Original article: The REAL drug to beat in Hepatitis C treatment: Ribavirin

An article I authored and recently published online thanks to the great folks at GastroHep.tv, a multi-media, cutting edge online resource for the Gastroenterology and Hepatology community. 



The REAL Drug to Beat in Treating Hepatitis C: Ribavirin

by Chris Barnes

By now, most of us are aware – some of us painfully so – that the Hepatitis C drug development market is red hot. Investors and developers alike need a scorecard to keep track of who is buying who and for what potential blockbuster drug in the race to make it big in treating Hepatitis C.  All of this hullabaloo is for good reason – the CDC estimates there are over 170 million people infected with Hepatitis C worldwide[1], a vast majority of them don’t know that they have it.  That is paradoxically both an enormous and lucrative problem. This means there are a lot of potential patients for pharmaceutical companies to treat with blockbuster anti-HCV drugs.

The names of the compounds in development are like alphabet soup – GS-7977, VX-222, BMS-790052, BI-201335, TMC 435, BL-8020… protease inhibitors, polymerase inhibitors, cyclophilin inhibitors… the list goes on and on. This is a good thing for both drug makers and patients. Drugs to treat Hepatitis C are becoming more potent and more tolerable.  And the race for the next blockbuster drug means there is no shortage of drugs and drug classes to choose from.  Drug developers may even realize the holy grail of Hepatitis C treatment – an all oral, interferon-free regimen consisting of 2-4 pills a day. That’s right, no shots, no interferon. This would potentially make treatment for Hepatitis C infinitely more tolerable for patients.

So the HCV drug development biz is booming… but the hottest drug to beat in Hepatitis C?  Ribavirin.  A cheap, generic anti-viral. It turns out that even with all the advances drug makers are realizing in interferon-free drug combinations, ribavirin is critical to the success in curing patients of Hepatitis C.   The trouble is that no one is really sure how ribavirin works. All we know is that treatment response rates are infinitely higher when it is part of a Hepatitis C antiviral regimen.[2][3][4]

Researchers are busy trying to find out just what makes ribavirin tick, but let’s look at a few of the current theories on how the drug works:

Ribavirin may cause something called ‘error catastrophe’ in the lifecycle of the HCV virus.[5]Ribavirin is a nucleoside analog – this means that ribavirin can fool the virus into thinking that it’s one of the building blocks needed for the virus to replicate. So when the virus tries to replicate itself, it picks ribavirin as a building block instead of the real thing. This mucks up the replication process leading to ‘error catastrophe’ – in other words, the virus is no longer able to make copies of itself.
Inosine monophosphate dehydrogenase (IMPDH). That’s a tongue-twister to be sure, but it’s also a cellular enzyme the human body makes and the HCV virus needs. Ribavirin may inhibit this enzyme, which consequently shuts down the energy supply the Hepatitis C virus requires to survive and replicate.[1]
The Hepatitis C virus is sneaky. It has a peculiar knack for evading the body’s immune system[2], so anything that might disrupt that ability would be very valuable to an anti-HCV regimen. It turns out that ribavirin may have this unique ability by helping the body mount a specific anti-viral response to the Hepatitis C virus, which is essential in fully clearing the virus. [3]
While ribavirin’s exact mechanism of action remains a mystery, there is one thing we do know for certain – we need ribavirin to fight Hepatitis C. Paring ribavirin with the above new antiviral compounds currently in development – called Direct Acting Antivirals  or DAAs -  that target and disrupt numerous points in the lifecycle of the virus, lead to significantly better cure rates then just using the DAAs alone. While interferon may go the way of the buffalo, it appears that the lowly, unsexy ribavirin is here to stay.  This makes ribavirin the REAL drug to beat in the Hepatitis C drug development marketplace.

References

[1] Perz JF, et al. The contribution of hepatits B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006; 45: 529-38

[2] Vertex Pharmaceuticals, Inc. (2010)  Vertex adds ribavirin in additional treatment arm in ongoing phase II VX-222 & Telaprevir combo trial. [Press Release] Retrieved from http://viralmatters.blogspot.com/2010/11/vertex-adds-ribavirin-in-additional.html

[3] Hezode, Christopher, et al. (2009) Telaprevir and Peginterferon with or without Ribavirin for chronic HCV Infection. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMoa0807650

[4] Smith, M. (2012). New Combo KOs HCV Without Interferon, Ribavirin  [Online article] Retrieved from: http://www.medpagetoday.com/InfectiousDisease/Hepatitis/30739

[5] Maag D, et al. RNA virus error catastrophe: direct molecular test by using ribavirin. Proc. Natl. Acad. Sck. 2001; 98: 6895-900

Seeking Alpha: Addressing Vertex/Gilead Confusion...

Posted 3-1-2012 on Seeking Alpha.com: More on HCV drug development investment 'irrational exuberance', the author making a case that investors have given Vertex the bum's rush and should take another look. 

Addressing Vertex / Gilead Confusion
March 1, 2012
Contributor: Prohost Biotech

Hepatitis C virus (HCV) treatments are moving stocks of HCV developers up and down in a chaotic way that makes no sense. While Vertex’ (VRTX) Incivek sales have been breaking the record of drug sales, investors who have been fed immature and unconfirmed knowledge that Pharmasset’s oral HCV therapeutics combination will render Incivek obsolete caused a sell-off in VRTX. Investor logic that patients would definitely prefer all oral drugs over a combination that has injectable alfa interferon is undisputable, that’s we too are waiting for a successful all oral HCV treatment, which has yet to emerge.

With the media stressing that Pharmasset was the firm that will put the magic combination on the market, Pharmasset's stock doubled from over $20 in January 2010, to around $45 at the end of December. In 2011, the stock rallied again from $45 in January to $135 in August, split 2 to 1 and started climbing back from around $66 to $72. The firm was then acquired by Gilead (GILD), which paid an additional 67% premium over its obese market price, i.e., around over $130 per share.

