Aethlon Medical's Hemopurifier moves forward at Medicity...

SAN DIEGO, Aug. 26 /PRNewswire-FirstCall/ -- Aethlon Medical, Inc. (OTC Bulletin Board: AEMD), the pioneer in developing therapeutic filtration devices to address infectious disease and cancer, announced today that the Medanta Independent Ethics Committee (MIEC) at Medanta, The Medicity Institute (Medicity) has approved a treatment program entitled: "Use of the Aethlon Hemopurifier® in Treating Chronic HCV Infection in Combination with Standard of Care (SOC) Drug Therapy."  The Medicity is a $360 million multi-specialty medical institute recently established on a 43-acre campus to be a premier center of medical tourism in India. The Aethlon Hemopurifier® is the first medical device to selectively target the removal of infectious viruses and immunosuppressive proteins from the entire circulatory system.  A clinical goal of the Aethlon-Medicity study will be to demonstrate that the Hemopurifier® is able to accelerate the benefit of HCV standard of care (SOC) drug regimens. Therapeutic filtration at the outset of SOC improves early virus reduction kinetics to levels associated with that of patients most likely to achieve a sustained viral response, which is the goal of HCV therapy. Additionally, lower quantities of HCV in circulation at the outset of SOC correlate with increased cure rates.

"We are grateful for this opportunity to show the pharmaceutical industry, infected patients, and shareholders that our Hemopurifier® can enhance the capabilities of drug regimens without adding additional drug toxicity and interaction risks", stated Aethlon Chairman and CEO, Jim Joyce. "Beneficial outcomes will set the stage for the early commercialization of our technology and should recalibrate industry viewpoints on addressing infectious disease conditions."

Upon the demonstration of early treatment benefit, Aethlon plans to advance commercialization through the Medicity and other regional treatment centers in India. In this regard, the company has entered into an agreement with GVK Biosciences (GVK BIO) to expand the opportunity for Aethlon to commercialize its Hemopurifier® treatment technology at three to five new clinical centers in India. GVK BIO is Asia's leading Discovery Research and Development organization. The HCV treatment opportunity for Aethlon is significant as greater than 20 million of the estimated 180 million people infected with HCV worldwide reside in India.  Based on patient feedback, Aethlon also believes that citizens of other nations may chose to travel to India to seek treatments that could resolve their HCV infection.

Aethlon further disclosed that the principal investigator of the clinical program, which has been registered with the Clinical Trials Registry of India, will be Vijay Kher, M.D., Chairman of the Department of Nephrology at the Medanta Kidney & Urology Institute. Dr. Kher previously served as the principal investigator of Hemopurifier® human studies to treat HCV at the Apollo and Fortis Hospital in Delhi, India. These studies demonstrated safety and effectiveness of the Hemopurifier® to reduce viral load in the absence of drug therapy. Patients enrolled in the Medicity study will receive a maximum of six Hemopurifier® treatments within the first week of initiating SOC drug therapy. In addition to monitoring for improved acceleration of viral load reduction at the outset of SOC, another primary endpoint will focus on rapid viralogic response (RVR) which is defined as undetectable viral load 30 days after SOC initiation. On average, approximately 15% of patients who initiate SOC therapy achieve a RVR.  Yet, those able to achieve a RVR have a greater than 88% likelihood of achieving a sustained viralogic response. The initiation of patient enrollment for the Medicity is conditional upon maintaining the treatment protocols approved by the MIEC and that clinical endpoint / efficacy assessment be further clarified by the principal investigator. Aethlon has also agreed to give consideration to compensating enrolled patients for lost wages while receiving Hemopurifier® treatment and other consideration should a material adverse event occur as a result of Hemopurifier® therapy.

ZymoGenetics completes enrollment in Phase 2b clinical trial for PEG-Interferon lambda...

