Alinia

[Andiamo1]

Romark Laboratories, a privately-owned biotechnology company, today announced results of a randomized phase II clinical trial showing that 79% of interferon-naïve patients with chronic hepatitis C genotype 4 receiving nitazoxanide plus the standard of care had a sustained virologic response (SVR), or undetectable level of virus, 12 weeks following treatment, compared to 43% of patients receiving the standard of care without nitazoxanide. The patients treated with nitazoxanide also experienced no relapse and no more side effects than patients who received the standard of care. Interim results from this Phase II clinical trial will be presented on Tuesday November 6 in an oral presentation at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.

"Patients treated with nitazoxanide responded earlier and maintained their responses without relapse after receiving only 36 weeks of treatment with peginterferon and ribavirin," said Dr. Emmet B. Keeffe, Chief of Hepatology at Stanford University School of Medicine. "These data suggest the emergence of a new therapeutic approach for treating hepatitis C. While more study is needed to confirm these results in a broader population of patients, nitazoxanide appears to increase the potency of interferon without increasing toxicity or inducing resistance."

Study Details
This Phase II randomized, controlled trial was conducted at two centers in Egypt and is part of the company's STEALTH C (Studies to Evaluate Alinia for Treatment of Hepatitis C) clinical development program, which is designed to evaluate the safety and efficacy of nitazoxanide tablets in combination with peginterferon or peginterferon and ribavirin (standard of care) in patients with chronic hepatitis C.

In the trial, 96 treatment-naive patients with chronic hepatitis C genotype 4 were randomized into three groups to receive either 48 weeks of standard of care treatment (n=40), 12 weeks of nitazoxanide followed by 36 weeks of nitazoxanide plus peginterferon (a dual regimen, n=28), or 12 weeks of nitazoxanide followed by 36 weeks of nitazoxanide plus standard of care treatment (a triple regimen, n=28). An additional 24 interferon-experienced patients were randomized to receive 12 weeks of nitazoxanide followed by either the dual regimen (n=12) or the triple regimen (n=12) for 36 weeks. Patients received 180 microgram injections of pegylated interferon (Pegasys®) once per week; nitazoxanide was administered as one 500 mg tablet twice daily; and ribavirin was administered as 1,000 or 1,200 mg daily according to weight.

Results
At 12 weeks following the end of treatment, naïve patients who received a triple regimen that included standard of care and nitazoxanide showed a significantly higher SVR (HCV RNA < 10 IU/mL, Abbott m2000) than the group receiving the standard of care regimen (79% vs. 43%, respectively) (p=0.006). The data also suggest a potential for eliminating or reducing the role of ribavirin in treating hepatitis C. Patients treated with a dual regimen of nitazoxanide and peginterferon showed an SVR at week 12 following the end of treatment that was not inferior to standard of care (68% vs. 43%, respectively) (+25%; 95% CI: -1%, +47%). Of 24 treatment-experienced patients, the triple regimen (n=12) resulted in an SVR of 25% at week 12 post- treatment, and the dual regimen group (n=12) had an SVR of 8%.

"Results from this trial validate a new approach to treating HCV that focuses on the interaction between the virus and the cell," said Jean-François Rossignol, M.D., Director of the Romark Institute for Medical Research. "With confirmation provided by this data we are aggressively pursuing development of nitazoxanide and related drugs to treat chronic hepatitis C and other viral diseases."

Nitazoxanide is the first of a new class of small molecule drugs called thiazolides that inhibit replication of a broad range of viruses. The drug was discovered by Dr. Rossignol and was initially developed by Romark and approved for marketing in the United States as the first treatment of cryptosporidiosis. Serendipitously, the development of nitazoxanide for treating cryptosporidiosis led to the discovery of its antiviral properties and ultimately to the discovery of a promising new class of antiviral drugs.

Romark is currently conducting a U.S. Phase II trial with nitazoxanide plus standard of care in patients with hepatitis C genotype 1 who were previously treated with interferon. The Company also plans to initiate a Phase II trial in treatment naïve patients early in 2008.

[Andiamo1]

Vertex stock is off 20% today.

[jmjm530]

Potentially very exciting! Thanks for posting. The riba aspect was also interesting.

Hope you're doing well,

-- Jim

[gauf]

I knew it! I knew it! I knew it!   SWEEEEEEEEEETTTT!!!!

[orleans]

Considering all the attention telapervir gets it sure seems like this post would be making a bigger splash than it is. Wasn't HR somehow involved or interested in Alina. I mean, 79% 12 week SVR w/ few if any additional sx seems like a HCV ROCK OUR WORLD kind of thing. Is this a "too good to be true " thing? I've been looking hard at the 950 phase 3 trial but MAN, this news kinda shakes that plan up. WHY was this thing done in Egypt and on g4s of all genos? I'm confused. jerry

[3txsofar]

Scratch the post before.

