Telaprevir Takes Center Stage as New HCV Approaches Advance

[StormRider]

http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bioWorldHeadlines_article&forceid=49174

AASLD Roundup


Telaprevir Takes Center Stage as New HCV Approaches Advance



By Trista Morrison



Staff Writer
As analysts predicted, the data coming out of embargo during the annual meeting of the American Association for the Study of Liver Disease (AASLD) don't appear to be triggering any major swings in biotech stock prices.

Yet the studies presented during the conference have provided details and answered outstanding questions about several emerging drugs for the treatment of hepatitis C virus (HCV). (See BioWorld Today, Oct. 17, 2008.)

The most-advanced alternative to the standard of care (ribavirin plus pegylated interferon) is Vertex Pharmaceuticals Inc.'s protease inhibitor telaprevir. Vertex's Chief Commercial Officer Kurt Graves told BioWorld Today that while the telaprevir data presented at last year's conference generated excitement about the drug's potential to increase responses and decrease treatment duration in treatment-naïve patients, this year's data have helped doctors appreciate the drug's potential in treatment-experienced patients.

While the treatment-experienced data were not new, Graves said Vertex provided additional details about its trials and patients, including characterization of patients as null responders, partial responders, relapsers or breakthroughs.

Interim data from PROVE3, an ongoing Phase IIb trial in treatment-experienced patients, showed that 52 percent of patients achieved a 12-week sustained viral response (SVR12), while only 30 percent of patients on the standard-of-care regimen had undetectable HCV RNA levels at the same time point.

Graves said additional relapses and discontinuations likely will drive the standard of care number down 10 percent to 12 percent overall, while null responders often have a zero to five percent chance of achieving an SVR when retreated with the standard of care.

Of the PROVE3 patients, SVR12 was achieved in 41 percent of null responders, 73 percent of relapsers and 44 percent of breakthroughs. Interim data from Study 107, an open-label Phase II follow-on to the PROVE studies, showed undetectable HCV RNA levels at week 24 in 43 percent of null responders, 82 percent of partial responders and 83 percent of relapsers - numbers that Graves called "unprecedented."

Cowen & Co. analyst Rachel McMinn wrote in a research note that the data continue to support telaprevir's activity "across the HCV treatment failure spectrum." Analysts are eagerly awaiting the SVR24 data from PROVE3, which Graves said will be available in late 2008 or early 2009.

Other telaprevir data to generate a buzz during AASLD came from Study 208, which compared twice-daily to three-times-daily dosing. While the three-times-daily regimen resulted in undetectable HCV RNA levels for 80 percent of patients at four weeks and 93 percent at 12 weeks, the twice-daily regimen held steady at 83 percent for both time points.

Analyst Howard Liang of Leerink Swann & Co. wrote in a research note that while the three-times-daily regimen appeared slightly better than the twice-daily regimen at 12 weeks, he suspects the differences are not meaningful and, since safety between the two groups was comparable, he believes that twice-daily dosing remains a "viable dosing option to explore."

Graves added that the four-week data are highly predictive of patients who will go on to achieve an SVR, while 12-week data are not. SVR24 data from Study 208 will be available next year.

Telaprevir's top competitor, boceprevir, a protease inhibitor from Schering-Plough Corp., also was the subject of a presentation at the AASLD conference. In a Phase II study, 74 percent of treatment-naïve HCV patients achieved an SVR12, and 56 percent achieved an SVR24 on a boceprevir-plus-standard-of-care regimen, compared to a 38 percent SVR12 for standard-of-care alone.

Susquehanna Financial Group analyst Jason Kolbert wrote in a research note that the "critical difference in Vertex's favor" remains boceprevir's poor performance in treatment-experienced patients, although he noted the performance is "hard to understand" and the trial may have been flawed.

Both telaprevir and boceprevir are being studied in Phase III trials in treatment-naïve and treatment-experienced HCV patients.

Graves added that the future of HCV treatment may one day allow patients to avoid treatment with interferon and perhaps ribavirin by combining protease inhibitors like telaprevir with other targeted antivirals, such as polymerase inhibitors.

He predicted that "this kind of development work will get under way" next year.

Pharmasset Inc. had several presentations with its polymerase inhibitors R7128 at AASLD, but analysts seemed most interested in discussions of monkey toxicity issues that took place during the company's investor event.

Liang wrote that a "no adverse effect level" (NOAEL) was established, and while the company's refusal to reveal the dose may have created some skepticism, the worst-case scenario would have been if the NOAEL could not be established.

Kolbert added that the toxicity appears "reversible and dose dependent and likely monitorable by standard lab assays."

Another new HCV approach highlighted at AASLD was GlobeImmune Inc.'s immunotherapy GI-5005. The drug combines HCV antigens with a yeast-based delivery system, and initial Phase II data demonstrated a 2.6-fold improvement in rapid viral response at four weeks in treatment-naïve HCV patients with high viral loads at baseline who received GI-5005 plus standard of care, compared to standard of care alone.