SEATTLE--(BUSINESS WIRE)--Aug 25, 2010 - ZymoGenetics, Inc. (NASDAQ:ZGEN) today announced enrollment has been completed in the Phase 2b clinical trial with PEG-Interferon lambda and ribavirin in chronic hepatitis C virus (HCV) infection. ZymoGenetics is investigating PEG-Interferon lambda in collaboration with Bristol-Myers Squibb Company (NYSE:BMY) for the treatment of HCV infection. “We're very pleased to have completed the enrollment in the Phase 2b PEG-IFN lambda clinical trial in less than three months,” said Eleanor L. Ramos, M.D., Senior Vice President and Chief Medical Officer of ZymoGenetics. “The rapid enrollment to this study speaks to the motivation and enthusiasm of the clinical trial investigators to help address the unmet medical need in hepatitis C and also to the outstanding execution by our clinical team. We should now be able to assess the primary endpoint earlier than originally projected, and we look forward to assessing the data and planning for Phase 3.” The Phase 2 EMERGE study is an international, randomized multi-center clinical trial with PEG-Interferon lambda and ribavirin in treatment-naïve patients with HCV. The Phase 2b study enrolled 570 patients with genotypes 1, 2, 3 and 4 chronic HCV infection. The study is assessing the safety and antiviral efficacy of three doses of PEG-Interferon lambda (120 mcg, 180 mcg and 240 mcg) compared to PEGASYS®. Weekly subcutaneous doses of PEG-Interferon lambda or PEGASYS are being administered for 48 weeks in genotype 1 and 4 patients and for 24 weeks in genotype 2 and 3 patients. All patients also receive daily ribavirin. The primary endpoint of the trial is the proportion of patients who achieve undetectable levels of HCV RNA after 12 weeks of therapy (complete Early Virological Response). Achievement of Early Virologic Response will also be assessed by patient IL-28B genotype, which has been shown to be a robust predictor of treatment success with the combination of interferon-alpha and ribavirin. PEG-Interferon lambda PEG-Interferon lambda (IL-29) is a novel interferon in development for hepatitis C. The native human interferon lambda proteins are generated by the immune system in response to viral infection, and signal through a different receptor than type I interferons, such as interferon alpha. Because this receptor is present on fewer cell types within the human body, it is hypothesized that PEG-Interferon lambda may be able to demonstrate an improved safety and tolerability profile compared to alpha interferons.

Pharmasset starts Phase 2b clinical trial of polymerase inhibitor PSI-7977

PR Newswire US - Aug. 24, 2010

PRINCETON, N.J., Aug 24 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that dosing has begun in a Phase 2b study of PSI-7977, a nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C (HCV). The trial will evaluate PSI-7977 200mg QD and 400mg QD in combination with pegylated interferon alfa 2a and ribavirin, the current standard of care (SOC) in patients with HCV genotype 1 who have not been treated previously.

"We look for the Phase 2b to further support the efficacy, safety and resistance profile of PSI-7977 over 12 weeks, and to confirm a dose for continued development," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "Given the potent antiviral activity observed in the Phase 2a study and in vitro evidence for pan-genotype activity, we have also decided to include an exploratory, open label arm of patients with HCV genotype 2 and 3 who will receive a 12 week treatment regimen of PSI-7977 in combination with pegylated interferon and ribavirin. If successful, this shorter treatment regimen would be a first step toward defining a new treatment option for these patients."

About the Phase 2b Trial

The Phase 2b trial is anticipated to enroll approximately 125 patients infected with HCV genotype 1 who have not been treated previously. The primary endpoint of the trial will be the assessment of safety and tolerability of PSI-7977, in combination with SOC over 12 weeks with response-guided therapy allowing discontinuation of SOC at week 24. The trial will be conducted in the U.S. Patients will be randomized (2:2:1) into one of 3 arms:

• PSI-7977 200mg QD in combination with SOC for 12 weeks, followed by 12 or 36 weeks of SOC;
• PSI-7977 400mg QD in combination with SOC for 12 weeks, followed by 12 or 36 weeks of SOC;
• A control arm of matching placebo with SOC for 48 weeks.

Patients receiving PSI-7977 will discontinue treatment at week 24 if they achieve an extended RVR (eRVR), defined as HCV RNA below the limit of detection (<15 IU/ml) at week 4 and maintained until week 12. Patients who do not achieve an eRVR and all patients on placebo/SOC will continue on standard of care until week 48. Patients will be stratified by IL28B status to ensure balance across cohorts.

In addition, approximately 25 treatment-naive patients with HCV genotype 2 or 3 will be enrolled in a fourth, open label arm, receiving PSI-7977 400mg QD with SOC for 12 weeks, with no SOC follow-up. Patients will be followed for an additional 24 weeks after discontinuation of all therapy to assess SVR.

Pharmasset anticipates reporting interim data from this trial in the first half of 2011.

Achillion to Raise $50M in Stock Offering for HCV Studies

BioWorld Today - Aug. 20, 2010

Financings Roundup

Achillion Pharmaceuticals Inc. plans to raise about $50 million through the sale of stock and warrants to a select group of investors, money that would be used to advance the company's early stage pipeline of drug candidates for hepatitis C virus (HCV).

At the end of June, the New Haven, Conn.-based company had $20 million in cash resources. With the added funds from the financing, which is expected to close Aug. 20, Achillion hopes to extend its cash through most of 2012.

The financing is intended to take the company's ACH-1625 protease inhibitor to the completion of Phase IIa testing, explained Mary Kay Fenton, Achillion's vice president and chief financial officer.

The Phase II study, which is expected to get under way next month, will have a 28-day segment that is targeted to report data in March 2011 and a 12-week segment that is slated to report results at the end of next year.

