Telaprevir
Vertex is developing telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America. Through its affiliate, Janssen, 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  

Final data from the REALIZE trial
Phase 3 REALIZE study enrolled 662 patients to evaluate people with genotype 1 chronic hepatitis C whose prior treatment with pegylated-interferon and ribavirin was unsuccessful either because they relapsed, had a partial response or had a null response.
Data from the study showed that people in each of these subgroups who were treated with telaprevir-based combination therapy achieved superior rates of sustained viral response (SVR, or viral cure) compared to those treated with pegylated interferon and ribavirin alone.

The Subgroups; relapsed, partial response, null response.

All major subgroups achieved significantly higher viral cure rates with telaprevir-based therapy compared to pegylated interferon and ribavirin:

86% vs. 24% in prior relapsers
57% vs. 15% in prior partial responders 
31% vs. 5% in prior null responders.

No clinical benefit was observed in delaying telaprevir therapy by four weeks (lead-in) compared to starting telaprevir, pegylated-interferon and ribavirin simultaneously.

Defined in the study as;
Lead-in = four weeks of only standard therapy (pegylated-interferon and ribavirin) followed by telaprevir in combination with pegylated interferon and ribavirin for 12 weeks followed by 32 weeks of pegylated interferon and ribavirin alone.

Simultaneously = 12 weeks of telaprevir , pegylated-interferon alfa-2a & ribavirin, followed by 36 weeks of PEG & RBV alone.

Summary of REALIZE Results

REALIZE is the only Phase 3 hepatitis C study to date of a direct-acting antiviral medicine in development that was designed to evaluate people whose prior treatment was unsuccessful, including those who had a null response.

*boceprevir also had a trial deemed the RESPOND - 2 study which included prior non-responders and relapsers

Results from the phase III REALIZE trial indicated that, among prior relapsers, (SVR) sustained response rates with two telaprevir-containing regimens were 83% and 88%, compared with 24% for peginterferon alfa-2a and ribavirin plus placebo. Lower sustained viral response rates were seen in patients who previously showed partial or no response to the two standard drugs, but they were still significantly better than in the placebo group (41% in both telaprevir arms versus 9% in the control group

Understanding The Dose Schedule and Different Arms Of The Study

The primary endpoint of the REALIZE study was SVR in each of the two telaprevir treatment arms(TVR-based Simultaneous Start Arm and TVR-based Lead-In Arm ) compared to the control arm and for the three groups (relapsed, partial response,null response) of people included in the study.
The total treatment time for all patients in REALIZE was 48 weeks.

In this study, patients were randomized 2:2:1 to two telaprevir-based treatment arms (simultaneous or lead-in) or a control arm of 48 weeks of pegylated interferon and ribavirin alone.

TVR-based = Patients in the telaprevir treatment arms received a total of 12 weeks of telaprevir-based combination therapy.

TVR-based Simultaneous Start Arm  or T12/PR48 = For those in the simultaneous start arm, the telaprevir-based combination was followed by an additional 36 weeks of pegylated-interferon and ribavirin alone.
+Simultaneous start: 12 weeks of telaprevir (750 mg, q8h), Pegasys (PEG, pegylated-interferon alfa-2a) & Copegus (RBV, ribavirin), followed by 36 weeks of PEG & RBV alone.

TVR-based Lead-In Arm or LIT12/PR48 =  In the lead-in arm, patients received four weeks of pegylated interferon and ribavirin followed by telaprevir in combination with pegylated interferon and ribavirin for 12 weeks followed by 32 weeks of pegylated interferon and ribavirin alone. 
++Lead-in: 4 weeks of PEG & RBV alone followed by 12 weeks of telaprevir (750 mg, q8h), PEG & RBV, followed by 32 weeks of PEG & RBV alone. There was no clinical benefit with the use of a four-week lead in with no significant improvement in SVR rates and no significant reduction in virologic failure and relapse rates in the lead-in start arm compared to the simultaneous start arm.

Control Arm or Pbo/PR48 = Control: 48 weeks of pegylated interferon and ribavirin alone *12 weeks of placebo
+++Control: 12 weeks of placebo, w-PEG & RBV, followed by 36 weeks of Peg & RBV alone.

