I see that R7128 has apparently shown kidney tox in monkeys. That has to be a bit of a concern for this drug to say the least, isn't it? I would imagine the FDA would require a lot of safety data to prove this doesn't occur in humans. Is it known yet if this just occurs at a much greater dose than what is being utilized in human trials?
This would be very big news if the algorithm really worked, but my guess is that it’s yet another case of finding an association that has no prognostic value.
The general principle (which is highly relevant to biotech investing): If you look at a data set determined to find some kind of association, it is almost a certainty that you will.
CHICAGO, Dec 22 (Reuters) - Doctors hope to be able to better predict which patients will respond to traditional treatment for the hepatitis C virus using a new method for identifying slight variances in the virus' genetic makeup.
U.S. researchers said on Monday that the technique may prove useful for other viruses such as HIV as well. The finding could be used to develop a test that would analyze a patient's specific virus strain before treatment was started.
A team at Saint Louis University in Missouri analyzed genetic patterns of the virus in patients infected with Hepatitis C to see if they could tell why many patients fail to respond to standard treatment with pegylated-interferon and ribavirin.
The year-long therapy activates the body's natural defenses against viruses, but patients often feel as though they have a bad case of influenza. Only about half of the people who suffer through the treatment actually respond.
"This is a very difficult therapy to take. It's really hard on the patient," said John Tavis, a professor of molecular and microbiology at Saint Louis University, whose study appears in the Journal of Clinical Investigation.
"If you can identify those patients who aren't going to respond anyways because they've got a strain that is highly resistant to the drug, then you just don't treat those patients and you save them $20,000 to $30,000 in medical bills just from drugs alone -- not to mention the side effects," Tavis said in a telephone interview.
He and colleagues studied the ribonucleic acid or RNA chains of the hepatitis C virus, looking for patterns that would explain why some people responded to the treatment while others did not.
Using a math formula, they zeroed in on a specific pattern of changes called "covariance networks" that differed depending on whether the drug worked. And these patterns proved to be a strong indicator of whether the virus was especially resistant to therapy.
"What we found will allow a doctor to predict whether or not a medication will work in a patient," Tavis said in a statement.
The finding also may have implications for other types of RNA viruses, such as human immunodeficiency virus or HIV or the influenza virus.
"It's a pretty easy process. The algorithm can be applied fairly quickly," he said. Whether or not it turns up a pattern that will be useful is less clear, he said.‹
The following paragraphs are in descending order of likelihood of success. (There is no claim of completeness here; i.e. paragraphs 3-6 do not necessarily mention all of the applicable drug candidates within the grouping.)
1. The two leading protease inhibitors: Telaprevir (VRTX/JNJ; phase-3) and Boceprevir (SGP; phase-3). The Telaprevir program is further advanced, so let’s call Telaprevir and Boceprevir 1a and 1b, respectively.
These two drugs have shown comparable efficacy in 24-28 week regimens of phase-2 trials in the genotype-1, treatment-naïve setting: #msg-31190433, #msg-33793333, #msg-33282976. Background posts: VRTX PROVE-1/2 trials made simple: #msg-29019931; PROVE-1/2 detailed results: #msg-28746843; overview of Telaprevir phase-3 program: #msg-26228377; Boceprevir starts phase-3: #msg-29474929.
Telaprevir and Boceprevir are also being tested in the second-line setting, Telaprevir in 24- and 48-week regimens and Boceprevir in 36- and 48-week regimens. Background posts: Telaprevir phase-3 REALIZE study: #msg-32901932; Telaprevir phase-2b PROVE-3 study: #msg-29896176; Telaprevir ‘107’ open-label phase-2 extension for PROVE-1/2 failures: #msg-33282976; Boceprevir phase-3 RESPOND-2 study: #msg-29474929.
2. ITMN-191 and R7128, the two oral drugs that Roche is testing is the INFORM-1 study that does not include interferon or ribavirin: #msg-33967428, #msg-33446127, #msg-33497987. ITMN-191 a.k.a. R7227 (ITMN/Roche; phase 1b) is a protease inhibitor: #msg-28126092. R7128 (VRUS/Roche; phase-1b) is a nucleoside polymerase inhibitor: #msg-33300630 (kidney tox in monkeys), #msg-32238916, #msg-32651030.
Although ITMN-191 and R7128 are not necessarily the best drugs in their respective classes, the fact that Roche is testing them in INFORM-1 gives them a leg up on competing drugs at the same stage of development, IMO.
3. Agents in phase-2b or phase-3 that use an established MoA: Albuferon (HGSI/NVS; phase-3), an albumin-conjugated interferon : #msg-34043876, #msg-34071611, #msg-13781766, #msg-20275478; BI201335 (B-I; phase-2b), a protease inhibitor: #msg-33564560; and Locteron (Biolex; phase-2), a long-acting interferon made in transgenic plants that may qualify for the 505b2 approval pathway: #msg-28786162. (Biolex recently bought out its partner, OctoPlus, and raised $60M to fund the Locteron program: #msg-32662307, #msg-32662762.)
4. Agents in phase-1b or phase-2 that use an established MoA. These include TMC435 (Medivir/JNJ; phase-2), a protease inhibitor: #msg-33283588;; MK-7009 (MRK, phase-2a), a protease inhibitor: #msg-34337398, #msg-34335327; SCH 900518 (SGP, phase-2a), a protease inhibitor (SGP’s follow-up to Boceprevir): #msg-34338549; GS-9190 (GILD; phase-2 starting by year-end), a non-nucleoside polymerase inhibitor: #msg-32919311; ANA598 (ANDS, phase-1b), a non-nucleoside polymerase inhibitor: #msg-34678306; IFN-alpha-XL (FLML; phase-1b): #msg-28837983; and IFN-Lambda (ZGEN; phase-1b): #msg-33311734.
5. Very-early-stage compounds that use an established MoA. These include IDX184 (IDIX; phase-1), a nucleotide polymerase inhibitor: #msg-31043481, #msg-26915921; and ACH-1625 (ACHN; preclinical), a protease inhibitor: #msg-31459921; IDX375 (IDIX, preclinical), a non-nucleoside polymerase inhibitor: #msg-34334563, #msg-31043481; and IDX136/IDX316 (IDIX, preclinical), two related macrocyclic protease inhibitors of which IDIX will select one to advance into phase-1: #msg-31043481.
6. Early- and very-early-stage compounds that use a novel MoA. These include BMS-790052 (BMY, phase-1), an NS5A inhibitor: #msg-33270670; A-831 (AZN, status unknown), an NS5A inhibitor: #msg-16682361; a preclinical NS5A program that GSK acquired from GNLB: #msg-33209281, #msg-33211420; ANA773 (ANDS, phase-1), an oral TLR7 modulator: #msg-33244419; IL-7 (Cytheris, phase-1/2) an injectable immunomodulator: #msg-33152073; GI-5005 (GlobeImmune, phase-2), an injectable immunomodulator: #msg-33322543; ACH-1095 (ACHN/GILD; preclinical), an NS4A inhibitor: #msg-31459921; an unnamed NS5A inhibitor from Presidio Pharma (status unknown): #msg-27791536; and clemizole (Stanford University; preclinical), an NS4B inhibitor: #msg-31857987.
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