I have no bias towards or against Egypt, Arabs or Islam, but I have to raise a caution about drawing a lot of conclusions from an early phase study in Egypt.

I don't think the health system there is generally in a place to carry out rigorous trials, with strict attention to selection, blinding, maintenance of the blind, etc.

I doubt the FDA will put a lot of stock in it.  

Alinia could have value, but this info should to be discounted somewhat.

[willows]

I asked my doc a while ago about Alinia, he was less than enthusiastic because I am not geno 4.  Seems Egypt has a HUGE population of geno 4 and that genotype has some specifics about it that may not apply to the other genos.  This was just a brief conversation he and I had, so there is still much I do not know.

I do know that NOW that Vertex is about 18 months away from FDA approval, we have new drugs coming out of the woodwork.  And I am very very glad about it.  I am SO going to have a much better chance next time I tx than last time, the whole paradigm of SOC has changed like a m$$%$%# in only three years.  And what a great change it is.

I'm ready, bring it on.  Telaprevir, with a small side of Alinia and the new interferon that only needs to be injected bi-weekly.  Now if only we could get past the riba, I would not be dreading the tx again as much.  But I keep remembering how much it has all changed, we are finally catchin a break here!!

Willow

[merryBe]

same with my doc, not impressed, he's waiting for the conference....genos aside, there's also the gastro effects, which if you are already expanded liver/spleen wise don't make this an appealing addition as any gas with no room left means writhing in pain.......

although I'm gonna bring it up with him when he gets back from the conference and see if anybody changed his mind.

personally, after reading up on 12 new drugs and trials this year and hopefuls with serious sides I'm starting to get a little less eager about phase 1 and 2 for anything.....take a hundred people...what likelihood is there of seeing the breach births so to speak. I'm beginning to see why phase 3 is the real proving ground for most of these molecules. (considering probably dozens have come and gone because they failed in one way or the other)

plus, and same here, no prejudice, but what can pass the bar in Egypt where everyone isn't Sue HAppy....well, you just can't throw things out there in this country without the legals crying foul for every and anything...besides the FDA regulates studies, monitors bank accounts of researchers for payoffs etc........do they even have an FDA there???????

[orleans]

68% 12 week SVR w/ NO RIBA! Ya reckon a Dr would prescribe this stuff off label? Seems like you could start with all 3 drugs and if things started going "ribasouth" you could reduce or just drop the riba.  Isn't Procrit "off label" as far as HCV treatment is concerned. Wish I could find someone 'round here in a trailor to cook me up a batch, ahh, life in Alabama!! :) jerry

[moahunter]

If this is true, it would be fantastic. Riba is one nasty drug in my experience, it would be great to get rid of. I didn't mind interferon on its own, but once Riba was added to the mix, yuck.

[scratchinghead]

Hey merryBe! I don't pray, but I was praying that your doctor went to the conference in Boston. Looks like he did. I hope he took his cohort, Dr. Flora, with him. The Flora/Skinner team will be well informed and hopefully this will trickle down to our treatment(s), seeing as how my doctor is Dr. Flora. Maybe that is why I haven't heard back from him about my biopsy/blood test. He as busy packing for and flying to Boston.

[Forseegood]

told me he was off to the conference the other day...says he's very interested in speaking to the actual researchers, primary docs, from the various pharms, etc...says you can sometimes find out a lot more then what they put out in their abstracts and press releases...he knows a lot of those people personally since he's co-owned a biotech company himself...I'm really anxious to hear what he finds out about Alinia...

[merryBe]

yes so let's keep what info does come in up here, just in case they might start offering it. they often do reach new consensus at these things,
but whether it will be to put this into the mix or wait for state side research will be the question.

plus there's such a push for all the protease inhibitors it's really staring to look like the floor of wall street, everybody racing to get market share.
hmmmlet's see  treat 30 million times 60K that's about 2 billion in sales...and thats just in this country.....

[R Glass]

Man I hate reading threads like this. As “D Day” is soon approaching for me to start tx, this ads to my cold feet syndrome of, should I Treat or hold out.