"We believe this financing will get us through both of those milestones," Fenton told BioWorld Today.

In addition, Achillion hopes to move its preclinical candidates, ACH-2684, a pan-genotypic protease inhibitor, and ACH 2928, an NS5A inhibitor, through Phase I testing in 2011 . The company also plans to put those candidates in combination studies in 2012 with other HCV assets in development, Fenton said.

ACH-1625, while it has shown promising data in Phase Ib studies, is far behind the front runners in the crowded HCV space. Both Vertex Pharmaceuticals Inc. and Merck & Co. Inc. have their own HCV candidates in Phase III, protease inhibitors telaprevir and boceprevir, respectively. Analysts view both drugs as approvable.

The current standard therapy for HCV is a combination of ribavirin and a pegylated interferon. There are no protease inhibitors currently approved for the infection.

Achillion believes its protease inhibitor, though still in early testing, may stand apart from the others because of its safety and tolerability and sustained viral suppression.

"Based on the early Phase Ib data, we view ACH-1625 as a very promising HCV protease inhibitor in early development," Cowen & Co. analyst Phil Nadeau stated in a research note. He added, "We believe the risk/reward of owning ACHN shares at current levels is highly favorable."

In several dosing cohorts, study patients infected with HCV were dosed for five days and showed a mean maximum drop in viral load of between 3.63 and 4.25 logs. All dosing cohorts also showed a sustained viral suppression in HCV-infected subjects, even after dosing was completed.

"This observation could be an important distinguishing feature and competitive advantage for our compound in comparison to other HCV therapies," Elizabeth Olek, vice president and chief medical officer, said in a Thursday conference call.

A select group of investors, namely venture firms Domain Associates, Clarus ventures, Quaker BioVentures and Pappas Ventures, have agreed to purchase Achillion's stock and warrants in the private placement offering.

While the company's focus is HCV, it also has an HIV candidate elvucitabine, an L-cytosine nucleoside analogue reverse transcriptase inhibitor. Earlier this year, Achillion reported 96-week data showing that the drug had a substantial antiviral effect similar to 3TC (lamivudine, GlaxoSmithKline plc), with 95 percent of patients in the elvucitabine-treated group achieving undetectable viral load compared with 93 percent in the 3TC group.

Achillion is offering 19,755, 101 shares of common stock at a price of $2.49 per share, its consolidated closing bid price reported by NASDAQ Aug. 17.

The warrants to purchase 0.35 shares of common stock for each share of common stock are priced at $0. 125 per warrant share. The warrants, which have a seven-year term from the date of issuance, represent the right to acquire an aggregate of 6,921 ,285 shares of common stock and will be exercisable at a price of $3. 1125 per share.

Shares in Achillion (NASDAQ:ACHN) lost 1 cent, closing at $2.60 Thursday.

Aethlon Medical, Inc announces Hemopurifier® expansion into Hepatitis C...

Aethlon Medical Announces Expansion of Hepatitis C Virus (HCV) Treatment Programs

PR Newswire US - Aug. 18, 2010

SAN DIEGO, Aug. 18 /PRNewswire-FirstCall/ -- Aethlon Medical, Inc. (OTC Bulletin Board: AEMD), the pioneer in developing therapeutic filtration devices to address infectious disease and cancer, today announced that it has entered into an agreement with GVK Biosciences (GVK BIO) to expand the opportunity for Aethlon to commercialize its Hemopurifier® treatment technology at three to five new clinical centers in India.  The therapeutic focus at each center will be the implementation of the Hemopurifier® as an adjunct therapy to accelerate the benefit of HCV standard of care (SOC) drug regimens. Therapeutic filtration at the outset of SOC improves early virus reduction kinetics to levels associated with patients most likely to achieve a sustained viral response, which is the goal of HCV therapy.  GVK BIO is Asia's leading Discovery Research and Development organization.

Aethlon further disclosed that the Ethics Review Board (ERB) at Medanta, The Medicity Institute (Medicity) met on August 14th, 2010 to discuss the potential approval for Aethlon to initiate HCV treatment programs at the Medicity. Aethlon has been advised that a formal response should be expected from the Medicity ERB in the coming weeks. The Medicity is a $360 million facility recently established on a 43-acre campus to be a premier center of medical tourism in India.

About GVK Biosciences

GVK Biosciences (GVK BIO) is Asia's leading Discovery Research and Development organization. GVK BIO provides a broad spectrum of services, stand-alone and integrated, across the R&D value chain. GVK BIO's diverse portfolio of more than 100 customers includes Big Pharma, Agri & Life-sciences companies, leading biotechs and academic institutions. Spread across five locations in India and headquartered in Hyderabad, GVK BIO assists clients accelerate their research.  Additional information can be accessed at www.gvkbio.com.