In other AASLD news:

• Anadys Pharmaceuticals Inc., of San Diego, presented Phase I data showing that its non-nucleoside polymerase inhibitor ANA598 was well tolerated with no serious adverse events and demonstrated a pharmacokinetic profile consistent with once-daily or twice-daily oral dosing for HCV. A Phase Ib study is under way, as is a separate Phase Ib HCV study with the oral, Toll-like receptor 7 agonist prodrug ANA773.

• Gilead Sciences Inc., of Foster City, Calif., presented two-year data from Study 102 and Study 103, its ongoing, eight-year pivotal Phase III trials of Viread (tenofovir disoproxil fumarate) in hepatitis B. After 48 weeks of treatment with Viread or Gilead's Hepsera (adefovir dipivoxil), all patients in both trials were rolled over onto Viread monotherapy. The two-year data showed continued viral suppression and no development of mutations associated with resistance. Viread, which has been approved for HIV since 2001, gained approval in HBV this year. (See BioWorld Today, Aug. 13, 2008.)

• Romark Laboratories LC, of Tampa, Fla., presented data from a Phase II trial using the thiazolide nitazoxanide to pretreat HCV patients prior to adding interferon. Of patients pretreated for four weeks, 80 percent experienced a 24-week sustained viral response (SVR24), while 61 percent of patients pretreated for 12 weeks achieved an SVR24. There were no serious adverse events. The company said the data indicated potential for a shorter pretreatment period and elimination of ribavirin.

• Tibotec BVBA, a unit of New Brunswick, N.J.-based Johnson & Johnson, presented interim data from a Phase IIa HCV trial of protease inhibitor TMC435. The data demonstrated that 89 percent of patients treated with the highest dose of TMC435 combined with standard of care achieved undetectable HCV RNA levels at four weeks. Additionally, patients receiving TMC435 as monotherapy for the first seven days achieved mean HCV RNA reductions of 2.63 log10 IU/mL at the 25-mg dose and 3.43 log10 IU/mL at the 75-mg dose, compared to 3.47 log10 IU/mL and 4.55 log10 IU/mL when each dose was combined with standard of care. There were no serious adverse events.



Published  November 4, 2008

[lapis]

Thank you for this post.  Hadn't seen this article yet, and it is such good news.  I'm in 4th week of tx in a trial, and feeling very very hopeful.

[foofighter]

Awesome news. We'll be watching for your posts. Good luck!

[StormRider]

Just learned today that I will be starting SPRINT-2 : ) this Friday 11/07. Will keep you all posted.

[VXman]

The article written by Trista Morrison although thorough and detailed failed to mention that Vertex stock was at $18.83 on October 28 and is now $28.54. That is a 51.6% increase in less than a week. It had everything to do with the lead up to the AASLD meeting and the positive news portrayed in the abstracts. Her opening statement, "don't appear to be triggering any major swings in biotech stock prices", certainly doesn't apply to Vertex. I would argue that this was a significant swing, and I hope it continues to rise in value. The Prove 3 trial was very good to me and the public is beginning to realize the real value of telaprevir.

[foofighter]

Nov. 20 for me and Fret is the 13th I believe. I think Virgocharm in the next couple weeks also in SPRINT-2 (liked learning the fancy-schmancy trial names in Boceprevir post that you put up).

And Rocker (as you mentioned) in RESPOND-2 and maybe can-do and the Bills.  We should have a fair number of people posting. I am heading off to Las Vegas with the over-70 set (my folks) next week and then I will be ready to rumble.

Any opinions out there on using the health tracker feature... helpful or too much work?

[StormRider]

Hi Foo... Hope all is well with you, haven't talked in awhile. Are you still starting around the end of November? Looks like I will be starting around that time also. This was some interesting info, my hep Doc is pretty excited about the new drugs coming out, he says they are progressing quickly. Take care...

[comeagain]

Yes very interesting have to save it and read it through again.
bajawoman I don´t think it says the meds are gonna be available next year

"He predicted that "this kind of development work will get under way" next year."
This is about testing different new meds together without interferon and riba i think.

ca

ps thx for posting rider well done

[bajawoman]

Thanks for the post this is one I missed it is good news all around and the new treatments as I read it will be available next year? That is wonderful news  Thanks again
gives me HOPE
Sidne

[PegOnPeg]

Thanks for this...I was hoping someone would filter thru & post.  This is all very promising news...I wish I could afford to wait longer...I'd chase down any one of these trials.

Alas...

Peg

[Isobella]

Thanks for posting....I am going to see my trial nurse in the morning.  I may have the chance to out "scoop" her, LOL!

[foofighter]

Thanks for posting the content. I haven't had the energy to dig through all the topics that Jim posted to even begin. This info is of particular interest to me at this moment (would imagine to others that are in "trial mode" as well) so I was happy to have it right there in front of my face.

[StormRider]

My first posting of a news article, would like to hear your comments.