This scenario does not make sense to us. Contrary to the market’s culture, investors, for one reason or another, sold a real present to buy a future designed on mere speculation. They sold VRTX, a company that had a marketed HCV drug, which is the first ever to represent a cure for the life-threatening HCV infection and whose sales have been actually generating record revenues to buy into Pharmasset’s oral combination while still in mid-trial and requires more lengthy experimentation before confirming the all-oral combination’s safety and long-term efficacy.

Just before concluding the acquisition deal, on December 16, 2011, Pharmasset surprisingly announced its decision to discontinue all treatment arms with a regimen containing its drug PSI-938 because of laboratory abnormalities associated with liver function in subjects receiving the drug at a dose of 300 mg/day. This news surprised investors, especially Gilead’s shareholders who began to question the value of the deal with Pharmasset. The news did not alter Gillead’s decision to acquire the company. After the acquisition, Gilead’s stock experienced a temporary retreat. Many investors believed that $11 billion was an unprecedented high amount of money to be paid for molecules that have yet to complete clinical trials, confirming their superiority as described by the media since 2009. Investors’ temporary negative reaction toward the deal was the only understandable action in this story.

It did not take time for GILD to fiercely rebound after the firm announced its financial results. The stock was up to $56, matching its new high for the past three years. Less than two months later, though, other trial results with Pharmasset’s combination on HCV genotype 1 patients with a prior “null” response to an interferon-containing regimen demonstrated that the majority of patients experienced viral relapse within four weeks of completing 12 weeks of treatment with what has become Gilead’s combination of GS-7977 plus ribavirin (RBV). GILD tumbled, trading now at around $45, after loosing around 15% of its value.

In the mean time, Vertex is generating millions of dollars selling its selective HCV protease inhibitor. Its stock, though, remained boxed - sold every time it makes an attempt to rally even though Vertex is also trying its own all-oral combination. The stock remained boxed even after 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 have demonstrated promising safety and efficacy and after learning that the 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 FDA for the first interferon-free regimen for genotype 1 (1a and 1b) patients by the end of 2014 or beginning of 2015.

Investors didn’t even bother considering the fact that Vertex and its collaborator Alios BioPharma are conducting Phase 1 studies of two structurally-distinct nucleotide polymerase inhibitors, ALS-2200 and ALS-2158. Vertex has begun the first seven-day viral kinetic studies of ALS-2200 and ALS-2158 in people with genotype 1 hepatitis C, whose safety and viral kinetic data expected in the second quarter of 2012. Positive results would 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.

What continued to make no sense at this stage is that investor pessimism with Gilead's all-oral combination that erased 15% of GILD price, did not transform into optimism for VRTX, which was cremated by the enthusiasm for Gilead’s drug that investors are now experiencing doubt about. It looks as if investors are sensitized to not appreciate the firm that introduced the first HCV cure and the first approved cystic fibrosis drug that works at the root cause of the disease, knowing in fact that Vertex has plans ready to bring breakthrough treatments to all cystic fibrosis patients.

Gilead is a great firm and at the end of the day it will probably succeed in bringing an HCV breakthrough treatment to the market. But this does not mean that Vertex will not succeed reaching the same goal. Vertex is also a great firm that has already changed the way chronic life-threatening diseases have been treated. Gilead has a lot of current and upcoming good news and so does Vertex. The HCV market is huge. It requires more than one, or two treatments to satisfy its needs.

Disclosure: We are long both firms.

Vertex Pharmaceuticals posts ZENITH all oral combo interim results...

Posted 2/23/12 on Fierce Biotech - Interim results from Vertex's ZENITH trial, looking at an all-oral combo of Telaprevir, non-nuc VX-222 and Ribavirin for 12 weeks. Eleven of 46 Tx-naive G1 patients met the week 2 and 8 criteria of having undectectable virus  and were eligible to stop all treatment at week 12.  Nine of the 11 achieved SVR4, with equal viral kinetics for both G1a and G1b.  VRTX is pushing this combo ahead into Phase IIb studies, with a hopeful eye on possible NDA filing in late 2014 .


Vertex vows to race ahead with interferon-free combo for hep C
February 23, 2012 — 10:50am ET | By John Carroll
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Determined to try and keep pace with rival next-gen hepatitis C treatments in the pipeline, Vertex ($VRTX) today unveiled a slate of somewhat positive interim midstage results for an all-oral combo regimen that includes its game-changing drug Incivek along with the experimental VX-222--its non-nucleoside polymerase inhibitor--and ribavirin.

The standard goal for new hepatitis C drugs is the sustained elimination of all signs of the virus by week 12, allowing patients to stop treatment, though developers are aiming for the fastest cure rates possible. Vertex noted that 11 of 46 treatment naïve patients with the genotype 1a and 1b virus 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 showed that viral loads were below the "lower limit of quantification" for 83% of the patients at week 12.

Based on the data, Vertex says it will push ahead with a Phase IIb study of the interferon-free combo, anticipating that investigators can nail late-stage data for an NDA to the FDA as early as late 2014--keeping on an ambitious development schedule.

"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," said Vertex CSO Peter Mueller. "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."

Those two nucleotide polymerase inhibitors he referred to are ALS-2200 and ALS-2158, which were licensed in from Alios and perhaps represent Vertex's best shot at gaining an edge over treatments being studied at rival companies. Vertex said 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, enabling the launch of midstage studies in the second half of 2012.

Incivek sales drive Vertex 3rd quarter profit...