Safety and Tolerability Information for the Phase 3 Studies of Telaprevir

Among the most common adverse events during any treatment phase, fatigue occurred in 55% of the T12/PR48 patients, 50% of the LIT12/PR48 group, and 40% of the Pbo/PR48 group. Frequencies of pruritus were similar.

Anorectal symptoms (anal pruritus, anorectal discomfort, hemorrhoids) were reported in 28%, 22%, and 8% of the T12/PR48, LIT12/PR48, and Pbo/PR48 groups, respectively.

For each of these adverse events, and for anemia, rash, nausea and diarrhea, the incidence was more than 10% greater in the T12/PR48 arm than in the Pbo/PR48 arm.

Discontinuations of any study drug during telaprevir treatment occurred in 29% of patients. Rash and anemia were the most common adverse effects associated with drug stoppage.

The safety and tolerability results of the telaprevir-based combination regimens were consistent across the Phase 3 studies. The most common adverse events were fatigue, pruritis [itching], nausea, headache, rash, anemia, flu-like symptoms, insomnia and diarrhea with the majority being mild to moderate. Rash and anemia occurred more frequently in the telaprevir-based treatment arms compared to the control group.

Rash was primarily characterized as eczema-like, manageable and resolved upon stopping telaprevir. More than 90 percent of rash was mild to moderate and primarily managed with the use of topical corticosteroids and/or antihistamines. Anemia was primarily managed by reducing the dose of ribavirin.

To optimize each patient's opportunity to achieve viral cure in the Phase 3 studies, sequential discontinuation of the medicines was recommended as a strategy to manage certain adverse events. This strategy allowed patients to continue on pegylated-interferon and ribavirin after stopping telaprevir. Discontinuation of all medicines due to either rash or anemia during the telaprevir/placebo treatment phase was 1 percent to 3 percent in the telaprevir treatment arms.

From NATAP ; Includes slides and commentary from Jules Levin
REALIZE Trial Final Results: Telaprevir-based Regimen for Genotype 1 Hepatitis C Virus Infection in Patients with Prior Null Response, Partial Response or Relapse to Peginterferon/Ribavirin

Telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin Increased Sustained Virologic Response Rates in Treatment-naïve Patients Regardless of Race or Ethnicity

Telaprevir IL28B

About IL28B
IL28B is a gene related to the interferon system. A genetic
region near the IL28B gene is referred to as an IL28B genotype.
There are three variations of IL28B genotypes: CC, CT or TT. These
variations have been associated with a person's response to
treatment for hepatitis C with pegylated-interferon and ribavirin.
Studies have shown that people with the CC variation respond better
to treatment with pegylated-interferon and ribavirin than those
with the CT or TT variations. The CC variation is more frequent in
Caucasians compared to African Americans (39 percent versus 16
percent), which may partially explain the lower response to
treatment observed among African Americans in most clinical trials
of pegylated-interferon and ribavirin.

From ;
Ira Jacobson, M.D., Chief of the Division of
Gastroenterology and Hepatology at New York-Presbyterian
Hospital/Weill Cornell Medical Center, and the Vincent Astor
Distinguished Professor of Medicine at Weill Cornell Medical
College and principal investigator for the ADVANCE study.
“Doctors sometimes use IL28B genotype status to decide
which patients should be treated with currently available medicines
because people with the CT and TT variations of IL28B tend to have
substantially lower viral cure rates compared to those with the CC
variation, In this study, telaprevir was associated with a substantial
improvement over currently available medicines, regardless of IL28B
status, and the greatest improvement was observed in patients with
the CT and TT variations.”

New data from retrospective analyses that evaluated the relationship between
variations at the IL28B gene and a patient's response to treatment
with telaprevir in combination with pegylated-interferon and
ribavirin from two of its pivotal Phase 3 studies (ADVANCE and
REALIZE) for a group of people who were tested for IL28B genotype.
These analyses showed that people in these studies had substantial
improvements in sustained viral response (SVR, or viral cure) rates
across all IL28B genotypes (CC, CT or TT) for those treated with
telaprevir-based combination therapy compared to those treated with
pegylated-interferon and ribavirin alone.

