Biotech Values

[DewDiligence]

HCV: Most Likely to Succeed (IMHO)

[Updated entries for Boceprevir and Telaprevir, including table comparing
phase-3 Telaprevir and Boceprevir results in first- and second-line settings.]


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; phase-3 almost completed/NDA submission in progress) and Boceprevir (MRK; phase-3 completed/NDA submission late 2010). Between these two, I consider Telaprevir the favorite for the reasons mentioned in the prologue of #msg-52949888; however, this assessment could conceivably change when MRK presents the complete phase-3 dataset for Boceprevir at the AASLD conference in Oct-Nov 2010. The table in #msg-52978824 compares the Telaprevir and Boceprevir data in the first- and second-line settings with the caveat that the trial designs and patient pools for the two sets of trials have some differences.

Telaprevir in the first-line setting: #msg-50595952 (results of phase-3 ADVANCE study—PR); #msg-50595752 (results of ADVANCE study—data table); #msg-50633310 (tepid investor reaction/Stevens-Johnson Syndrome); #msg-26228377 (ILLUMINATE—the smaller of the two phase-3 trials); #msg-52754317 (phase-3b study of TID vs BID dosing); #msg-43114192 (‘C208’ phase-2 study of BID vs TID dosing); #msg-29019931 (summary of results from phase-2b); #msg-28746843 (detailed results from phase-2b).

Telaprevir in the second-line setting:: #msg-32901932 (phase-3 REALIZE study); #msg-48759554 (phase-2b PROVE-3 study).

Boceprevir in the first- and second-line settings: #msg-52949888 (PR with results of SPRINT-2 and RESPOND-2 studies); #msg-50187183 (NDA submission will exclude phase-3 anemia study; #msg-52963584, #msg-37298085 (questions about anemia and EPO use); #msg-31190433 (musings on SPRINT-1 phase-2b data).


2. Other programs in phase-2b or later: BI 201335 (Boehringer Ingelheim; phase-2b), a protease inhibitor: #msg-50285996 (safety profile), #msg-47877812 (abstract from 2010 EASL), #msg-42086185 (abstract from 2009 AASLD), #msg-33564560 (phase-2b design), #msg-51243571 (all-oral trial with BI 207127); Debio 025 (NVS/Debiopharm; phase-2b), a cyclophilin inhibitor: #msg-46432280; GI-5005 (GlobeImmune; phase-2b), an injectable immunomodulator: #msg-49095438 (phase-2b data); #msg-49171909 (IL-28 B genotype data); IFN-Lambda (BMY/ZGEN; phase-2b): #msg-50805665, #msg-43360640 (phase-2a/2b trial description), #msg-34768182 (BMY partnership), #msg-43123220 (final phase-1b data); ITMN-191 (Roche/ITMN; phase-2b; a/k/a Danoprevir/RG7227), a protease inhibitor: #msg-49099924 (phase-2b data without ritonavir), #msg-52702788 (INFORM-3 delay), #msg-46797334 (Dew’s bearish take), #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-44330890 (slides from 2009 HepDart), #msg-43185247 (INFORM-1 data from 2009 AASLD); Locteron (Biolex; phase-2b), a long-acting interferon made in transgenic plants that may qualify for the 505b2 approval pathway: #msg-49286341 (interim phase-2b data from 2010 EASL), #msg-37298340 (final phase-2a data), #msg-40953698 (manufacturing agreement); nitazoxanide (Romark/Chugai; phase-2a completed): #msg-49791818; PSI-7977 (VRUS; phase-2a completed), a nucleotide polymerase inhibitor that’s a single-isomer formulation of PSI-7851: #msg-49886718 (phase-2a data), #msg-49115305 (comparison to IDX184 data), #msg-40115833 (phase-1b data for PSI-7851); RG7128 (Roche/VRUS; phase-2b), a nucleoside polymerase inhibitor: #msg-46762882 (phase-2b overview), #msg-51072553 (12-week interim safety analysis from PROPEL trial in gentotype-1/4), #msg-43185247 (INFORM-1 data from AASLD 2009); TMC435 (Medivir/JNJ; phase-2b), a protease inhibitor: #msg-52204240 (24-week data from phase-2b), #msg-50276630 (safety signals), #msg-49286281 (presentations at 2010 EASL), #msg-43361309 (overview of phase-2 program at 2009 AASLD), #msg-37298740 (phase-2a data at 2009 EASL).