$420 million in net product revenues for Incivek in the third quarter helped Vertex record a record net income or $221 million sending shares up almost 2% today, this despite a recent rumored stall in the sales trajectory for Incivek. The company also gives an update to it's HIV/HCV co-infection trial (an exceptionally under-served part of the population), potential BID dosing, a 12 week study of TVR + P/R in patients with the 'CC' variation near the IL28B gene and it's quad therapy trial looking at it's VX-222 polymerase inhibitor + P/R

CAMBRIDGE, Mass., Oct 27, 2011 (BUSINESS WIRE) -- ---Continued strength in launch of INCIVEK for hepatitis C; submissions of KALYDECO(TM) (VX-770, ivacaftor) approval applications complete-

Vertex Pharmaceuticals Incorporated /quotes/zigman/79675/quotes/nls/vrtx VRTX +1.81% today reported consolidated financial results for the quarter ended September 30, 2011 and provided an update on the launch of INCIVEK(TM)(telaprevir) tablets and its development programs evaluating potential new medicines.

The company reported total revenues of approximately $659 million, including approximately $420 million in net product revenues for INCIVEK in the third quarter. Vertex recorded net income of approximately $221 million, or $1.02 per diluted share, on a GAAP basis and approximately $151 million, or $0.70 per diluted share, on a non-GAAP basis for the quarter. Vertex ended the quarter with a cash position of approximately $659 million.

Vertex also today provided an update on ongoing and planned clinical trials for its broad pipeline of potential new treatments for hepatitis C, cystic fibrosis, rheumatoid arthritis, epilepsy and influenza. In addition to INCIVEK, Vertex has seven other potential medicines in clinical development.

"Our continued progress with the launch of INCIVEK together with our global approval applications for KALYDECO highlight Vertex's strengths in moving innovative science from the lab to people with serious diseases," said Matthew Emmens, Chairman, President and Chief Executive Officer of Vertex. "As we enter 2012, we expect to have more than a dozen ongoing clinical trials across our broad and diverse pipeline, which we believe may lead to additional new medicines to support our future growth."

"More than 17,000 people with hepatitis C have started treatment with INCIVEK since its approval in May, underscoring the strength of the launch," said Nancy Wysenski, RN, Executive Vice President and Chief Commercial Officer. "We are focused on further broadening the number of doctors using INCIVEK and are continuing to work with the hepatitis C community to increase awareness and screening and to help ensure patients are able to get the support they need."

Recent Progress and Upcoming Milestones

Hepatitis C

INCIVEK Now Available in Multiple Countries

-- In the third quarter, Vertex announced the availability of INCIVEK for people in Canada who have chronic genotype 1 hepatitis C. INCIVEK is the first medicine marketed in Canada by Vertex.

-- Vertex's collaborator, Janssen, announced in September that the European Commission approved telaprevir in Europe, where it is being marketed by Janssen as INCIVO(R). INCIVO is now available in the U.K., Germany, France and Sweden. Also in the third quarter, Vertex's collaborator Mitsubishi Tanabe Pharma announced the approval of telaprevir in Japan, where it will be marketed by Mitsubishi as TELAVIC(R).

Phase 3b Study of INCIVEK Dosed Twice Daily

-- Vertex is currently conducting a Phase 3b clinical trial to evaluate twice-daily dosing of INCIVEK (1,125 mg; BID) compared to three-times-daily dosing of INCIVEK (750 mg; q8h) in combination with Pegasys(R) (pegylated-interferon alfa-2a) and Copegus(R) (ribavirin) for people with chronic genotype 1 hepatitis C. Sustained viral response (SVR, or viral cure) data from OPTIMIZE are expected as early as the second half of 2012, which could support the submission of a supplemental New Drug Application (NDA) for twice-daily dosing of INCIVEK by the end of 2012.

Phase 3b CONCISE Study Underway Evaluating 12-week Regimens of INCIVEK Combination Treatment

-- Earlier this week, Vertex announced the start of a Phase 3b trial to evaluate the potential for treatment with INCIVEK(TM) combination therapy to be shortened to 12 weeks in people with genotype 1 chronic hepatitis C who have the 'CC' variation near the IL28B gene. Approximately one-third of people with hepatitis C have the 'CC' genotype, which has been associated with higher sustained viral response (SVR, or viral cure) rates and faster response to interferon-based treatment. The trial is expected to include approximately 350 people with genotype 1 chronic hepatitis C who have not previously been treated and people who have relapsed after at least one prior course of treatment with pegylated-interferon and ribavirin alone.

Enrollment Complete in All-Oral Arms of Phase 2 ZENITH Study of INCIVEK and VX-222

-- Vertex completed enrollment in the third quarter in the two, all-oral three-drug treatment arms of the ongoing Phase 2 ZENITH clinical trial evaluating response-guided regimens of Vertex's lead investigational hepatitis C virus polymerase inhibitor, VX-222, dosed in combination with INCIVEK and ribavirin. The all-oral, three-drug treatment arms are evaluating a twice-daily, interferon-free regimen of INCIVEK (1,125 mg), VX-222 (400 mg) and ribavirin in people with genotype 1a or 1b chronic hepatitis C. Vertex expects to obtain end-of-treatment data from the all-oral arms of the study in early 2012.

-- Two four-drug (quad) arms of the study are also fully enrolled and are evaluating response-guided four-drug combinations of VX-222 (400 mg or 100 mg; BID), INCIVEK (1,125 mg; BID), pegylated-interferon and ribavirin.

-- Earlier this year Vertex announced interim data from ZENITH and expects to provide additional data from the four-drug arms at the upcoming Liver Meeting in November.

Multiple INCIVEK and VX-222 Presentations at the Liver Meeting in November

-- At the 2011 Liver Meeting, being held in San Francisco, November 4-8, Vertex expects to present clinical data from multiple studies of INCIVEK and VX-222. New data, including sustained viral response (SVR, or viral cure) results from the ZENITH study, will be presented for the first time. Additionally, new data from a Phase 2 study evaluating INCIVEK combination treatment in people co-infected with genotype 1 chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV), will be presented at the meeting.