90% of people with the ˜CC' variation of IL28B who
were new to treatment and received a telaprevir-based regimen
achieved a viral cure, 78% of them were eligible to stop all
treatment at 24 weeks -

- Nearly three-fold improvement in viral cure rates was
observed among people with the ˜CT' and ˜TT' variations
compared to the control group, regardless of prior treatment
experience -

Better Then SOC; Improvements in Viral Cure Rates W-Telaprevir-Based TX Regardless of IL28B Genotype Status

NATAP ; Similar SVR Rates in IL28B CC, CT or TT Prior Relapser, Partial- or Null-responder Patients Treated with Telaprevir/Peginterferon/Ribavirin: Retrospective Analysis of the REALIZE Study -

Telaprevir Resistance
RESISTANCE: the mutation of a microorganism in such a way that it loses its sensitivity to a drug; a resistant organism can function and replicate despite the drug's presence.

Over 40 posters were presented at the EASL with data highlighting resistance in patients who fail to achieve SVR when treating with the new protease inhibitors, you can view them here.

Excerpt from the EASL press release New data suggests liver experts should exercise caution when prescribing novel antiviral HCV drugs".

Data presented at the International Liver CongressTM highlight the fact that new novel antiviral compounds for the treatment of hepatitis C virus (HCV) must be prescribed and monitored by experts and specialists to ensure resistance is minimised.

Several studies observed the rapid onset of HCV resistance in patients treated with NS3-protease, NS5b-polymerase and NS5a inhibitors. Although these direct anti-virals are effective in both treatment-naive HCV patients and those who've been previously unresponsive to current treatment options, the development of resistant viral variants may cause problems in the future. In fact, two studies found HCV strains resistant to novel antiviral compounds pre-existed in patients who had never previously been exposed to the new antiviral compounds. In these patients, the variants were selected out by treatment.

Professor Heiner Wedemeyer, EASL's Secretary General, said: "While the regulatory approval of these new treatments is a highly anticipated milestone in HCV therapy, these studies show that care must be taken in the prescription and use of the new compounds. What we want to avoid is a rapid spread of HCV resistance within the patient population, which could drastically lower the effectiveness of the new drugs."

Additional information is available at CCO a website which provides an expert analysis on data presented at the EASL; .Telaprevir-Resistant HCV Variants Present at Time of Treatment Failure Replaced by Wild-Type Virus Over Time in Majority of Patients
*To view the site free registration is required.

Slides; Evolution of Treatment-Emergent Variants in Telaprevir Phase 3 Clinical Trials -

Of interest;
An older study from the 2010 AASLD conference; Telaprevir Resistance Disappears in 89% of Patients: Long-Term Follow-up of Patients with Chronic Hepatitis C Treated with Telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin: Interim Analysis from the EXTEND Study

Boceprevir
The released data on boceprevir happened to coincide with the publication of the primary data from the pivotal Phase III studies of VICTRELIS/Merck in The New England Journal of Medicine.

New England Journal Study
Boceprevir for Previously Treated Chronic HCV Genotype 1 Infection
B.R. Bacon and Others

Video On The Study Of Previously Treated Patients

Merck, the manufacturer of boceprevir, funded both studies, which are published in the March 31 issue of the New England Journal of Medicine.

"Boceprevir, a protease inhibitor, along with peginterferon and ribavirin increases response rates in previously untreated patients," said Dr. Raj Reddy, co-researcher of one of the studies and director of hepatology and medical director of liver transplantation at the University of Pennsylvania in Philadelphia.

"Also, with this new strategy you have the potential of reducing the duration of therapy, from 48 weeks to 28 weeks," he added.

"We have turned the corner, a bit, and we have a combination treatment that is likely to be more effective in more people," he said.

For his study, 1,097 people, 159 of whom were black, who had not been treated for hepatitis C were randomly assigned to one of three groups. All groups were treated with peginterferon and ribavirin. After four weeks, one group also received a placebo for 44 weeks; another group had boceprevir added to their treatment for 24 weeks. The third group was given the three drugs for 44 weeks.

Among non-black patients, 40 percent achieved a sustained response to standard care. But as many as 68 percent of those also receiving boceprevir achieved sustained response at 28 weeks, the researchers found.

For black patients, the response rate was 23 percent for those receiving standard care and up to 53 percent with the addition of boceprevir.

The most severe side effect was anemia, which was seen in 13 percent of those receiving standard care and in 21 percent of those receiving all three drugs, Reddy's team noted.

