Albuferon No Better than Pegasys -- Trial Report

[jmjm530]

BANGALORE (Reuters) - Human Genome Sciences' (HGSI.O) drug to treat chronic hepatitis C met the main goal in a late-stage trial, but failed to show numerically better efficacy compared to standard-of-care, raising questions about the drug's adoption and sending shares crashing to an all-time low.

Analysts had expected the trial to meet its main goal of non-inferiority compared to Pegasys, but they had also said that the trial must show numerically better sustained virologic response (SVR) rates to convince the market of the drug's commercial viability.

In the trial, named ACHIEVE 1, patients were either given the drug Albuferon every two weeks or standard-of-care Pegasys once weekly and the company said the rate of SVR among the two groups "was comparable."

"This means that you have a drug that is statistically comparable but for the vast majority of prescribers who have used Pegasys for ever, they are not going to change their prescribing trends based on this data," said Piper Jaffray analyst Edward Tenthoff.

The current standard of care for hepatitis C is antiviral ribavirin in combination with an interferon. Human Genome's Albuferon, which is a type of interferon, was also being studied in combination with ribavirin.

Interferons currently in the market are Roche's (ROG.VX) Pegasys and Schering-Plough Corp's (SGP.N) PegIntron. Interferon treatment is hard to tolerate and can cause flu-like symptoms.

Patients on the arm receiving 900 micrograms of albuferon had SVR rates of 48.2 percent, while patients on the Pegasys arm achieved SVR rates of 51.0 percent.

Patients originally randomized to receive 1,200 micrograms of albuferon had SVR rates of 47.3 percent.

"SVR rate is the key prescribing criteria (for physicians). With a numerically inferior SVR rate, Albuferon will have difficulty unseating market leader Pegasys," said Tenthoff, who downgraded the stock to "neutral."

Albuferon's sole benefit is less frequent dosing but the trial did not show the quality of life benefits observed in prior studies, Tenthoff said and cut his price target on the stock to $1.70 from $6.

Higher rate of pulmonary adverse events and discontinuations in the albuferon arm may limit its ability to take market share from Pegasys, said Leerink Swann's Joseph Schwartz.

The company also has $404 million in convertible debt due in 2011 and 2012.

"We project Human Genome has sufficient cash to reach Albuferon approval next year. However, we believe the debt will remain an overhang and negatively impacts our cash flow projection," Piper's Tenthoff added.

Human Genome is developing Albuferon in partnership with Swiss drugmaker Novartis (NOVN.VX) under an agreement signed in June 2006.

The company expects to file for marketing approvals globally in the fall of 2009.

Shares of Human Genome, which touched an all-time low of 80 cents, recovered some losses to trade at 95 cents in midday trade on Nasdaq.

http://www.reuters.com/article/hotStocksNews/idUSTRE52854X20090309

[desrt]

See:
http://www.medhelp.org/posts/show/287389

Also:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17355620

[nygirl7]

It makes absolutely no sense to me but either way I would not want to be in that trial.

[portann]

http://en.wikipedia.org/wiki/Hepatitis_C_virus:

"Infection with one genotype does not confer immunity against others, and concurrent infection with two strains is possible. In most of these cases, one of the strains removes the other from the host in a short time[7]. This finding opens the door to replace strains non-responsive to medication with others easier to treat."

The above is a discussion of different genotypes, not subtypes of one genotype.

[Willy50]

I have to wonder what would have happened if they had added 3 more albuferon arms in their last trial

1 arm with a 10% higher dosing for 12 weeks

1 arm in which it was weight based (they would concoct a formal)

1 last arm with some other permutation of tweaking a treatment.  (RBV lead in, 4 weeks double dosing; something)

Had they been able to have shown some area in which their drug could be used and was superior, even where it was not apples to apples comparison I'd guess that their stock price might look differently today.  Even if it were inferior the idea would be to mask it.  Frankly; if it is inferior it does not appear to be by much.  Different trial may equal different and superior results.  My point is that they should have been able to somewhat mask that with a few other arms and still claim "superiority".  If the drug was used in a slight variation of TX and proved superior that would be true.

What if they had compared it to Peg-Intron instead of Pegasys?

For me it still looks virtually equivalent.  It could become a immediate generic version and still get market share and still have value.