[orleans]

I FEEL YA BROTHER!!!!:), Did some nitazoxanide pricing. In Canada the knock-off would cost < $6000 for a 48 week supply at 500mg twice daily. That is expensive, but if it works I'ld be willing to load up a couple of credit cards; would'nt yoi?? jerry

[orleans]

We're countin' on you for the "skinny" (I guess they use that saying way out there in the golden state:)!) Anybody know anything about geno 4? Is it more like 2&3 as far as treatability or more like g1? jerry

[Forseegood]

Kittyface (a member here) had gone on the Alinia herself, and got a 3 month supply. All she did was contact Romark and they were very nice about faxing (?) or sending her the forms, when she told them she didn't have the money for it. They sent her a 3 month supply within a week or so.

I feel kind of uncomfortable posting this on a public forum, but it's not like it hasn't been said before. I was probably too mouthy about HR and what he's doing, lol...you know how it is sometimes when you post late at night, not always the best judgment, particularly from me:)

Kitty said that her sides were negligible, but I think even with the trial people, some people did have stomach troubles, but I forgot all the particulars.

Just want to point out that no one is recommending a relatively untried treatment, but some of this info is promising, just don't know that much yet. Kitty took it as a stand alone treatment, and it didn't clear the virus for her.

It will be very interesting to see it tried out *with* soc with other genotypes, etc... Kitty is going to treat with soc and Alinia herself, I hope I'm not outing her, I think she already posted this, if not, I'm sure I'll be hearing from her if she's psst at my big mouth ha ha! It's good we're using screen names and not our own sometimes.

[Forseegood]

hate to say who told me this, but some people think that you wouldn't need to take alinia for your entire treatment time anyway, just the first 3 months or so (IF you were thinking about it and had a go from your personal doctor)...this is of course, just an estimation, in unknown waters....something I say with a lot of trepidation.

[orleans]

Wonder how tough it would be to get ones' Dr to go for the off label treatment?? jerry,Forsee, you don't really seem so "dizzy":)

[kittyface]

Re: wondering if doctors will write rx for Alinia, just ask for it, all they can say is no.  I'm lucky to have an open minded, progressive doc who is writing scripts based on my input.  I'm on the brink of starting tx and going with the trifecta:  Rebif (a peginteron beta-1a), ribavarin and Alinia.  

Rebif reportedly has fewer sx than regular peginterferon and is already approved for multiple sclerosis.  The downside is that I may not be able to get it "gratis" since it's not FDA approved for HCV.   If not, I'll go with SOC peg.  

FYI, for those of you who don't have insurance and can state a lower income, free drugs are available from the manufacturers and free lab testing is available from Quest Diagnostics.  Also, I think the larger drug stores have programs offering free or heavily discounted drugs to help with sx.  With a little homework and some paperwork you may be able to reach SVR without wiping out your life savings/investments.

Best to all,

Kittyface

[3txsofar]

Genotype 4 info -

Epidemiological Characteristics and Treatment Outcomes in Individuals with Genotype 4 HCV Infection

By Liz Highleyman

Research has shown that the natural history of hepatitis C virus (HCV) infection and response to interferon-based therapy are influenced by HCV genotype. Genotype 1 is more difficult to treat and is associated with lower sustained virological response (SVR) rates compared with genotypes 2 or 3.

There are less data -- some of it conflicting -- regarding genotype 4, which is being seen with increasing frequency in Europe (though still uncommon in the U.S.).

As reported in the July 2007 Journal of Viral Hepatitis, French researchers analyzed epidemiological features and SVR rates in a retrospective study of 1532 genotype 4 patients, including 1056 infected in France, 227 immigrants infected in Egypt, and 249 infected in sub-Saharan Africa.

SVR rates were assessed in 242 treatment-naive patients who received pegylated interferon plus ribavirin for 48 weeks.

Results

• HCV subtypes 4a or 4d were most common among patients infected in France, where the predominant route of transmission was injection drug use.

• Subtype 4a predominated (93%) among patients infected in Egypt, where transmission was mostly related to parenteral treatment for schistosomiasis.

• More than 7 different genotype 4 subtypes were found among patients infected in sub-Saharan Africa, a group with no apparent single predominant route of infection.

• Liver fibrosis was significantly less severe in genotype 4 patients infected in France or Africa compared with those infected in Egypt.

• However, SVR rates were higher in patients infected in Egypt, compared with those infected in France or Africa (54.9%, 40.3%, and 32.4%, respectively; P < 0.05).

• Overall, better treatment response was observed in patients infected with subtype 4a.

• In a multivariate analysis, the 2 factors independently associated with SVR were infection in Egypt and absence of severe fibrosis.

Conclusion

In conclusion, the authors wrote, "the distribution of HCV-4 subtypes varies with the geographical origin of transmission and affects the SVR following antiviral treatment."

07/10/07

Reference
D Roulot, V Bourcier, V Grando, and others. Epidemiological characteristics and response to peginterferon plus ribavirin treatment of hepatitis C virus genotype 4 infection. Journal of Viral Hepatitis 14(7): 460-467. July 2007.

