Replies to post #115940 on Biotech Values

[DewDiligence]

Boceprevir’s proposed brand name is…(drum roll)…Victrelis!

http://finance.yahoo.com/news/Merck-Announces-New-Data-bw-222783952.html?x=0&.v=2

The name sounds like what you would get if you spilled your Vitalis hair tonic on your RCA Victrola.

[DewDiligence]

China’s HCV market will attain sales of $250M in 2015, according to Decision Resources:

http://finance.yahoo.com/news/Chinas-Hepatitis-C-Virus-bw-3356544922.html?x=0&.v=1

Peg-IFN-alpha agents have been included in the 2009 National Reimbursement Drug List in China, with a reimbursement rate that ranges from 50 to 90 percent and varies by region.

[DewDiligence]

NVS’ Lescol Improved SVR Rate When Added to SoC

[This result is more of a curiosity than a serious solution to treating HCV, IMHO. Lescol (fluvastatin) is an also-ran statin from NVS that was approved in the mid 1990s.]

http://www.bloomberg.com/news/2011-03-31/cholesterol-drug-improved-hepatitis-c-patient-response-in-study.html

›By Naomi Kresge - Mar 31, 2011

Adding a cheap cholesterol drug to the standard therapy for hepatitis C helped more patients clear the virus from their bodies in a study.

About 63 percent of those who took the generic medicine fluvastatin with the standard treatment were virus-free, compared with about half of patients who took the standard therapy of interferon paired with ribavirin alone, investigators said today at the European Association for the Study of the Liver conference in Berlin. The study followed 209 patients for 72 weeks of treatment [i.e. 48 weeks of treatment and 24 weeks of post-treatment observation].

Fluvastatin is part of a class of drugs known as statins, which doctors prescribe to patients who are at risk of developing heart disease. Statins reduce the liver’s ability to make cholesterol, which can build up in blood vessels and lead to heart attacks. The same signs that lead doctors to prescribe statins, such as excess weight, also leave hepatitis C patients at higher risk of complications, said Heiner Wedemeyer, the secretary-general of EASL, in a statement.

“It’s quite nice to see a study that doesn’t use something outrageously expensive,” Mark Thursz, a professor of hepatology at Imperial College London, said in a press conference today.

Two new hepatitis C drugs that may be introduced this year were more effective than the fluvastatin combination in studies. They are telaprevir, from Cambridge, Massachusetts-based Vertex Pharmaceuticals Inc. (VRTX) and New Brunswick, New Jersey-based Johnson & Johnson (JNJ), and boceprevir, from Whitehouse Station, New Jersey- based Merck & Co. Both are used with older medicines interferon and ribavirin.

Earlier Study

Fluvastatin is sold under the brand name Lescol by Basel, Switzerland-based Novartis AG. Lescol had sales of $436 million last year. A 31-patient study in 2008 found that fluvastatin had a modest and short-lived effect against hepatitis C, the researchers said.

The results of today’s study are “very exciting for clinicians,” Wedemeyer said.‹

[DewDiligence]

HCV: Most Likely to Succeed (IMHO)

[Updates:
EASL presentations from various companies;
my own musings that Telaprevir will outsell Boceprevir by about 4:1.]


The following paragraphs are in descending order of likelihood of success. There is no claim of completeness in this compilation, i.e. paragraphs 2-6 do not necessarily mention all of the applicable drug candidates within a given grouping.

Please see #msg-49115388 for the distinction between a nucleoside and a nucleotide; also see #msg-43114117 for historical perspective from the HIV arena.


1. The two leading protease inhibitors: Telaprevir (VRTX/JNJ; NDA submitted) and Boceprevir (MRK; NDA submitted). Between these two, I consider Telaprevir the favorite. The table in #msg-54317080 compares Telaprevir’s and Boceprevir’s phase-3 results in the first- and second-line settings. Although this comparison is somewhat unscientific, it suggests that Telaprevir is the drug to beat.

It’s important to recognize that MRK has used a non-standard (and IMO disingenuous) definition of what constitutes a null responder to SoC therapy, and any comparison of Telaprevir and Boceprevir in the second-line setting must take this into account (#msg-54316658, #msg-54376207).

All told, I expect Telaprevir to outsell Boceprevir by about 4:1 (#msg-61543324), , assuming both are approved in the same jurisdictions.