3. Programs in phase-1b/2a with an established MoA: ABT-072 (ABT; phase-2), a non-nucleoside polymerase inhibitor: #msg-47086871; #msg-47060142; ABT-333 (ABT; phase-2a), a nucleoside polymerase inhibitor: #msg-47060142, #msg-42098204; ABT-450 (ABT/Enanta; phase-2a), a protease inhibitor: #msg-47060142, #msg-35708745; ACH-1625 (ACHN; phase-1b), a protease inhibitor: #msg-50099890 (phase-1b data table), #msg-50044936, #msg-51176124 (general musings on program); ANA598 (ANDS; phase-2a), a non-nucleoside “palm” polymerase inhibitor: #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 207127 (Boehringer Ingelheim; phase-2a), a non-nucleoside polymerase inhibitor: #msg-51499515; BMS-650032 (BMY; phase-2a), a protease/NS3 inhibitor that’s being tested in an all-oral trial with BMS-790052: #msg-44700187, #msg-40361108; BMS-790052 (BMY; phase-2a), an NS5A inhibitor that’s being tested in an all-oral trial with BMS-650032: #msg-44700187 (phase-2 combination trial), #msg-49176213 (phase-2a monotherapy data from 2010 EASL); GS9256 (GILD, phase-2a), a protease inhibitor that has been tested with GS9190: #msg-52702788, #msg-46036072; IDX184 (IDIX; phase-2a), a nucleotide polymerase inhibitor: #msg-49096739, #msg-49003061 (interim phase-2a data [table]), #msg-49096739 (interim phase-2a data [PR]), #msg-49115305 (comparison to PSI-7977 data), #msg-52028450, #msg-49731578 (combination with IDX320), #msg-39719159, (phase-1b monotherapy data), #msg-49115388, #msg-26915921 (nucleotide/liver-targeted MoA), #msg-49055353, #msg-47954632 (in vitro data in combination with other IDIX drugs); IDX320 (IDIX; phase-1b), a macrocyclic protease inhibitor: #msg-51127676 (phase-1b monotherapy trial), #msg-52028450, #msg-49731578 (combination with IDX184), #msg-51165077 (half-life and dosing frequency), #msg-49055353, #msg-47954632 (PK, DDI, in vitro data in combination with other IDIX drugs); IFN-alpha-XL (FLML; phase-2a): #msg-44688995; MK-7009 (MRK; phase-2a), a protease inhibitor: #msg-34337398, #msg-34335327; PPI-461 (Presidio Pharma; phase-1b), an NS5A inhibitor: #msg-52296077; VX-222 (VRTX; phase-2; f/k/a VCH-222), a non-nucleoside “thumb” polymerase inhibitor (acquired from ViroChem) being tested with Telaprevir+SoC as well as with Telaprevir alone: #msg-47189924 (combo trial with Telaprevir), #msg-47242513 (musings on combo trial), #msg-49096553 (phase-1b monotherapy data [PR]), #msg-47879091 (phase-1b monotherapy data [abstract]).


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; ‘hyperglycosylated’ interferon (Alios BioPharma; preclinical): #msg-35612425; IDX375 (IDIX; phase-1), a non-nucleoside “palm” polymerase inhibitor: #msg-45350536 (phase-1 PK data), #msg-49055353, #msg-47954632 (in vitro data in combination with other IDIX drugs); INX-189 (INHX, phase-1), a nucleotide polymerase inhibitor: #msg-50110448; PSI-938 (VRUS; phase-1b), a purine-analog nucleotide prodrug: #msg-52714527; PSI-661 (VRUS; preclinical; f/k/a PSI-839), a purine-analog nucleotide prodrug billed as the successor to PSI-938: #msg-42245955; 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: ACH-1095 (ACHN; preclinical), an NS4A inhibitor that GILD dropped while retaining the right to opt back in: #msg-41217537; 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-2): #msg-46034554; IL-7 (Cytheris; phase-1/2) an injectable immunomodulator: #msg-33152073; IMO-2125 (IDRA; phase-1), a TLR9 agonist: #msg-49094332; 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; preclinical), MoA based on microRNA: #msg-44177354; 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; Albuferon/Zalbin (HGSI/NVS; post-BLA): #msg-51249417 (no-go with FDA), #msg-49185693 (EU MAA withdrawn), #msg-36140577 (phase-3 data), #msg-48180658, #msg-48213975 (phase-2 data with monthly dosing); ANA773 (ANDS; phase-1), an oral TLR7 modulator that ANDS discontinued in Jun 2009 and is nominally available for partnering: #msg-38418158; GS9190 (GILD; phase-2a), a non-nucleoside polymerase inhibitor with manifold safety and efficacy issues that had been tested with GS9256: #msg-52702788, #msg-46036072; 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 (VRX; phase-2b), a “legacy” prodrug of ribavirin that has been floating around for a long time: #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