[3txsofar]

I have some further Alinia observations, based on the above article and the original post in this thread.  The above article showed standard of care achieving SVR of 55% in Egyptian genotype 4 patients.  The control group in the the Alinia study only achieved 43%, which is a huge difference and would make me wonder about the integrity of the study.

The Alinia study reported 79% SVR at 12 weeks, which could decline as it reaches 24 weeks.  More importantly though you have to wonder how does 79% for Genotype 4 translate to SVR for genotype 1?  Certainly the success for geno 1 would be less, but how much?  On top of that, there is the questionable integrity of the study.

Personally, I have a lot of questions about the Alinia study.  Why did they go to Egypt, where standards for the trial are more lax?  Why Genotype 4, when every other major drug seems to start with 1?  Were they simply trying to get some headlines so they could get some off-label  use?

I would have much more confidence in a company that started trials in Europe or the USA with genotype 1 patients.  

This whole thing reminds me of leatrile clinics in Tijuana for cancer patients.

[gauf]

You are right to be skeptical. These results raise questions that need to be addressed, I am of the opinion that if it can't hurt to add it to SOC, then I want to add it. I am waiting with bated breath to see what HR has to report on it from the conference. Hope he posts as soon as he can.

[drofi]

and off-label money is money too. Some nice reports here and there work well.
We compare apples and pears by looking to different genotypes, patient populations, and conformity levels to GCP.

SVR-rate from SOC is 70% in Genotype 1, just creat a nice design:

Gastroenterol Clin Biol. 2007 Aug-Sep;31(8-9 Pt 3):20-8:
Larrey D, Couzigou P, Denis J.
The treatment of chronic hepatitis C, now well codified with the association of a pegylated interferon alpha and ribavirin, allows to obtain a prolonged virological response in more than half of the cases. The results are even better and reach about 70% of success when the treatment is optimized.

Nevertheless, I am excited to read the report about answers to critical questions from the Boston meeting.

Best regards, Drofi

[3txsofar]

The following was posted on yahoo finance -vertx by pinvestment

"it is amazing what people will latch on to

it will be interesting to see what VRTX has to say tonight as the street.com says it is holding an investor meeting tonight and will report additional data tomorrow morning
but one needs to consider that pegylated interferon alone can give a more than 80% SVR for type 4

so the new data that is considered to be so damaging for VRTX is actually for a genotype of HepC that is already very easy to treat with interferon alone

check it out for yourself

Pegylated interferon alpha-2b plus ribavirin in patients with genotype 4 chronic hepatitis C: The role of rapid and early virologic response.

Kamal SM, El Kamary SS, Shardell MD, Hashem M, Ahmed IN, Muhammadi M, Sayed K, Moustafa A, Hakem SA, Ibrahiem A, Moniem M, Mansour H, Abdelaziz M.
Department of Gastroenterology and Hepatology, Ain Shams University, Cairo, Egypt.
In patients chronically infected with hepatitis C virus (HCV) genotype 4, the optimum duration of therapy and the predictors of sustained virologic response (SVR) have not been adequately determined. In this study, 358 patients with chronic hepatitis C genotype 4 were randomly assigned to pegylated interferon (PEG-IFN) alpha-2b (1.5 mug/kg/week) plus oral ribavirin (10.6 mg/kg/day) for a fixed duration of 48 weeks (control group, n = 50) or for a variable duration (n = 318). In the variable-duration group, patients with undetectable HCV RNA at week 4 were treated for 24 weeks (group A, n = 69), patients with undetectable HCV RNA at week 12 were treated for 36 weeks (group B, n = 79), and the rest of the patients were treated for 48 weeks (group C, n = 160). The primary endpoint was SVR (undetectable HCV RNA 24 weeks after treatment cessation). Groups A-C and the control group had SVR rates of 86%, 76%, 56%, and 58%, respectively. After the study was controlled for predictors, a low baseline histologic grade and stage were associated with SVR (P < 0.029) in all groups. In addition, among patients in group C, older age (P = 0.04), a higher baseline body mass index (P = 0.013), and low baseline HCV RNA (P < 0.001) were also associated with SVR attainment. The incidence of adverse events and the rate of discontinuation were higher in patients in the variable-duration and fixed-duration groups treated for 48 weeks. Conclusion: In patients with chronic hepatitis C genotype 4 and undetectable HCV RNA at weeks 4 and 12, treatment with PEG-IFN alpha-2b and ribavirin for 24 weeks and 36 weeks, respectively, is sufficient. (HEPATOLOGY 2007.). "