Phase 3b HCV-HIV Co-infection Trial to Begin This Year

-- Based on data from a Phase 2 trial of INCIVEK combination treatment in people co-infected with HCV and HIV, Vertex plans to initiate a Phase 3b trial of INCIVEK in people co-infected with HCV and HIV by the end of 2011. The trial is expected to enroll approximately 150 people and will be designed to provide safety and efficacy data to support registration of INCIVEK for the treatment of HCV-HIV co-infection as early as 2013. All patients in this trial will receive INCIVEK combination treatment. Vertex's collaborator Tibotec also plans to conduct a similar trial in Europe, which will provide additional safety and efficacy data in people co-infected with HCV and HIV. Tibotec expects to begin enrollment in this study in early 2012.

First Phase 2b Study of INCIVEK in People with Hepatitis C Following a Liver Transplant

-- By the end of 2011, Vertex expects to initiate the first Phase 2b clinical study of INCIVEK combination treatment in people who have recurrent hepatitis C following a liver transplant. The 2-part trial will evaluate approximately 80 people.

Phase 1 Trials to Begin for ALS-2200 and ALS-2158

-- Vertex and Alios plan to advance ALS-2200 and ALS-2158 into clinical development beginning later this year. The first Phase 1 study is expected to begin by year-end for ALS-2200, followed by a study of ALS-2158 in early 2012. The studies will evaluate healthy volunteers followed by people with hepatitis C. The goal of these studies is to generate safety, pharmacokinetic and viral kinetic data to support the potential evaluation of either or both compounds in all-oral treatment regimens for hepatitis C.

Additional information on INCIVEK, including important safety information, appears at the end of this release.

Cystic Fibrosis (CF)

U.S. and E.U. Applications for Approval of KALYDECO (VX-770, ivacaftor) Complete

-- Last week, Vertex submitted an NDA to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for KALYDECO, Vertex's cystic fibrosis transmembrane conductance regulator protein (CFTR) potentiator. Vertex requested Priority Review from the FDA and has received agreement from the EMA for accelerated assessment of KALYDECO in Europe.

Phase 2 Combination Trial of KALYDECO and VX-809 Enrolling Patients in Part 2

-- Vertex today announced the start of the second part of a Phase 2 clinical trial to evaluate combination regimens of KALYDECO and VX-809, a CFTR corrector, in people with the most common mutation in CF, known as F508del. Part Two of this trial will evaluate dosing of VX-809 alone for four weeks followed by dosing of KALYDECO and VX-809 in combination for four weeks. The study is expected to evaluate multiple dose levels of VX-809, including doses higher than those studied in the first part of the trial. The study is expected to enroll approximately 100 people with CF who have one copy or two copies of the F508del mutation. Similar to Part One, the primary goals of the second part of the trial are to evaluate safety and tolerability and the effect of the combination of KALYDECO and VX-809 on CFTR function as measured by sweat chloride. Lung function will be measured as a secondary endpoint. Patient screening for this study is underway.

KALYDECO and VX-809 Presentations at the North American Cystic Fibrosis Conference

-- Nine abstracts were accepted for presentation at the 2011 North American Cystic Fibrosis Conference (NACFC), being held in Anaheim, CA, November 3-5. Complete 48-week data from the Phase 3 ENVISION study of KALYDECO in children ages 6 to 11 years will be presented for the first time, as will data from a subset of patients in the open-label PERSIST extension study who had completed 48 weeks of treatment (placebo or KALYDECO) in one of the KALYDECO Phase 3 trials (STRIVE or ENVISION). Data from the first 12 weeks of the rollover study in patients who completed the STRIVE study and entered PERSIST will be presented at the meeting. In addition, complete data from the first part of the Phase 2 study combining KALYDECO and VX-809 will be presented for the first time.

Additional Studies of KALYDECO Planned for 2012

-- Pediatric Study: Vertex remains on track to initiate a Phase 2 study of KALYDECO dosed as monotherapy in children ages 2 through 5 in 2012. This will be the first study to evaluate a pediatric formulation of KALYDECO in children with the G551D mutation as young as two years of age.

-- Other CFTR Mutations: Also in 2012, Vertex plans to begin evaluation of KALYDECO monotherapy in people with certain other gating mutations (not G551D) and in mutations that result in some residual function of the defective CFTR protein on the cell surface. Vertex is in discussions with global regulatory agencies regarding the design of these studies and intends to provide additional information upon the initiation of the first study in these additional mutations.

First Study of VX-661 Planned for First Quarter of 2012

-- In addition to the ongoing Phase 2 study of KALYDECO and VX-809, Vertex also plans to begin Phase 2 development of VX-661, another CFTR corrector, in the first quarter of 2012. VX-661 is expected to be evaluated as monotherapy followed by dosing of VX-661 in combination with KALYDECO in people with two copies of the F508del mutation.

Rheumatoid Arthritis

350-patient Phase 2b Study of VX-509 To Begin by Early 2012 for Rheumatoid Arthritis

-- In September, Vertex announced data from a Phase 2 proof-of-concept clinical trial of the oral JAK3 inhibitor VX-509 in people with moderate to severe rheumatoid arthritis (RA). Based on these data, Vertex plans to begin a six-month Phase 2b study of VX-509 in RA by early 2012. This study will evaluate once-daily (QD) and twice-daily (BID) doses of VX-509 in combination with methotrexate, a commonly prescribed disease-modifying antirheumatic drug (DMARD) for RA that is frequently used in combination with other RA medicines. The study is expected to enroll approximately 350 people with moderate to severe RA.

Epilepsy

400-patient Phase 2b Study of VX-765 To Begin by Year-end for Epilepsy

-- Earlier this year, Vertex announced results from a Phase 2 study of VX-765 in people with treatment-resistant epilepsy. Based on these results, Vertex plans to initiate an additional Phase 2 study to evaluate longer dosing of VX-765 in approximately 400 people with treatment-resistant epilepsy. The trial is expected to begin by the end of this year.