About Aethlon Medical

At Aethlon Medical, we create revolutionary devices to address infectious disease and cancer. Our devices are designed to be novel platform solutions that fill therapeutic voids or aid in disease diagnosis and monitoring.

Our Hemopurifier® is the first medical device to selectively target the removal of infectious viruses and immunosuppressive proteins from the entire circulatory system. We recently discovered that our Hemopurifier® captures tumor-secreted exosomes that suppress the immune system of those afflicted with cancer. Prior to this discovery, a therapeutic strategy to directly inhibit or reverse the immunosuppressive destruction caused by exosomes did not exist in cancer care. By eliminating this mechanism, we believe our Hemopurifier® can fill an unmet clinical need and provide the benefit of an immune-based therapy without adding drug toxicity or interaction risks to established and emerging treatment strategies.

Human studies have documented the ability of our Hemopurifier® to safely reduce viral load in both Hepatitis-C virus (HCV) and Human Immunodeficiency Virus (HIV) infected patients without the administration of antiviral drugs.  However, our initial clinical and commercialization focus is to establish our Hemopurifier® as an adjunct therapy to enhance the benefit of both infectious disease and cancer treatment regimens. In this regard, we plan to commercialize our Hemopurifier® in India as we advance our clinical strategies in the United States and the European Union.  In vitro studies conducted by government and non-government research institutes have also verified that our Hemopurifier® has broad-spectrum capabilities against bioterror and emerging pandemic threats. These studies have confirmed the capture of Dengue Hemorrhagic Virus, Ebola Hemorrhagic Virus, Lassa Hemorrhagic Virus, West Nile Virus, H5N1 Avian Influenza Virus, 2009 H1N1 Influenza Virus, the reconstructed Spanish Flu of 1918 Virus, and Monkeypox Virus, which serves as a model for human Smallpox infection.

As a therapeutic device, the Hemopurifier® provides us with a pipeline into four significant market opportunities:

1. Cancer: A treatment candidate to improve patient responsiveness to established cancer therapies by removing immunosuppressive exosomes from circulation.
2. Hepatitis-C Virus (HCV): As an adjunct therapy to accelerate viral load reduction at the outset of standard of care drug regimens.  
3. Human Immunodeficiency Virus (HIV):  Provides a potential therapeutic option for HIV-infected individuals to manage disease progression once they become resistant to antiviral drug regimens.
4. Bioterror and Pandemic Threats:  Represents the most advanced broad-spectrum strategy to address untreatable bioterror and emerging pandemic threats.

The Hemopurifier® is an expansive multi-patented platform technology whose mechanism of action can be leveraged to provide therapeutic, diagnostic, and biomarker discovery solutions. As a therapeutic, the Hemopurifier® is a single-use disposable cartridge designed for implementation within the established infrastructure of dialysis machines and other blood circulatory pumps already located in hospitals and clinics worldwide.

In design, our Hemopurifier® is a selective filtration device containing affinity agents that tightly bind to high-mannose structures unique to the surface of exosomes produced by cancer and glycoproteins residing on the envelope of viruses. These agents are immobilized around approximately 2800 porous hollow fibers that run the interior length of our device. The resulting design provides us the novel ability to separate both exosome and viral targets away from blood cells so they can then be selectively and permanently removed from the circulatory system. In application, blood circulation is established into the Hemopurifier® via a catheter or other blood access device. Once blood flow has been established, treatment benefit is immediate as the entire circulatory system can pass through the Hemopurifier® in as little as 15 minutes.

Our wholly owned subsidiary, Exosome Sciences, Inc. (ESI) is focused on the development of exosome-targeted products and services that improve cancer diagnosis, provide post-treatment cancer surveillance, and aid in the discovery of biomarkers that allow doctors to optimize patient therapy. Additional information regarding Aethlon Medical and Exosome Sciences can be accessed online at www.aethlonmedical.com.

BioWorld Insight article "Telaprevir Looks Ever-Better, But Don't Discount Boceprevir"

BioWorld Insight - Aug. 16, 2010

HCV Wars

When Vertex Pharmaceuticals Inc. reported its first Phase III data for hepatitis C virus (HCV) protease inhibitor telaprevir in May, analysts predicted the 75 percent cure rate would be pretty hard to beat.

They were right. Earlier this month, Merck & Co. Inc.'s competing HCV protease inhibitor boceprevir reported a 66 percent cure rate in two Phase III trials. Piper Jaffray analyst Edward Tenthoff wrote that the lower cure rate was the "nail in the coffin" for boceprevir.

