Biotech Values

[DewDiligence]

HCV: Most Likely to Succeed (IMHO)

[Updated entry for Telaprevir/ VX-222 combination.]


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 submission in progress) and Boceprevir (MRK; phase-3 completed/NDA submission late 2010). 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).

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-55917427 (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-54315761 (phase-3 REALIZE study—data table); #msg-54152015 (phase-3 REALIZE study—PR); #msg-48759554 (phase-2b PROVE-3 study).

Boceprevir in the first- and second-line settings: #msg-56129390, #msg-52949888 (PR’s with results of SPRINT-2 and RESPOND-2 studies); #msg-53025126 (exclusion of null responder patients from RESPOND-2 study); #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-56271789 (all-oral trial with BI 207127); Danoprevir (Roche; phase-2b; a/k/a RG7227; f/k/a ITMN-191), a protease inhibitor: #msg-55244199, #msg-55244797, #msg-55554201 ([bearish, IMO] 2010 transfer of rights to Roche), #msg-53621981, #msg-53624063, #msg-54403876 ([bearish, IMO] 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); Debio 025 (NVS/Debiopharm; phase-2b), a cyclophilin inhibitor: #msg-46432280; 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): #msg-50805665, #msg-43360640 (phase-2a/2b trial description), #msg-34768182 (BMY partnership), #msg-43123220 (final phase-1b data); 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 (phase-2a data), #msg-55778202 (plans to run combo trial with Intercell vaccine); PSI-7977 (VRUS; phase-2b), a nucleotide polymerase inhibitor that’s a single-isomer formulation of PSI-7851: #msg-53827604 (phase-2b design), #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-53179217, #msg-53154180 (“delay” in start of phase-2b in genotype-2/3), #msg-43185247 (INFORM-1 data from AASLD 2009); TMC435 (Medivir/JNJ; phase-2b), a protease inhibitor: #msg-56129587, #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-56272166, #msg-35708745; ACH-1625 (ACHN; phase-2a), a protease inhibitor: #msg-55036061 (phase-2a trial), #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-56271789, #msg-51499515; BMS-650032 (BMY; phase-2a), a protease inhibitor that’s being tested in an all-oral trial with BMS-790052: #msg-55118600, #msg-44700187; BMS-790052 (BMY; phase-2a), an NS5A inhibitor that’s being tested in an all-oral trial with BMS-650032: #msg-55118600, #msg-44700187 (phase-2 combination trial), #msg-49176213 (phase-2a monotherapy data from 2010 EASL); 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 that is on clinical hold due to liver tox in a combo study with IDX320: #msg-54120531 (clinical-hold announcement and final top-line phase-2a data), #msg-54130390 (musings on the clinical hold), #msg-49115305 (comparison to PSI-7977 data), #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 that is currently on clinical hold due to liver tox in a combo study with IDX184: #msg-54120531 (clinical-hold announcement and phase-1b monotherapy data), #msg-54130390 (musings on the clinical hold), #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), a non-nucleoside “thumb” polymerase inhibitor being tested with Telaprevir: #msg-56508419 (ribavirin added to Telaprevir/VX-222 combination trial), #msg-55917569 (termination of low dose in combination trial), #msg-47242513 (musings on original design of combination 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-1b), a purine nucleotide polymerase inhibitor: #msg-56132831 (phase-1b trial), #msg-53933560 (phase-1a data); PSI-938 (VRUS; phase-1b), a purine-analog nucleotide prodrug: #msg-56049854; 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; 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-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; 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; 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