The New Battle Lines in HIV (GILD/JNJ/IDIX/GSK/PFE)
[Swapped paragraphs #1 and #2 due to the new GILD-JNJ collaboration to develop a Truvada+TMC-278 combo pill. (In an earlier version of this write-up, I removed the RDEA-806 program from RDEA (#msg-37680575).]
GILD’s Truvada franchise is so firmly established as the backbone of therapy in the early lines of treatment that there is little to no chance of anything replacing it in the near future (#msg-26915314; start of phase-3: #msg-35137606). Moreover, Truvada and BMY’s Sustiva have been combined into a single pill—Atripla—that is taken once daily and sets a standard for convenience (and hence compliance) that a twice-daily regimen cannot hope to match. Thus, from a business standpoint, the question is to ask is: Which qD drugs, if any, will be able to supersede Sustiva as the favored “third” drug in Truvada-based regimens?
Inasmuch as Truvada consists of two nucleoside reverse-transcriptase inhibitors—Viread and Emtriva—the third drug in a Truvada-based cocktail will clearly come from a different class. The main options are non-nucleoside reverse-transcriptase inhibitors (NNRTI’s), protease inhibitors (PI’s) and integrase inhibitors (II’s).
However, the market has been moving away from the use of PI’s in early lines of therapy because they have a relatively poor resistance profile and mediocre tolerability. Reyataz from BMY and Kaletra from ABT, the two biggest-selling PI’s, have been steadily losing share (e.g. #msg-35109525).
Thus, NNRTI’s and II’s that can be dosed qD are where the action will be. The leading candidates to gain traction (IMHO) are as follows.
1. TMC278, a qD NNRTI from JNJ in phase-3 (start of phase-3: #msg-30789106; phase-2 data: #msg-31354706.) TMC278 is similar to JNJ’s Intelence (a/k/a/ TMC125), an NNRTI already on the market that has the drawback of being dosed BID. TMC278 catapulted into first place in the ranking in this post when JNJ and GILD inked a collaboration to combine it with Truvada into a single qD pill (#msg-39660789). Although GILD has an economic incentive to develop an all-in-one pill consisting entirely of GILD’s own drugs (see paragraph #2 below), the Truvada+TMC-278 combination deserves the top spot in the ranking in this post because it has a chance to reach the market much sooner than any alternative.
2. Quadro/Elvitegravir from GILD. Elvitegravir is an II similar to MRK’s Isentress, which is doing about $500M in annualized sales; however, Elvitegravir has the crucial advantage of being dosed qD with help from a PK-boosting agent.* Quadro is the name for the 4-drug combo that includes Elvitegravir, Truvada, and GILD’s proprietary PK-booster called GS9350. Standalone Elvitegravir is in phase-3 (#msg-30900183) and Quadro is in phase-2 (#msg-37122536). Clearly, GILD has an economic incentive to prefer Quadro to the Truvada+TMC-278 combination being developed in collaboration with JNJ; however, I rank Quadro behind the JNJ collaboration because TMC-278 is in phase-3 while Quadro is in phase-2.
3. IDX899, licensed by GSK from IDIX and now owned by the joint venture between GSK and PFE: #msg-37066684 (PR announcing the JV) , #msg-37080917 (musings by Dew), #msg-37087221 (musings by Dow Jones). IDX899 is a qD NNRTI about to start phase-2 (#msg-31925486). It has antiviral efficacy even at extremely low doses (#msg-31944395), which fosters its ability to be combined with other HIV drugs in a single pill with a small form factor. Moreover, IDX899 has a stronger barrier to resistance than Sustiva (#msg-35431633) and it lacks cross-resistance to Sustiva, which preserves the option for patients to use Sustiva in a subsequent line of therapy.
*MRK is testing Isentress with qD dosing in a phase-3 trial and could submit an sNDA in 2011; however, I consider this trial a long shot.
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