Other analysts echoed that sentiment last week, when Vertex reported a 72 percent cure rate in its second Phase III telaprevir trial. Wedbush PacGrow analyst Katherine Xu predicted that boceprevir will be able to capture just 40 percent of the market for treatment-naive HCV patients and 10 percent of the market for treatment-experienced patients. (See BioWorld Today, Aug. 11 , 2010.)

But don't count boceprevir out of the race just yet.

"Certainly not all of the data from either company has been reported yet," said Merck director of communications Bob Consalvo, referencing the fact that details will be presented this fall at the 2010 annual meeting of the American Association for the Study of Liver Diseases (AASLD).

Additionally, Merck reported boceprevir data from one treatment-naive trial and one treatment-experienced trial, while Vertex thus far has reported telaprevir data from two treatment-naive trials. The data from Vertex's pivotal Phase III treatment-experienced trial are expected next month.

Xu predicted that, on the whole, Vertex's treatment-experienced REALIZE trial might not have an overall cure rate as high as Merck's treatment-experienced RESPOND-2 trial. She noted that Vertex's trial includes null-responders who are hard to treat patients who did not respond to the standard of care while Merck's trial does not. "We believe stratification according to prior response is needed for a fair comparison" between the trials, she wrote in a research note.

Consalvo noted that claiming one population of HCV patients is harder to treat than another is "dicey," and can be impacted by when initial response is tested and what assays are used. He predicted that determining the best ways to measure a patient's responsiveness will become a key topic for clinicians to discuss moving forward.

Another topic expected to command plenty of focus at AASLD is response-guided therapy. Both Vertex and Merck have been using early viral load measurements to determine whether patients would need a full 48-week course of treatment, or if they could stop early and still get a cure. Given the nasty side effects associated with HCV drugs, a shorter duration of treatment would be a boon for doctors and patients.

Vertex tested response-guided therapy in its two treatment-naive trials, but not in its treatment-experienced REALIZE trial. Consalvo noted that Merck's treatment-experienced RESPOND-2 trial did test response-guided therapy and found that early responders who stopped treatment after 36 weeks rather than continuing for 48 weeks still achieved a 59 percent cure rate. Compared to a 21 percent cure rate for the group who did not get boceprevir, that's "a really good result," Consalvo said.

He added that the "opportunity for patients to have a high [cure rate] and stop treatment early . . . is significant."

But even if Vertex's cure rates in REALIZE trounce Merck's in RESPOND-2, there's another reason that both drugs may find a place in the market: resistance. Many of the patients in both companies' treatment-experienced trials are "relapsers" who had a strong initial response to the standard of care but eventually developed resistance. It's an issue that plagues all anti-infectives and requires a steady stream of new drugs.

In fact, Consalvo cited resistance as the reason Merck decided to exclude null-responders from its RESPOND-2 trial. Although both boceprevir and telaprevir are given on top of the standard of care, patients who don't respond to that standard would essentially be receiving just the protease inhibitor, which Merck felt could contribute to resistance.

That's something that will have to be hashed out in the real world as well, Consalvo said. Is treating null-responders, who will likely have a low chance of responding to the protease inhibitors as well, worth the risk of resistance? Such questions will need to be answered on a case-by-case basis, Consalvo said.

Keeping score on the STAT-C / DAA agents??

Here's a very nice resource if you're keeping tabs on the development of the new agents for the treatment of Hepatitis C - HCVdrugs.com .  Includes links to Clinical Trials.org that offers details about the trial design and locations.

PSI-7977 Receives Fast Track Designation from the FDA for the Treatment of Chronic Hepatitis C Infection

PRINCETON, N.J., Aug. 12 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) has received fast track designation from the U.S. Food and Drug Administration (FDA) for PSI-7977 for the treatment of chronic hepatitis C virus (HCV) infection. PSI-7977 is an oral uridine nucleotide analog polymerase inhibitor of HCV. Pharmasset recently completed dosing in a 28 day Phase 2a trial to evaluate PSI-7977 in combination with Pegasys (pegylated interferon) plus Copegus (ribavirin) in treatment-naive patients chronically infected with HCV genotype 1. Pharmasset expects to initiate a 12-week Phase 2b study of PSI-7977 in the fourth quarter of 2010.

Under the FDA Modernization Act of 1997, fast track designation may facilitate the development and expedite the review of a drug candidate that is intended for the treatment of a serious and life-threatening condition and demonstrates the potential to address an unmet medical need for such a condition. PSI-7977 was granted the fast track designation primarily due to the need for HCV treatments with novel mechanisms of action, oral administration, different resistance profiles and improved safety and efficacy over the existing standard of care for both treatment-naive and treatment-experienced patients.