Telaprevir in the first-line setting: #msg-50595952 (results of phase-3 ADVANCE study—PR); #msg-50595752 (results of ADVANCE study—data table); #msg-53150647 (results of ILLUMINATE study); #msg-56129295 (% of patients in ADVANCE & ILLUMINATE who stopped treatment at 24w); #msg-53158692 (explanation for higher SVR rate in 24w arm of ILLUMINATE); #msg-61716397 (IL28B variants in ADVANCE); #msg-55917427 (phase-3b study of TID vs BID dosing); #msg-43114192 (‘C208’ phase-2 study of BID vs TID dosing); #msg-60417743 (phase-2 data in HCV/HIV co-infection).

Telaprevir in the second-line setting: #msg-54315761, #msg-54152015 (REALIZE data); #msg-61716397 (IL28B variants in REALIZE).

Boceprevir in the first-line setting: #msg-52949888, #msg-61543371 (SPRINT-2 data); #msg-56129390 (duration of treatment in SPRINT-2); #msg-61718223 (IL28B variants in SPRINT-2); #msg-52963584, #msg-37298085, #msg-50187183 (questions about anemia and EPO use).

Boceprevir in the second-line setting: #msg-54316658, #msg-54376207 (exclusion of null responders from RESPOND-2); #msg-52949888, #msg-61543324 (RESPOND-2 data); #msg-56129390 (duration of treatment in RESPOND-2); #msg-61718223 (IL28B variants in RESPOND-2); #msg-52963584, #msg-37298085, #msg-50187183 (questions about anemia and EPO use).


2. Other programs in phase-2b or later: ANA598 (ANDS; phase-2b), a non-nucleoside “palm” polymerase inhibitor: #msg-58413513 (phase-2b design), #msg-52795076 (interim SVR12 data from phase-2a), #msg-50475044 (12-week phase-2a data), #msg-50504158 (phase-2a EVR table and questions about non-ITT reporting), #msg-50475368 (bearish assessment), #msg-40064675 (musings on phase-1b data); BI 201335 (Boehringer Ingelheim; phase-3), a protease inhibitor: #msg-61666265 (phase-3 program), #msg-61754832, #msg-61682791 (phase-2b data), #msg-50285996 (musings on safety profile), #msg-56271789 (all-oral trial with BI 207127); Danoprevir (Roche; phase-2b; a/k/a RG7227; f/k/a ITMN-191), a protease inhibitor: #msg-57054424, #msg-57591630 (program probably dead), #msg-55244199, #msg-55244797, #msg-55554201 (transfer of rights to Roche), #msg-53621981, #msg-53624063, #msg-54403876 (PK trial with ritonavir boosting), #msg-52702788 (INFORM-3 delay), #msg-43632598 (first report of liver tox), #msg-45340745 (phase-2b design change and delay), #msg-49046274 (phase-1b data with ritonavir [PR]), #msg-47860488 (phase-1b data with ritonavir [abstract]), #msg-49056848 (ghmm’s musings on ritonavir data), #msg-43185247 (INFORM-1 data from 2009 AASLD); DEB025 (NVS/Debiopharm; phase-3), a cyclophilin inhibitor: #msg-61671677 (final phase-2 data), #msg-56835202 (phase-1b/2a charts and MoA), #msg-46432280 (history); Filibuvir (PFE; phase-2b), a non-nucleoside “thumb” polymerase inhibitor (#msg-54888361); GI-5005 (GlobeImmune; phase-2b), an injectable immunomodulator: #msg-56129933 (phase-2b data); #msg-49171909 (IL-28 B genotype data); IFN-Lambda (BMY; phase-2b), a purportedly more tolerable form of interferon than Pegasys/Pegintron: #msg-61755220 (phase-2b data); Locteron (Biolex; phase-2b), a long-acting interferon made in transgenic plants that may qualify for the 505b2 approval pathway: #msg-61711095 (phase-2b data), #msg-40953698 (manufacturing agreement); nitazoxanide (Romark/Chugai; phase-2a completed): #msg-49791818 (phase-2a data), #msg-55778202 (plans to run combo trial with Intercell vaccine); PSI-7977 (VRUS; phase-2b), a nucleotide polymerase inhibitor (a single-isomer formulation of the defunct, PSI-7851): #msg-61749127 (14-day data fm ‘NUCLEAR’ combo w PSI-938), #msg-57193766 (PR re ‘NUCLEAR’ combo w PSI-938), #msg-58596259 (PR re combo with BMS-750052), #msg-53827604 (phase-2b 1st-line), #msg-61668472 (phase-2b 2nd-line), #msg-49886718 (phase-2a data 1st-line geno-1), #msg-61679544 (phase-2a data 1st-line geno-2/3); RG7128 (Roche/VRUS; phase-2b), a nucleoside polymerase inhibitor: #msg-61784048 (musings on deficiency of MoA), #msg-46762882 (phase-2b overview), #msg-61677141 (high relapse rate in Jump-C phase-2b study), #msg-51072553 (12-week interim safety analysis from PROPEL study in gentotype-1/4), #msg-53179217, #msg-53154180 (“delay” in start of phase-2b in genotype-2/3); TMC435 (Medivir/JNJ; phase-3), a protease inhibitor: #msg-60078852 (phase-3 program), #msg-60210162 (interim phase-2b PILLAR data in first-line setting), #msg-61754182 (interim phase-2b ASPIRE data in second-line setting), #msg-56929106 (musings on interim phase-2b data).