Influenza:

Phase 1 Development Underway for VX-787

-- In September, Vertex began clinical development of VX-787 in a Phase 1 study in healthy volunteers. VX-787 is an investigational medicine that is designed to treat influenza A, including recent H1 (pandemic) and H5 (avian) influenza strains. VX-787 is the first of a new class of molecules that aims to treat influenza in a way that is distinct from neuraminidase inhibitors, the current standard of care for the treatment of influenza, and from other previous approaches to the treatment of influenza.

-- Phase 1 development in healthy volunteers is ongoing, and Vertex plans to begin evaluation of VX-787 in influenza infection as part of a Phase 2a proof-of-concept trial in mid-2012.

Third Quarter Financial Results

"Our financial performance in the third quarter was driven by the successful launch of INCIVEK, enabling Vertex to be profitable and cashflow positive in the first full quarter after INCIVEK was available," said Ian Smith, Executive Vice President and Chief Financial Officer. "We remain committed to reinvesting in our broad pipeline and to the creation of significant earnings, which we believe will deliver the greatest value for patients, the company and shareholders."

Total Revenues: Total revenues for the quarter ended September 30, 2011 were $659.2 million, compared with $23.8 million in total revenues for the third quarter of 2010. The increase in total revenues is primarily a result of INCIVEK net revenues of $419.6 million and $200.0 million in milestone revenues earned from Vertex's collaborator Janssen in the third quarter.

INCIVEK Revenues: For the quarter ended September 30, 2011, Vertex reported $419.6 million in net revenues of INCIVEK, which were recorded on an ex-factory basis and reflect the first full quarter of INCIVEK sales following approval on May 23, 2011. Net revenues of INCIVEK for the second quarter of 2011 were $74.5 million.

Cost of Product Revenues: Cost of product revenues for the quarter ended September 30, 2011 was $35.3 million, which principally reflects royalty expenses owed to third parties on the sale of INCIVEK.

Research and Development (R&D) Expenses: R&D expenses for the quarter ended September 30, 2011 were $189.1 million, including $18.7 million in stock-based compensation expense, compared to $170.4 million, including $17.0 million in stock-based compensation expense, for the third quarter of 2010. These expenses reflect the company's continued investment in its research and development pipeline, including preparation for the initiation of multiple clinical trials planned to begin by early 2012.

Sales, General and Administrative (SG&A) Expenses: SG&A expenses for the quarter ended September 30, 2011 were $110.7 million, including $10.8 million in stock-based compensation expense, compared to $48.9 million, including $6.8 million in stock-based compensation expense, for the third quarter of 2010. This increase reflects the expansion of the company's commercial organization to support both INCIVEK and KALYDECO and costs related to the commercial launch of INCIVEK.

GAAP and Non-GAAP Net Income (Loss) Attributable to Vertex: For the quarter ended September 30, 2011, the company's GAAP net income attributable to Vertex was $221.1 million, or $1.02 per diluted share, compared to a GAAP net loss attributable to Vertex for the quarter ended September 30, 2010 of $209.0 million, or $1.04 per diluted share.

The non-GAAP net income attributable to Vertex for the quarter ended September 30, 2011 was $151.2 million, or $0.70 per diluted share, compared to a non-GAAP net loss of $174.6 million, or $0.87 per diluted share, for the quarter ended September 30, 2010. The non-GAAP net income for the third quarter of 2011 and the third quarter non-GAAP net loss for the third quarter of 2010 excludes stock-based compensation expense, restructuring expense (credit), any revenues and expenses related to certain September 2009 financial transactions, any intangible asset impairment charge, net of tax, and items related to Vertex's collaboration with Alios. The increase in the third quarter 2011 non-GAAP net income attributable to Vertex resulted principally from increased revenues related to the sale of INCIVEK.

Cash Position: At September 30, 2011, Vertex had $658.7 million in cash, cash equivalents and marketable securities, compared to cash, cash equivalents and marketable securities at June 30, 2011 of $593.5 million.

This section contains forward-looking guidance about the financial outlook for Vertex Pharmaceuticals.

Vertex is today reiterating its guidance for 2011 total operating expenses, excluding cost of revenues, stock-based compensation expense and intangible asset impairment charge, of $960 to $980 million, as provided on July 28, 2011.

Go here for the full press release.

Vertex to Present New Data from Hepatitis C Development Program at AASLD Annual Meeting

Vertex to Present New Data from Hepatitis C Development Program at AASLD Annual Meeting

- Late-Breaker Presentations Include Phase 2 Data from INCIVEK-Based Combination Regimen in HIV/HCV Co-Infection and Short Duration Treatment with a Four-Drug Regimen Including INCIVEK and VX-222 -


CAMBRIDGE, Mass., Sep 30, 2011 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated VRTX +4.67% today announced that abstracts from its hepatitis C program, including two late-breaking posters from studies of INCIVEK(TM) (telaprevir) tablets and VX-222, were accepted for presentation at The Liver Meeting(R), the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, November 4-8, 2011.

New data, including sustained viral response (SVR, or viral cure) results, from a Phase 2 study evaluating short durations of 12- and 24-week regimens of VX-222 in combination with INCIVEK (in-SEE-veck), pegylated-interferon and ribavirin in people with genotype 1 chronic hepatitis C who were new to treatment will be presented for the first time. Additionally, new data from a Phase 2 study evaluating INCIVEK combination treatment in people co-infected with genotype 1 chronic hepatitis C and human immunodeficiency virus (HIV) will be presented at the meeting. All people in this study were new to hepatitis C treatment.

"INCIVEK combination therapy has successfully increased viral cure rates and shortened total treatment time for the majority of people with hepatitis C who are being treated for the first time, but we have more to do," said Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. "Our ongoing research is aimed at further improving treatment for hepatitis C by exploring the use of INCIVEK among those in critical need of more effective medicines and evaluating combinations, including some without interferon, that may offer higher cure rates and shorter treatment times."

