specialists who treat patients with HCV infection need a keen understanding of the stringent dosing and administration requirements of DAA agents to ensure optimal efficacy.
Read review of the app here
So Why Aren’t People Routinely Tested?
“Part of the issue is that doctors have other conditions to worry about, such as hypertension, diabetes and heart disease, but the other problem is that there’s no diagnosis code to support a routine test.”If they have abnormal liver enzymes, then they can check, but if they have normal liver tests — perfectly healthy — they don’t have an (internal classification of diseases) code,” Dr. Thuluvath said.
ICD codes are codes insurance companies use to determine payment, so if a test is run for a disease without a reason, the company may deny payment. Thuluvath said what’s needed is education for doctors and insurance companies.