"The FDA's fast track designation for PSI-7977 acknowledges the urgent need for new HCV drugs," stated Dr. Michael Rogers, Pharmasset's Chief Development Officer. "Currently, there are no HCV nucleoside/tide inhibitors approved for the treatment of chronic HCV infection. We continue to work closely with the FDA on the development and regulatory review of PSI-7977, which has demonstrated compelling antiviral activity, a high barrier to resistance and has been generally well-tolerated in clinical trials to date."

Vertex releases data on it's ILLUMINATE study supporting 24-week Telaprevir therapy in Genotype 1 Treatment Naive subjects.

-Viral cure rates of 92% and 88% with 24 and 48-week regimens, respectively, in people who met certain response criteria-

-Safety and tolerability results were similar to those seen in the Phase 3 ADVANCE study-

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Aug 10, 2010 - Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced results from the Phase 3 ILLUMINATE study, which was designed to evaluate whether there was any benefit to extending therapy from 24 to 48 weeks in people whose hepatitis C virus (HCV) was undetectable at weeks 4 and 12 of treatment (extended rapid viral response or eRVR). People in the trial who met these eRVR criteria and who remained on treatment were then randomized at week 20 to receive 24 or 48 weeks of total treatment. People who did not meet these criteria were assigned to 48 weeks of pegylated-interferon and ribavirin therapy.

Sustained viral response (SVR or viral cure) rates of 92% and 88% were observed in the randomized 24 and 48-week telaprevir-based treatment groups, respectively. 72% of all 540 people treated with telaprevir in the study achieved a viral cure. The safety and tolerability profile of the telaprevir-based regimen was consistent with results reported previously from the pivotal Phase 3 ADVANCE study.

“The viral cure rates seen in ILLUMINATE showed that there was no benefit to extending telaprevir-based therapy to 48 weeks for the majority of people,” said Kenneth Sherman, M.D., Ph.D., Professor of Medicine at the University of Cincinnati College of Medicine, Director of the Division of Digestive Diseases for UC Health and Principal Investigator of the trial. “Patients who had a rapid response to telaprevir-based regimens at weeks 4 and 12 had a high likelihood of achieving a cure with 24 weeks of total treatment, which may provide important information to motivate people to continue therapy.”

“Data from ILLUMINATE and ADVANCE support our belief that the use of 24-week telaprevir-based therapy within a response-guided regimen may provide an important future treatment option for people with hepatitis C,” said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex.

Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being developed by Vertex Pharmaceuticals in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. Results from the ILLUMINATE study are expected to supplement data obtained from ADVANCE and REALIZE - the two pivotal Phase 3 studies of telaprevir - as part of a New Drug Application submission to the U.S. Food and Drug Administration planned for the fourth quarter of 2010.

Efficacy Results from ILLUMINATE

Primary analysis for people who met certain response criteria*:

24-week telaprevir-based treatment regimen:

• SVR Rate: 92% (149/162)
• Relapse Rate: 5.7% (9/159)

48-week telaprevir-based treatment regimen:

• SVR Rate: 88% (140/160)
• Relapse Rate: 1.9% (3/154)

*Reflects people whose hepatitis C virus was undetectable (<25 IU/mL and undetectable by Roche COBAS Taqman HCV test) at weeks 4 and 12 (eRVR) and who remained on treatment through week 20.

Overall efficacy analysis for all patients treated with telaprevir in ILLUMINATE (ITT or intent-to-treat analysis):

• SVR Rate: 72% (388/540)
• Relapse Rate: 7.7% (36/469)
• Rapid Viral Response (RVR) Rate: 72% (389/540)
• Extended RVR (eRVR): 65% (352/540)

Safety & Tolerability Results from ILLUMINATE

The safety and tolerability profile of the telaprevir-based regimen in the ILLUMINATE study was similar to results reported from the Phase 3 ADVANCE study. The most common adverse events reported in the ILLUMINATE study, in order of frequency, were fatigue, pruritus, nausea, anemia, rash and headache. The majority of these adverse events were mild or moderate. Adverse events leading to discontinuation of all study drugs during the 12-week telaprevir dosing period occurred in 6.9% of people in the study. Treatment discontinuation of all drugs due to anemia and rash occurred in 1.1% and 0.6% of people in the study, respectively, during the telaprevir dosing period. Like in ADVANCE, the use of erythropoiesis-stimulating agents (ESAs) was not allowed in this study.

Data from ILLUMINATE have been submitted for presentation at the 2010 Annual Meeting of the American Association for the Study of Liver Diseases.