The accepted abstracts are now available on the AASLD website at https://www.aasld.org/lm2011 .

INCIVEK Oral Presentations

1. #31: "Efficacy and safety of telaprevir-based regimens in cirrhotic patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure: subanalysis of the REALIZE Phase III study." November 6, 2011, 3:00 p.m. PDT.

2. #32: "Predictors of virologic response with telaprevir-based combination treatment in HCV genotype 1-infected patients with prior peginterferon/ribavirin treatment failure: post-hoc analysis of the Phase III REALIZE study." November 6, 2011, 3:15 p.m. PDT.

3. #35: "Retreatment with telaprevir/Peg-IFN/RBV after a short exposure to telaprevir in Phase I studies: interim results from a Phase IIIb rollover trial (C219)." November 6, 2011, 4:00 p.m. PDT.

4. #248: "Follow-up of SVR Durability and Viral Resistance in Patients with Chronic Hepatitis C Treated with Telaprevir-Based Regimens: Interim Analysis of the EXTEND Study." November 8, 2011, 11:00 a.m. PDT.

Vertex Late-Breaking Poster Presentations

1. #LB-8: "Telaprevir Combination with Peginterferon Alfa-2a/Ribavirin in HCV/HIV Coinfected Patients: 24-Week Treatment Interim Analysis." November 7, 2011.

2. #LB-14: "VX-222/telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin in Treatment-naive Genotype 1 HCV Patients Treated for 12 Weeks: ZENITH Study, SVR12 Interim Analysis." November 7, 2011.

Vertex Poster Presentations

1. #943: "Projections Using Decision-Analytic Modeling of Long-Term Clinical Value of Telaprevir for the Treatment of HCV Patients who had Failed Prior Peginterferon/Ribavirin Treatment." November 6, 2011.

2. #1328: "Summary of Clinical Virology Findings from Clinical Trials of Telaprevir." November 7, 2011.

3. #1331: "Different likelihood of achieving SVR on a telaprevir-containing regimen among null responders, partial responders and relapsers irrespective of similar responses after a peginterferon/ribavirin 4-week lead-in phase: REALIZE study subanalysis." November 7, 2011.

4. #1368: "Impact of anemia and ribavirin dose reduction on SVR to a telaprevir-based regimen in patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure in the Phase III REALIZE study." November 7, 2011.

5. #1369: "Impact of insulin resistance on virologic response to a telaprevir-based regimen in patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure: post-hoc analysis of the REALIZE Phase III study." November 7, 2011.

6. #2105: "Sustained Virologic Response Rates and Viral Resistance Profiles Were Similar in Patients Treated with a Telaprevir-Based Regimen Regardless of Liver Fibrosis Stage." November 8, 2011.

About INCIVEK

INCIVEK is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 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 but who did not achieve a sustained viral response or viral cure (relapsers, partial responders and null responders).

INCIVEK (750 mg) is given as two 375 mg tablets three times daily for 12 weeks in combination with pegylated-interferon and ribavirin. Each monthly package of INCIVEK contains four weekly boxes that include daily blister strips. After the first 12 weeks, all patients stop receiving INCIVEK and continue treatment with pegylated-interferon and ribavirin alone for an additional 12 weeks or 36 weeks of treatment. With INCIVEK combination therapy, more than 60 percent of people treated for the first time, as well as those who relapsed after previous therapy, are expected to complete all treatment in 24 weeks. All other patients receive a total of 48 weeks of treatment.

Rash and anemia are the most serious side effects associated with INCIVEK, which led to treatment discontinuation in about 1 percent of people in clinical studies. The most common side effects reported with INCIVEK combination treatment include fatigue, itching, nausea, diarrhea, vomiting, anal or rectal problems, and taste changes.

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(R) 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 will be known as Telavic(R).

About VX-222

VX-222 is an oral medicine in development that is a non-nucleoside inhibitor of the HCV NS5B polymerase. VX-222 is being evaluated in a Phase 2 study in combination with INCIVEK and ribavirin, with and without pegylated-interferon. Vertex retains worldwide commercial rights to VX-222.

IMPORTANT SAFETY INFORMATION

Indication

INCIVEK(TM) (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.

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 rash and anemia. 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 .

INCIVEK(TM) is a trademark of Vertex Pharmaceuticals Incorporated.

PEGASYS(R) and COPEGUS(R) are registered trademarks of Hoffmann-La Roche.

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)

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 statements regarding Vertex's aim to further improve treatment for hepatitis C by exploring the use of INCIVEK among those in critical need of more effective medicines and evaluating combinations that may offer higher cure rates and shorter treatment times. 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, future scientific, clinical, competitive or other market factors may adversely affect the potential for INCIVEK-based therapies 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.

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, 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.

(VRTX-GEN)

(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 March 21, 2011.

(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 March 21, 2011.

(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 March 21, 2011. 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.

SOURCE: Vertex Pharmaceuticals Incorporated


Vertex Pharmaceuticals Incorporated
Media:
Dawn Kalmar, 617-444-6992
mediainfo@vrtx.com
or
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
or
Matthew Osborne, 617-444-6057
or
Patient Inquiries: 1-855-837-8394

Interim Data from Phase 2 Study of Combination Regimen Including VX-222 and INCIVEK™ Suggest Potential to Treat Genotype 1 Hepatitis C in as few as 12 Weeks and No More Than 24 Weeks