In the other study, a group led by Dr. Bruce R. Bacon, director of the gastroenterology and hepatology division at St. Louis University Health Sciences Center, tested boceprevir on 403 patients with chronic hepatitis C. These patients had been previously treated with peginterferon and ribavirin.

Again, patients were divided into three groups similar to those in the other study. For those receiving boceprevir, the response rate was as high as 66 percent, compared with 21 percent for those receiving only peginterferon and ribavirin, the researchers found.

For patients who had no detectable hepatitis C RNA, the response rate to boceprevir was as high as 88 percent, the researchers noted.

As in the other study, anemia was the most serious side effect, affecting up to 46 percent of those taking boceprevir and 21 percent of those on standard care.

"The addition of boceprevir to peginterferon-ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV (hepatitis C) genotype 1 infection, as compared with peginterferon-ribavirin alone," the authors concluded.

Commenting on the studies, Dr. Donald M. Jensen, a professor of medicine at the University of Chicago Medical Center and author of an accompanying journal editorial, said "there is a significant improvement in sustained response [with boceprevir], which really relates to cure of hepatitis C."
Jensen noted that a similar drug is also being tested. "These drugs will offer patients a significant advantage over current therapy," Jensen said
Source

Boceprevir
VICTRELIS (boceprevir), Merck's investigational oral hepatitis C protease inhibitor, in combination with peginterferon alfa-2a and ribavirin.

A Better Way to Unbind Prometheus? Boceprevir for the Treatment of Chronic Hepatitis C Infection

Breaking Down Both Studies;

SPRINT-2
In the first trial, the SPRINT-2 Investigators enrolled 938 non-black and 159 black adult patients with previously untreated HCV genotype 1 infection (blacks and non-black cohorts were enrolled and analyzed separately as blacks are known to have a much lower response rate to standard therapy). After undergoing a 4-week lead-in with peginterferon alfa-2b plus ribavirin, patients were randomized to one of the following groups:

1) Peginterferon/ribavirin/placebo for 44 weeks (“standard therapy”)

2) Peginterferon/ribavirin/boceprevir for 24 weeks, with an additional 20 weeks of peginterferon/ribavirin/placebo if HCV RNA was detected between weeks 8 and 24 (“response-guided therapy”)

3) Peginterferon/ribavirin/boceprevir for 44 weeks (“48-week therapy”)

Results
SVR rates 24 weeks after completion of treatment were significantly higher in the boceprevir arms than in the standard therapy control group.

In an intent-to-treat analysis, 68% of non-black patients receiving fixed-duration triple therapy and 67% receiving response-guided therapy achieved SVR, compared with 40% in the control group.

Among black patients the corresponding SVR rates were 53%, 42%, and 23%, respectively.

Relapse rates in both fixed duration and response-guided boceprevir arms were significantly lower than in the standard-therapy control group.

Almost all boceprevir recipients with undetectable HCV RNA during weeks 8 through 24 went on to achieve SVR.

The most common treatment-related adverse events across arms were fatigue, headache, and nausea.
Anemia and dysgeusia (odd taste sensations) were significantly more common among boceprevir recipients.

Overall rates of discontinuation due to adverse events were similar across treatment arms. More people in the boceprevir arms, however, discontinued therapy (2% vs 1% in the control group), reduced drug doses (21% vs 13%), or used erythropoietin (43% vs 24%) due to anemia.

RESPOND-2
In the second trial, the HCV RESPOND-2 enrolled 403 subjects with HCV genotype 1 infection that had not responded to or had relapsed after prior treatment with standard peginterferon/ribavirin therapy.

Subjects were randomized to three arms very similar to those described for SPRINT-2:

Standard therapy, response-guided therapy (here after 32-weeks of triple therapy), or 48-week therapy. On the primary endpoint, subjects receiving boceprevir (i.e. those in the response-guided and 48-week therapy arms) again had significantly higher rates of SVR measured at 24 weeks after completion of therapy .

All participants initially received pegylated interferon/ribavirin for a 4-week lead-in period. They were randomly assigned to subsequently continue on pegylated interferon/ribavirin plus placebo for 44 more weeks or to add 800 mg 3-times-daily boceprevir.