3. Programs in phase-1b/2a with an established MoA: ABT-072 (ABT; phase-2), a non-nucleoside polymerase inhibitor: #msg-58405118 (combo trial with ABT-450); ABT-333 (ABT; phase-2a), a non-nucleoside polymerase inhibitor: #msg-47060142, #msg-42098204; ABT-450 (ABT/Enanta; phase-2a), a protease inhibitor: #msg-61757048 (interim phase-2a data), #msg-58405118 (combo trial with ABT-072); ACH-1625 (ACHN; phase-2a), a protease inhibitor: #msg-61504285 (phase-2a data), #msg-50099890 (phase-1b data table), #msg-50044936, #msg-51176124 (general musings on program); BI 207127 (Boehringer Ingelheim; phase-2a), a non-nucleoside polymerase inhibitor: #msg-56271789, #msg-51499515; BMS-650032 (BMY; phase-2a), a protease inhibitor—see BMS-790052 entry; BMS-790052 (BMY; phase-2a), an NS5A inhibitor being tested in an all-oral combo with PSI-7977 and in combo with BMS-650052 ± SoC: #msg-58596259 (PR re trial with PSI-7977), #msg-61651772, #msg-61483858, #msg-60946871, #msg-55118600 (combo data w BMS-650032), #msg-49176213 (phase-2a data with SoC); GS9190 (GILD; phase-2a), a non-nucleoside polymerase inhibitor with manifold safety and efficacy issues that is being tested with GS9256: #msg-55725066, #msg-52470566, #msg-46036072; GS9256 (GILD, phase-2a), a protease inhibitor that is been tested with GS9190: #msg-55725066, #msg-52702788, #msg-46036072; IDX184 (IDIX; phase-2a), a purine-nucleotide polymerase inhibitor #msg-60417743 (plans for phase-2b), #msg-59734872 (partial removal of FDA clinical hold), #msg-54120531 (phase-2a data), #msg-49115305 (comparison to PSI-7977 data), #msg-39719159, (phase-1b monotherapy data), #msg-49115388, #msg-26915921 (nucleotide/liver-targeted MoA); MK-7009 (MRK; phase-2a), a protease inhibitor: #msg-34337398, #msg-34335327; PPI-461 (Presidio Pharma; phase-1b), an NS5A inhibitor: #msg-61668545 (phase-1b data), #msg-52296077 (history of compound); VX-222 (VRTX; phase-2), a non-nucleoside “thumb” polymerase inhibitor being tested with Telaprevir: #msg-61669471 (interim phase-2 data with Telaprevir), #msg-47242513 (musings on original phase-2 trial design), #msg-49096553 (phase-1b monotherapy data.