(Interim analysis of this 30 patient Phase II trial today designed to assess the safety, tolerability and efficacy of multiple 12- and 24-week response-guided treatment regimens with Vertex's polymerase inhibitor VX-222 (400 mg or 100 mg), and Telaprevir plus Peg/ Riba in genotype1 treatment naive subjects. Results showed that 50 percent of people (15/30) in the study who received VX-222 (400 mg) in combination with INCIVEK, pegylated-interferon and ribavirin were eligible to stop all treatment at week 12, and 93 percent (14/15) had SVR12. Patients from the VX-222 (400 mg) treatment arm who were not eligible to stop all treatment at week 12 received an additional 12 weeks of pegylated-interferon and ribavirin alone for 24 total weeks of treatment. The hepatitis C virus was undetectable in 100 percent (13/13) of these patients at the end of 24 weeks. In this study, VX-222, Telaprevir and ribavirin were given twice daily (BID). Interim safety results from the four-drug treatment arms showed that mild gastrointestinal symptoms and mild fatigue were the most frequently reported adverse events. Side effects consistent with the known safety profile of INCIVEK combination treatment also were observed. Leaves one to wonder what sort of results we'd see with Telaprevir in combination with the recently purchased nucleoside analogs from Aliso Pharmaceuticals)

BusinessWire · Jul. 26, 2011 | Last Updated: Jul. 26, 2011 7:30 AM ET

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced interim results from ZENITH, an ongoing Phase 2 study designed to assess the safety, tolerability and efficacy of multiple 12- and 24-week response-guided treatment regimens with VX-222 (400 mg or 100 mg), its lead polymerase inhibitor in development, in combination with INCIVEK™ (telaprevir) tablets, pegylated-interferon and ribavirin in people with genotype 1 chronic hepatitis C who were new to treatment. This is an interim analysis from patients in the four-drug treatment arms and was conducted after these patients completed their assigned treatment. Results showed that 50 percent of people (15/30) in the study who received VX-222 (400 mg) in combination with INCIVEK, pegylated-interferon and ribavirin were eligible to stop all treatment at week 12, and 93 percent (14/15) of these patients had undetectable hepatitis C virus 12 weeks after treatment ended (sustained viral response 12, or SVR12). Patients from the VX-222 (400 mg) treatment arm who were not eligible to stop all treatment at week 12 received an additional 12 weeks of pegylated-interferon and ribavirin alone for 24 total weeks of treatment. The hepatitis C virus was undetectable in 100 percent (13/13) of these patients at the end of 24 weeks. In this study, VX-222, INCIVEK and ribavirin were given twice daily (BID). Interim safety results from the four-drug treatment arms showed that mild gastrointestinal symptoms and mild fatigue were the most frequently reported adverse events. Side effects consistent with the known safety profile of INCIVEK combination treatment also were observed.

“The results from this study are the first to show the potential for a combination of multiple direct-acting antiviral medicines to help people with hepatitis C clear the virus with as few as 12 and no more than 24 weeks of treatment,” said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. “We look forward to additional data from this study, including data from the ongoing all-oral treatment arms, which will guide our future development plans with the goal of further improving treatment.”

ZENITH is an ongoing Phase 2 study that initially enrolled 106 people with genotype 1 chronic hepatitis C and began with four treatment arms designed to evaluate multiple response-guided treatment regimens with VX-222, Vertex’s lead polymerase inhibitor in development, in combination with INCIVEK, Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin), three medicines approved to treat hepatitis C. In this study, VX-222, INCIVEK and ribavirin were given twice daily. 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. Additional results from this study will be submitted for presentation at an upcoming medical meeting.

Arms A (n=18) and B (n=29) were designed to evaluate all-oral, two-drug combination regimens of VX-222 (400 mg or 100 mg) and INCIVEK (1,125 mg). Data presented in March at The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the Study of the Liver (EASL), in Berlin, Germany, showed significant initial antiviral activity in people who were treated with VX-222 (400 mg) and INCIVEK. However, these treatment arms were discontinued due to a pre-defined stopping rule related to viral breakthrough. Arms C (n=29) and D (n=30) are ongoing and are designed to evaluate four-drug combination regimens of VX-222 (400 mg or 100 mg), INCIVEK (1,125 mg), pegylated-interferon and ribavirin.

Data announced today are from the four-drug treatment arms (Arms C and D). In these two arms, patients were assigned to take all four medicines for the first 12 weeks of treatment. People who had undetectable hepatitis C virus levels in the blood (HCV RNA) at weeks two and eight of treatment were eligible to stop all treatment at week 12. In this study, the amount of hepatitis C virus in the blood was measured by the Roche COBAS® Taqman HCV test (<10 IU/mL undetectable). People who did not meet these criteria were assigned to receive 24 total weeks of treatment: 12 weeks of the four-drug combination regimen followed by 12 weeks of pegylated-interferon and ribavirin alone. This interim analysis includes SVR12 results for the people who were eligible for and completed 12 total weeks of treatment and end-of-treatment results for the people who were assigned to and completed 24 total weeks of treatment.

ZENITH: Interim Analysis
SVR12 in people who
were eligible for and
completed 12 total
weeks of treatment
Undetectable hepatitis C
virus in people who were
assigned to and
completed 24 weeks of
treatment
Undetectable
hepatitis C virus at
week 24 for all
patients (intent-to-
treat analysis)

VX-222 (400 mg), INCIVEK,
pegylated-interferon and ribavirin*
(n=30)
93%
(14/15)+
100%
(13/13)
90%
(27/30)

VX-222 (100 mg), INCIVEK,
pegylated-interferon and ribavirin**
(n=29)
82%
(9/11) ++
93%
(13/14)^
83%
(24/29)

SVR12: undetectable hepatitis C virus 12 weeks after treatment ended.



*50 percent (15/30) had undetectable hepatitis C virus at weeks 2 and 8 and were eligible to stop all treatment at week 12. Two people in the VX-222 (400 mg) treatment arm discontinued treatment before week 12 and did not achieve SVR12.



**38 percent (11/29) had undetectable hepatitis C virus at weeks 2 and 8 and were eligible to stop all treatment at week 12. Four people in the VX-222 (100 mg) treatment arm discontinued treatment before week 12 and two of them achieved SVR12.



+One person in the 12-week VX-222 (400 mg) treatment arm relapsed.

++Two people in the 12-week VX-222 (100 mg) treatment arm relapsed.