Boceprevir recipients either stayed on triple therapy for 44 more weeks or used response-guided therapy. The latter group stopped boceprevir at week 36; those who had detectable HCV RNA at week 8 continued on pegylated interferon/ribavirin through week 48.

Results
In an intent-to-treat analysis, patients in the boceprevir arms again had significantly higher SVR rates -- 66% with fixed-duration therapy and 59% with response-guided therapy -- than those in the standard therapy control group (21%).

Among people with undetectable HCV RNA at week 8, SVR rates were 86% after 32 weeks and 88% after 44 weeks of triple therapy.

Among participants who had less than a 1 log IU/mL decrease in HCV RNA at week 4, one-third of boceprevir recipients still achieved SVR, compared with none in the control group.

Here too, the most common adverse events were fatigue, headache, and nausea. Anemia again occurred about twice as often in the boceprevir arms than in the control group.

"The addition of boceprevir to peginterferon/ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon/ribavirin alone," the investigators concluded, noting that fixed-duration and response-guided therapy were similarly effective.

Patients who previously relapsed after receiving standard therapy had SVR rates of up to 75% on boceprevir triple therapy, while previous non-responders had sustained response rates of 40% to 52%, they added in their discussion.

In summary, they wrote, the results of this trial "show that boceprevir, when added to peginterferon alfa-2b and ribavirin, leads to high rates of sustained virologic response in difficult-to-treat patients."

Results and Data Can Be Found At HIV and Hepatitis

Boceprevir; Four-Week Lead-In Response and IL28B Status Helped Define Likelihood of Achieving SVR

Boceprevir Helps Hepatitis C Patients with Cirrhosis
SUMMARY: Chronic hepatitis C patients with advanced liver fibrosis or cirrhosis were more likely to achieve a cure when they added boceprevir to standard therapy, according to a report this week at EASL 2011.

Slides;
Boceprevir in Addition to Standard of Care Enhanced SVR in Hepatitis C Virus Genotype-1 With Advanced Fibrosis/Cirrhosis: Subgroup Analysis of SPRINT-2 and RESPOND-2 Studies -


Boceprevir IL28B
IL28B genotype
In pre-specified analyses of the pivotal Phase III studies, researchers found that IL28B status (CC, CT or TT) was a strong baseline predictor of viral response at treatment week 4, week 8 and SVR among patients receiving boceprevir.iv Among those carrying the CC gene allele, 89 percent of treatment-naïve patients and 82 percent of treatment-failure patients had an early response, defined by undetectable virus (HCV-RNA) at treatment week 8, and were eligible for a shorter duration of therapy. Among those with the less favourable gene allele (CT or TT), 52 percent of treatment-naïve patients and 48 percent of treatment-failure patients had an early response and were eligible for a shorter duration of therapy.iv The analyses also showed that response after the 4-week lead-in was a stronger predictor of SVR than any single baseline variable, including IL28B status.iv The analyses included data from 63 percent of patients (912/1442) in the pivotal Phase III studies who received at least one dose of boceprevir or standard therapy and consented to genomic analysis to test for IL28B polymorphisms. In total, 28 percent of tested patients carried the CC allele, while 54 percent carried the CT allele and 18 percent carried TT.iv

Boceprevir Resistance
To better understand resistance-associated variants when VICTRELIS was added to standard therapy, researchers analyzed blood samples from 343 patients who did not achieve SVR in the HCV SPRINT-2 and HCV RESPOND-2 studies. Samples were obtained at various time points of virologic failure (breakthrough, incomplete virologic response, relapse and nonresponse), and resistance-associated variants were detected by population sequencing.

Results of this analysis [Oral presentation Parallel Session: HCV Therapy] showed that resistance-associated variants were highly associated with those patients not achieving SVR, and that the majority of patients with virologic breakthrough or incomplete virologic response had viruses with detectable resistance-associated variants.

When analyzed as a function of poor response after the 4-week lead-in (less than 1-log10 viral load decrease) versus good response (greater than or equal to 1-log10 viral load decrease), resistance-associated variants were more frequent in patients with a poor lead-in response (68 percent) compared with patients with a good lead-in response (31 percent). Additional analyses are ongoing, with a 3.5-year long-term follow-up study underway to evaluate the persistence of resistance-associated variants over time.