Looks to me that they went down to the line with no "Plan B".

best,
Willy

[nygirl7]

"Can a G-1 who has SVR'd also be infected de nouveau with G-1?"

Of course you can there is no immunity to HCV whatsoever.

I've never ever heard of anybody infecting themselves with a different geno to get rid of the tougher geno - that makes no sense You would just end up with two separate geno's.

I had two geno 1's - it didn't wipe out the other and neither would infecting myself with a geno2........it'd just be more virus typing.

[Max60]

Having three drugs that basically do the same thing might turn out to be good for health care consumers. In the future price may well become a factor. If insurance companies had a choice between say half a dozen drugs whose efficacy was almost identical, perhaps big pharma would have to revisit pricing policies.

Seems like they may see that coming what with the spate of mergers we're seeing.

A concern hardly ever mentioned on any board is producing a tx that can be made available to everyone. . . not just the diminishing number who have unlimited insurance dollars to spend.  

[jmjm530]

To Jim: For the same reason that peg was considered an 'advance' over non-peg:  bi-weekly injections compared to weekly or thrice weekly. Is that irrelevant to patients?
-----------
That was the hope, that Albuferon would help with QOL on treatment but the study showed it didn't.

PA:I understand that a G-1 who has SVR'd can be infected with G-2, 3, 4, 5 or 6. Can a G-1 who has SVR'd also be infected de nouveau with G-1?
------------------------------------------------------------------------
Yes. No immunity as far as I know, regardless of genotype.

[jmjm530]

Thank's for clarifiying. I thought you were arguing the opposite, but now I see. That said, if Albuferon demonstrated signficantly less sfx (it doesn't) then the 3% as I understand it may not be a reason to choose Pegasys since if the difference isn't statistically meaningful. What I think that means if they ran the whole thing over again, it very could have well come out the other way as the stats were so close.

[portann]

To Jim: For the same reason that peg was considered an 'advance' over non-peg:  bi-weekly injections compared to weekly or thrice weekly. Is that irrelevant to patients?

Call that a superior SVR rate for Pegasys if you want. I'd say it's not significant and the results are so close it could come out the opposite in another study.

--------------------------------------------------------------------------------------------------------------------

Jim and FlGuy, have you heard some wild idea that if G- 1's were deliberately infected with G-2, G-2 would destroy G-1. Then as a G-2, you'd have better tx chances and shorter tx time. Is that a lunatic theory, like blue algae?

I understand that a G-1 who has SVR'd can be infected with G-2, 3, 4, 5 or 6. Can a G-1 who has SVR'd also be infected de nouveau with G-1?

[FlGuy]

The point I was trying to make is that if effectivness is equal, opt for the less frequent. With Peg about 3% more that Albuferon, it's a clear distinction in Peg's favor.  IF they were equal in effectiveness Peg would still allow for more stylizing.

[jmjm530]

(if not statistically signficantly higher) should have read ("but not statistically significant")

[jmjm530]

FL: Tell that to the 6 of 100 who otherwise would have been svr...In another thread Bill and Portann point out that even if equal results, an advance is an advance even if it's less frequent dosing.  And I agree
---------------------------

Maybe I'm not interpreting you comment (or the study) correctly, but my read is that Pegasys delivers a superior (if not statistically signficantly higher) SVR rate. Also, that no QOL benefits are seen from the less frequent dosing of Albuferon. Based on this, why would anyone want to treat with Albuferon versus Pegasys? I do't see the "advance" you appear to suggest.

-- Jim

[nygirl7]

That's too bad, another one bites the dust ah........how many have we thought were promising but just came and went.  Hopefully this new government will help get some more things going....how disappointing.

"Interferon treatment is hard to tolerate and can cause flu-like symptoms. "


That always makes me crack up talk about an understatement ;)

[FlGuy]

"This means that you have a drug that is statistically comparable but for the vast majority of prescribers who have used Pegasys for ever, they are not going to change their prescribing trends based on this data,"

Tell that to the 6 of 100 who otherwise would have been svr.

In another thread Bill and Portann point out that even if equal results, an advance is an advance even if it's less frequent dosing.  And I agree.  I could also understand how Albuferon may be a little more difficult to modulate, than Pegasys/PegIntron, if the treatment regimen called for Peg 'stylizing'  like more frequent dosing or upping the dosing.