^24-week end-of-treatment data are not available for one patient.


Two additional treatment arms (E and F) were added to the study to evaluate a three-drug, all-oral, interferon-free regimen of VX-222 (400 mg), INCIVEK and ribavirin. Enrollment in these treatment arms is expected to be complete by the end of the third quarter of 2011. Arm E will evaluate people with genotype 1b chronic hepatitis C and Arm F will evaluate people with genotype 1a chronic hepatitis C. Vertex expects to report data from the all-oral treatment arms in the first half of 2012.

Interim Safety and Tolerability Results from the Four-drug Treatment Arms

The most frequent adverse events observed in the four-drug treatment arms were fatigue, nausea, diarrhea, anemia, pruritis (itchiness) and rash. The majority of events were mild or moderate. Mild diarrhea occurred more frequently in the VX-222 (400 mg) treatment arm. The majority of people in the study did not use medication to control diarrhea. There were no treatment discontinuations due to diarrhea. Six patients discontinued treatment due to adverse events; three each from the 400 mg and 100 mg treatment arms. Two people from each arm discontinued treatment before week 12 and one person in each arm discontinued treatment between weeks 12 and 24 while they were receiving pegylated-interferon and ribavirin alone.

About INCIVEK and VX-222

INCIVEK (in-SEE-veck) is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. In May 2011, INCIVEK was approved by the U.S. Food and Drug Administration (FDA) for a broad group of 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 but who did not achieve a SVR, or viral cure (relapsers, partial responders and null responders).

VX-222 is an oral medicine in development that is a non-nucleoside inhibitor of the HCV NS5B polymerase. VX-222 is currently being evaluated in combination with INCIVEK, pegylated-interferon and ribavirin in a Phase 2 study. Vertex has worldwide commercial rights for VX-222.

Vertex developed telaprevir in collaboration with Tibotec Vicro-Virology BVBA, one of the Janssen Pharmaceutical companies of Johnson & Johnson, and Mitsubishi Tanabe Pharma. Vertex is commercializing telaprevir in North America, where it is known as INCIVEK. Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In July 2011, Janssen announced that the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for INCIVO (telaprevir). Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.

INCIVEK™ is a trademark of Vertex Pharmaceuticals Incorporated.

PEGASYS®, COPEGUS® and Roche COBAS® Taqman HCV test are registered trademarks of Hoffmann-La Roche.

Indication

INCIVEKTM (telaprevir) tablets 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, you should not take INCIVEK combination treatment if you are pregnant or may become pregnant, or if you are a man with a sexual partner who is pregnant.

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 you cannot take with INCIVEK combination treatment. Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements.

INCIVEK can cause serious side effects including rash and anemia. 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. Tell your healthcare provider about any side effect that bothers you or doesn’t go away.

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

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 Chronic hepatitis C is the leading cause of liver cancer and 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.11

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 statements regarding (i) the potential for a combination of multiple direct-acting antiviral medicines to treat genotype 1 hepatitis C in as few as 12 weeks and no more than 24 weeks; (ii) additional results from the study being submitted for presentation at an upcoming medical meeting; (iii) additional data from this study, including data from the ongoing all-oral treatment arms, guiding our future development plans with the goal of further improving treatment; (iv) the design of Arm E and Arm F of the study and the expectation that enrollment in these arms will be completed by the end of the third quarter of 2011; and (v) the expectation that Vertex will report data from the all-oral treatment arms in the first half of 2012. 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 interim data presented in this press release may not be predictive of the final outcomes from this clinical trial; the outcomes from additional arms in this clinical trial and/or from any future clinical trials of telaprevir/VX-222 may not be favorable; future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir/VX-222-based therapy 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.

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, 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.

(VRTX - GEN)

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 March 21, 2011.

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 March 21, 2011.

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 March 21, 2011. 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.


Contacts

Vertex Pharmaceuticals Incorporated
Media:
Dawn Kalmar, 617-444-6992
or
Amy Pasqua, 617-444-6992
or
Zachry Barber, 617-444-6992
mediainfo@vrtx.com
or
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
or
Matthew Osborne, 617-444-6057
or
Patient Inquiries: 1-855-837-3894

Vertex Ends Part of Telaprevir Combination Drug Study for Hepatitis C

The cause of this discontinuation of the Q12h TVR + VX-222 without peg and riba was viral breakthrough. Peg and ribavirin isn't going anywhere soon.

Vertex Pharmaceuticals Inc. discontinued one part of a clinical study evaluating its hepatitis C treatments.

Vertex is halting a test of its medicine telaprevir in combination with its other experimental therapy called VX-222, the Cambridge, Massachusetts-based company said in a statement. Vertex will continue testing telaprevir and VX-222 in groups of patients who will receive it with one or two drugs given as a combination treatment. The study is the second of three phases of clinical tests typically required for U.S. approval.

Telaprevir, which Vertex is developing with Johnson & Johnson of New Brunswick, New Jersey, is the company’s most advanced experimental drug. There are no medicines available for hepatitis C patients who don’t respond to standard drugs. Howard Liang, an analyst at Leerink Swann & Co. in Boston, estimated telaprevir may generate $2.6 billion annually by 2013.

“This trial has provided important information regarding telaprevir and VX-222-based combination regimens, and three of the five treatment arms are proceeding as planned,” Robert Kauffman, Vertex’s chief medical officer, said in the statement.

Hepatitis C often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver. It affects about 4 million Americans and 200 million people worldwide, according to the National Institutes of Health.

Vertex ended another two-drug arm of the study in October.

Vertex fell 1.1 percent at 5:06 p.m. New York time in extended trading after gaining 76 cents, or 2.1 percent, to $36.32 at the close of the Nasdaq Stock Market.

To contact the reporter on this story: David Olmos in San Francisco at dolmos@bloomberg.net

To contact the editor responsible for this story: Reg Gale at Rgale5@bloomberg.net