Slides:
BOCEPREVIR RESISTANCE-ASSOCIATED VARIANTS (RAVS) ARE OBSERVED MORE FREQUENTLY IN HCV (GT1)-INFECTED PATIENTS WITH POOR RESPONSE TO PEGINTERFERON ALFA-2B/RIBAVIRIN -

Of Interest;
From Bloomberg

The U.K.’s National Institute for Health and Clinical Excellence may restrict the new drugs to patients who have tried existing treatments without success, Thursz said. The agency may also require genetic tests to determine whether patients are likely to respond to the medicines, he said at the meeting of the European Association for the Study of the Liver.

Italy and Spain also may delay or restrict use, Craxi said. Italy spends about 350 million euros a year on existing hepatitis C treatments, he said. “If you triple the cost, that would be more than 1 billion euros,” he said.

Under Review The new drugs are being reviewed by regulators at the European Medicines Agency. Both are scheduled for U.S. Food and Drug Administration hearings at the end of this month.

In France, telaprevir and boceprevir received special temporary authorization in December, under a program designed for seriously ill patients for whom there is no other effective treatment on the market, according to French pharmaceutical regulator AFSSAPS. This allowed the drugs to bypass the usual approval procedures, the regulator said.

About 500 patients are being treated in France now, said Michel Bonjour, spokesman for SOS Hepatites. The new drugs are prescribed together with the current standard therapy of interferon and generic ribavirin, and the total cost of a yearlong cycle of treatment may reach 45,000 euros to 70,000 euros per patient, Bonjour said in an interview. The cost is covered in full by France’s national health insurance program.

‘Cost Effective’ “It’s not a good indication of price elsewhere,” Patrick Bergstedt, senior vice president for vaccines and infectious diseases at Whitehouse Station, New Jersey-based Merck, said in an interview.

The very sick patients in the French program get 44 weeks of treatment with boceprevir, while a more typical course of therapy is 24 weeks to 32 weeks, he said. There’s a “high likelihood” the eventual commercial price for a course of treatment will be less than the 30,000 euros Merck charges under the French program, he said.

“It’s black and white that these drugs are cost- effective,” Bergstedt said. “The challenge will be how do you stratify treatment, and how do you use these drugs responsibly to ensure the patients with the greatest need are treated first.”

12-Week Treatment Vertex, based in Cambridge, Massachusetts, referred questions to partner J&J, which will market telaprevir in Europe. J&J hasn’t decided on a final price, said Isabelle Lonjon-Domanec, global medical affairs leader for telaprevir at the New Brunswick, New Jersey-based company’s Tibotec Therapeutics unit.

Patients take telaprevir for 12 weeks together with standard treatment, then continue on the older standard drugs for a total of six months to a year of therapy.

Both new hepatitis C drugs are protease inhibitors crafted from the same technologies that led to discoveries in HIV research. Used in addition to existing therapies, they boost the chance of a cure from half of patients to between two-thirds and three-quarters of those treated, studies have shown.


In the U.S., the new drugs may be priced at $35,000 to $40,000, estimates Howard Liang, a Boston-based analyst at Leerink Swann & Co.

“A cure saves a lot of money down the road,” Liang said in an interview. “It’s a shock to physicians, but I think it can be justified because it’s a cure.”

Next Generation Hepatitis C, spread through contact with infected blood, is a virus that often lingers as a chronic condition, causing nausea and exhaustion as it destroys the liver over the course of years or decades. About 170 million people are infected, according to the World Health Organization.

Meanwhile, the next generation of drugs with even higher cure rates and fewer side effects is likely to reach the market within three years, Liang said.

Swedish drugmaker Medivir AB (MVIRB) has said it expects to begin selling a competitor pill to be used with interferon by 2013. Boehringer Ingelheim GmbH, Gilead Sciences Inc. (GILD) and Bristol- Myers Squibb Co. are among a dozen companies aiming for drug cocktails to replace the existing interferon combination.

Looming competition leaves Merck, Vertex and J&J without much time to recoup their investment, said Charles Gore, president of the Geneva-based patient advocacy group World Hepatitis Alliance.

“There is no easy answer to this,” Gore said in an interview. “We’ve got to have a way to give people access but incentivize the drug companies to research in this area.”

To contact the reporters on this story: Naomi Kresge in Berlin at nkresge@bloomberg.net; Carol Matlack in Paris at cmatlack@bloomberg.net