About the ILLUMINATE Trial

ILLUMINATE was a Phase 3, supplemental, open-label, randomized study in people infected with genotype 1 chronic hepatitis C, the most common form of the virus in the U.S. and Europe, who had not been previously treated (treatment-naïve). In this study, people who met protocol-defined response criteria of achieving eRVR were randomized at week 20 to receive 24 or 48 weeks of total treatment. The primary endpoint of the study was the proportion of patients who achieved SVR in the randomized treatment groups, and evaluated by a non-inferiority analysis. Based on this analysis, the study achieved its primary endpoint of non-inferiority with respect to SVR rates in the randomized 24 and 48-week telaprevir-based arms. The trial enrolled people at 76 clinical trial sites in the U.S. and Europe. A greater proportion of people in the ILLUMINATE study (approximately 90%) were enrolled at U.S. sites compared to the proportion in ADVANCE. As in all studies evaluating telaprevir-based regimens, patients received no more than 12 weeks of triple therapy (telaprevir, pegylated-interferon and ribavirin) followed by pegylated-interferon and ribavirin only, as part of either 24 or 48 weeks of total treatment, as noted in the trial design.

About the Telaprevir Development Program

To date, more than 2,500 people with hepatitis C have received telaprevir-based therapy as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE trials. Together, these studies enrolled people with genotype 1 hepatitis C who had not been treated for their disease previously as well as people who had been treated before but did not achieve a viral cure. The telaprevir clinical development program is the largest conducted to date for any investigational direct-acting antiviral hepatitis C therapy.

Phase 3 ADVANCE Trial

The pivotal Phase 3 ADVANCE study evaluated telaprevir-based response-guided regimens in 1,095 treatment-naïve patients. Data from this trial has been accepted for presentation at the 2010 Annual Meeting of the American Association for the Study of Liver Diseases.

Phase 3 REALIZE Trial

The second pivotal Phase 3 study, REALIZE, which is being conducted by Vertex's collaborator Tibotec, is evaluating telaprevir-based regimens in approximately 650 people who did not achieve a viral cure with a prior pegylated-interferon based treatment. REALIZE is the only current Phase 3 study of an investigational hepatitis C therapy to enroll a difficult-to-treat population that includes patients who had a null response and failed to achieve a viral cure with a prior course of hepatitis C therapy. Topline data from REALIZE are expected in September 2010.

Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.

The Lancet publishes final SPRINT-1 data from Merck's Boceprevir...

INDIANAPOLIS — Adding a direct acting anti-viral drug to the standard treatment regimen for hepatitis C significantly increases the cure rate in the most difficult to treat patients, according to a research report published Monday in the online edition of the journal The Lancet.

The research team, led by Paul Kwo, M.D., of Indiana University School of Medicine, reported that adding the drug nearly doubled the treatment's effectiveness when given for 48 weeks in one treatment arm of the study.

An estimated 3.2 million Americans and 170 million people worldwide are infected with the hepatitis C virus, but many do not know it. In the United States, 70 percent of affected individuals are infected with genotype 1 hepatitis C, the most difficult to treat. Although there may be no symptoms for years, long-term infection can cause cirrhosis and the disease is a leading cause of liver cancer and liver transplantation. Hepatitis C infections occur mainly through transmission of infected blood, such as via injection drug use, and there is no vaccine.

Currently fewer than half of patients with genotype 1 hepatitis C are treated effectively by the standard combination of two drugs, peginterferon alfa-2b plus ribavirin, which is typically given for 48 weeks. The treatment can be difficult for some patients due to anemia and other side effects.

Adding the drug boceprevir increased the cure rate to as high as 75 percent in those who received 48 weeks of the three-drug combination therapy, compared to 38 percent of those in the control group, who received the standard two-drug treatment for 48 weeks, said Dr. Kwo, associate professor of medicine at the IU School of Medicine. The two-year phase 2 trial was conducted at 67 sites with 520 patients in the U.S., Canada and Europe.

In the boceprevir study, known as the SPRINT-1 trial, researchers tested several different options to evaluate the effectiveness of the combination therapy:

To test whether the addition of boceprevir could make it possible to shorten treatment times, some patients were randomly selected to receive the three-drug combination for 28 weeks, some for 48 weeks.
Researchers also investigated whether a 4 week lead-in with the standard two-drug combination prior to the addition of boceprevir to the treatment regime could improve sustained virologic response rates. The goal was to see if allowing the interferon and ribavirin to reach steady state levels -- which would activate the immune system and reduce virus levels -- before adding boceprevir would improve the response rates as well as reduce the virus' ability to develop resistance to boceprevir, said Kwo.

In another arm of the trial, researchers tested whether a lower dose of ribavirin could reduce the anemia side effects while still treating the virus effectively.

"Both 28- and 48-week boceprevir regimens significantly increased sustained virologic response rates – which is the best definition of a cure we have – compared to the 48 week control," said Dr. Kwo. "The 48-week treatment arm with 4 weeks of peg interferon lead-in and 44 weeks of peg interferon, ribavirin, and boceprevir led to the largest improvement over the control group ever reported. That's very impressive."