4. Very-early-stage programs with an established MoA: ACH-2684 (ACHN; preclinical), a protease inhibitor: #msg-46160360; ACH-2928 (ACHN; preclinical), an NS5A inhibitor: #msg-52524948; AVL-181 and AVL-192 (Avila Therapeutics; preclinical): a pair of related protease inhibitors: #msg-49093995; EDP-239 (Enanta; preclinical): an NS5A inhibitor: #msg-47301187; GS-5885 (GILD; phase-1b): an NS5A inhibitor: #msg-60686677; ‘hyperglycosylated’ interferon (Alios BioPharma; preclinical): #msg-35612425; INX-189 (INHX; phase-1b), a purine nucleotide polymerase inhibitor: #msg-61668669; PSI-938 (VRUS; phase-2a), a purine-analog nucleotide prodrug (see PSI-7977 entry for combination studies): #msg-58513484 (Jan 2011 update), #msg-56049854 (phase-1 data); PSI-661 (VRUS; preclinical; f/k/a PSI-839), a backup to PSI-938 that uses the same active ingredient with a different prodrug: #msg-42245955; TMC649128 (JNJ/Medivir; phase-1): a nucleoside polymerase inhibitor (#msg-59749201); three unnamed compounds with undisclosed MoA’s (GILD; phase-1): #msg-49224935; an unnamed NS5A inhibitor (IDIX; preclinical): #msg-47110147; an unnamed NS5A inhibitor (GSK via Genelabs; status unknown): #msg-33209281, #msg-33211420; an unnamed second-generation protease inhibitor (Roche/ITMN; preclinical): #msg-49783993; an unnamed NS5A inhibitor (VRTX via ViroChem; preclinical): #msg-36022752.


5. Programs in phase-2a or earlier with a novel MoA: AVL-181 (Avila Therapeutics; preclinical), a small-molecule drug that purportedly binds to an infected hepatocyte: #msg-47113598; CF102 (Can-Fite; phase-1/2), a polymerase inhibitor that purportedly induces apoptosis: #msg-39588570; Clemizole (Eiger Biopharmaceuticals; phase-1), an old antihistamine repositioned as an NS4B inhibitor: #msg-51892107; CTI-1027 (Conatus; phase-2b), a compound with an unclear MoA: #msg-60068380; IL-7 (Cytheris; phase-1/2) an injectable immunomodulator: #msg-33152073; IMO-2125 (IDRA; phase-1), a TLR9 agonist: #msg-61716577; ITX5061 (iTherX; phase-2a), MoA unknown: #msg-35319690; MB11362 (Roche/MBRX; preclinical), MoA undisclosed: #msg-38456136; NOV-205 (NVLT, phase-2), supposedly an immunomodulator: #msg-48269914; SCY-635 (Scynexis; phase-1b), a cyclophilin inhibitor: #msg-46669845; SD-101 (DVAX; phase-1b), a TLR9 agonist: #msg-45932364; SPC3649 (Santaris; phase-2), MoA based on microRNA: #msg-54718042; an unnamed entry inhibitor (PGNX; preclinical): #msg-38519885; an unnamed miR-122 inhibitor (GSK/Regulus; preclinical): #msg-47081015.


6. Programs on the back burner: A-831 (AZN; status unknown), an NS5A inhibitor: #msg-49610323; ACH-1095 (ACHN; preclinical), an NS4A inhibitor that is effectively dead based on ACHN’s CC on 8/19/10 (GILD previously dropped the compound while nominally retaining the right to opt back in: #msg-41217537); ANA773 (ANDS; phase-1), an oral TLR7 modulator that ANDS discontinued in Jun 2009 and is nominally available for partnering: #msg-38418158; IDX375 (IDIX; phase-1), a non-nucleoside “palm” polymerase inhibitor: #msg-60428047 (confirmation of back-burner status), #msg-45350536 (phase-1 PK data); IFN-alpha-XL (FLML; phase-2a): #msg-44688995; MK-3281 (MRK; phase-1), a non-nucleoside “thumb” polymerase inhibitor: #msg-50798497; SCH 900518/narlaprevir (MRK; phase-2a), a protease inhibitor originally owned by Schering-Plough that MRK discontinued following a pipeline pruning: #msg-47224801 (3/1/10 announcement of discontinuation), #msg-43169835 (interim phase-2a data), #msg-34338549 (final phase-1b data); Taribavirin (Kadmon; phase-2b), a prodrug of ribavirin that has been floating around for a long time: #msg-56271960 (sale by VRX), #msg-38280961 (musings on final phase-2b data), #msg-37299101 (detailed 60-week data); VX-813/VX-985 (VRTX; phase-1/preclinical), protease inhibitors that were previously touted as the backups to Telaprevir: #msg-45333927.


JMHO, FWIW