Replies to post #131802 on Biotech Values

[DewDiligence]

GILD/VRUS/IDIX/INHX/JNJ/BMY/Roche/etc—Ah ok, I think I follow you. In effect, JNJ/Medivir doesn't necessarily need a formal partnership deal for PSI-7977 or any other nuke. Provided TMC435 and 7977 make it to market, even in the absence of the FDA formally approving the combo, it's likely doctors will prescribe the drugs in combo anyways.

Right. The notion that other HCV companies must compete directly with GILD by developing an in-house all-oral regimen is based on a false premise, IMO.

If PSI-7977 is the best nuke (as it currently appears to be), why should JNJ and BMY try to force the pairing of a good PI or NS5A inhibitor with a second-rate nuke? It may make more sense for these companies to bring their PI and NS5A drugs to market on their own and let them gain commercial traction from combination with PSI-7977. In the HIV arena, this is how such drugs as Reyataz and Sustiva (prior to inclusion in Atripla) became big sellers.

When viewed in the above light, it’s easier to understand the colossal price GILD is paying to acquire VRUS.

[DewDiligence]

BMY/JNJ plan phase-2 trial of BMS-790052+TMC435 in genotype-1 patients:

http://finance.yahoo.com/news/Bristol-Myers-Squibb-Enters-bw-4207325656.html?x=0

…the companies will evaluate the potential to achieve sustained viral response 12 and 24 weeks post treatment in patients with HCV genotype 1 in a study with three treatment regimens: an oral, once-daily treatment regimen of daclatasvir and TMC435 with pegylated-interferon alpha plus ribavirin; an oral, once-daily treatment regimen of daclatasvir and TMC435 with ribavirin [i.e. no ifn] and an oral, once-daily treatment regimen of daclatasvir and TMC435 alone. The study is planned to start in the first half of 2012.

This trial is plainly intended to give BMY and JNJ an avenue for testing an all-oral HCV combination that does not include PSI-7977 and thereby does not rely on GILD. If the results of the trial are positive, BMY and JNJ could then ink a full-fledged collaboration to bring such a combination to market.

BMS-790052 (a/k/a daclatasvir) from BMY is the leading NS5A inhibitor; TMC435 from JNJ/Medivir is the leading second-generation PI. In previously announced phase-2 trials, each of these dugs is being tested in combination with PSI-7977.

[kamehameha]

Provided TMC435 and 7977 make it to market, even in the absence of the FDA formally approving the combo and in the absence of any formal deal between the two companies, it's likely doctors will prescribe the drugs in combo anyways.

most doctors know about the experiences with nucs in Chronic Hepatitis B

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861763/

and will want to rely on test results, rather than risking law suits.

"The side effect profile for the five approved agents was generally good during registration trials, but there have been reports of serious adverse events including myopathy, neuropathy, pancreatitis and renal impairment during post marketing surveillance."

"The five approved oral agents for CHB are analogues of nucleosides or nucleotides that pharmacologically inhibit the HBV polymerase in order to decrease viral replication and serum HBV DNA levels. ... All five approved agents carry a US Food and Drug Administration black box warning of potential mitochondrial toxicity "

"Another important consideration is lactic acidosis, for which all five approved oral agents carry a black box warning."

[rkrw]

You need to consider "cost to cure." Insurers may have something else in mind.

Provided TMC435 and 7977 make it to market, even in the absence of the FDA formally approving the combo and in the absence of any formal deal between the two companies, it's likely doctors will prescribe the drugs in combo anyways.