Boceprevir, a product of Merck & Co., is an HCV protease inhibitor – a compound designed to block a function key to viral reproduction in the cell. Boceprevir directly targets the hepatitis C virus, Kwo noted, while peginterferon and ribavirin are less specific, acting more generally to stimulate the body's virus-fighting immune system.

The best results were reported for the 103 patients who were treated for four weeks with the standard two drug regiment, followed by 44 weeks of the three-drug regimen including boceprevir: 75 percent of these patients tested negative for evidence of the virus six months after the end of treatment. Results for the other treatment arms were:

67 percent of those who received the three drug regimen for 48 weeks with no lead-in treatment tested negative for the virus (103 patients).

56 percent of those who received the two-drug lead-in for four weeks, followed by 24 weeks of the three drug treatment tested negative for the virus (103 patients).

54 percent of those who received the three-drug treatment for 28 weeks with no lead-in tested negative for the virus (107 patients).

38 percent of the control group, who received the standard two-drug treatment for 48 weeks tested negative for the virus (104 patients).

Patients receiving the low-dose of ribavirin did not fare as well – just 36 percent were virus-free after 48 weeks of treatment.

"Based on this phase 2 study, it appears that if this drug receives final approval approximately two-thirds of patients will be able to be treated successfully with 28 weeks of treatment and one-third will need 48 weeks of treatment, though this will require confirmation from the phase 3 trials, from which preliminary results were recently released," said Dr. Kwo.

The Street.com picks a winner in the battle of the STAT-C agents....

WHITEHOUSE STATION, NJ (TheStreet) -- Vertex Pharmaceuticals(VRTX) defeats Merck(MRK) in the first battle of the hepatitis C drug war.

Merck said Wednesday that between 63% and 66% of hepatitis C patients never treated before achieved a viral cure after receiving the company's experimental drug boceprevir plus the standard of care, according to top-line results from a phase III study known as SPRINT-2.

These boceprevir cure rates were significantly higher than the 38% of hepatitis C patients cured using standard of care alone. On these data, Merck said it will seek approval of boceprevir in the U.S. and Europe by the end of the year.

If approved, boceprevir may have a tough time competing against Vertex's hepatitis C drug telaprevir, which will also be filed for approval later this year. Results from a similar Vertex study in so-called "treatment-naïve" hepatitis C patients released in May showed that telaprevir plus the standard of care achieved a cure rate of 75%.
 
Moreover, patients can be cured of the hepatitis C virus using Vertex's telaprevir in as little as 24 weeks, while the shortest treatment duration with Merck's boceprevir is 28 weeks.

It's important to note that boceprevir and telaprevir have never been matched head to head in a single study, but that doesn't stop analysts and investors from comparing the efficacy and safety of the two drugs.
"The [boceprevir] data look ok from an efficacy and safety standpoint but we believe that they are inferior to what telaprevir has demonstrated thus far," wrote ISI Group biotech analyst Mark Schoenebaum in an email to clients soon after Wednesday's announcement.

In early trading, Vertex shares were up 5% to $37.04. Merck was essentially flat at $34.85.
Merck Wednesday also released data from a second phase III study known as RESPOND-2 which tested boceprevir in patients who previously failed to respond to treatment with standard of care.
In this study, cure rates for boceprevir patients (who also received standard of care therapy) ranged from 59% to 66%. By comparison, patients who were re-treated with standard of care achieved cure rates of 21%.




Vertex is running a similar study of telaprevir in treatment-experience hepatitis C patients, with results expected in September.

Full data presentations for both telaprevir and boceprevir will be made at the American Association for the Liver Disease (AASLD) annual meeting in early November.

LabCorp Gains Rights to Merck & Co.'s IL-28B Polymorphism IP for HCV Therapy Predictive Test...

Merck & Co. has granted LabCorp a nonexclusive license to use the IL-28B polymorphism in a commercial test to help predict an HCV patient's response to peginterferon alpha-based therapy. Merck will receive an up-front fee from LabCorp plus royalties on sales of tests covered under the deal.
 
LabCorp has already developed an in vitro assay to identify the IL-28B polymporphism in HCV patients. An association between the polymorphism and peginterferon alpha response was identified by Merck and collaborating scientists through a genome-wide association study of nearly 1,700 HCV genotype-1 patients, the firm points out. The IL-28B link with HCV therapy identified through the Ideal study was first reported last year, and full data from the trial was published in Gastroenterology in May.
 
Merck says it plans to provide a limited number of nonexclusive licenses to the IL-28B polymorphism to established diagnostics companies. Global sales of the firm's peginterferon alfa-2b HCV therapy Pegintron were $186 million in the first quarter of 2010.