Replies to post #94017 on Biotech Values

[bladerunner1717]

Dew,

How do you see GSK/IDIX in all of this? If "Quad" succeeds or TMC278 with Truvada succeeds or both, how much of a market is left for GSK/IDIX? How do you expect all this to play out?


Bladerunner

[DewDiligence]

JNJ/GILD’s TMC278+Truvada combo pill moved a step closer to
realization today with JNJ’s announcement that TMC278 met its
primary endpoint of non-inferiority to Sustiva in two phase-3
studies that tested TMC278+Truvada vs Sustiva+Truvada. JNJ’s
NDA submission for TMC278 is expected in 3Q10; following FDA
acceptance of JNJ’s NDA for review, GILD will submit the NDA
for the combo pill in 4Q10.

http://finance.yahoo.com/news/Gilead-Provides-Update-on-bw-2235377411.html?x=0&.v=1

›Gilead Provides Update on Development of Fixed-Dose Regimen of Truvada and Tibotec Pharmaceuticals' TMC278

• Pivotal Phase III Studies of TMC278 Met Primary Objective -

• Gilead Working to Identify Fixed-dose Regimen Candidate Suitable for Registration -

Tuesday April 20, 2010, 8:51 am EDT

FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) provided an update today on the development of the fixed-dose combination of Truvada® (emtricitabine and tenofovir disoproxil fumarate) and Tibotec Pharmaceuticals’ investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278 (rilpivirine hydrochloride, 25 mg). As part of its First Quarter 2010 earnings call, Johnson & Johnson, which owns Tibotec Pharmaceuticals, announced today that the two pivotal Phase III studies evaluating TMC278 as a treatment for HIV in treatment-naïve patients met the primary efficacy objective of non-inferiority as compared to efavirenz based on the proportion of patients achieving HIV RNA levels of less than 50 copies/mL at 48 weeks. Johnson & Johnson also announced that full study results will be presented at a scientific meeting later this year, and that the submission of TMC278 for regulatory review is on track for the third quarter of this year.

Gilead is working to identify a formulation of the fixed-dose combination of Truvada and TMC278 that meets bioequivalence. A bioequivalence study is required to demonstrate that a co-formulated product results in the same levels of medication in the blood as achieved when the individual products are dosed simultaneously as separate pills.

In July 2009, Gilead announced that it had entered into a license and collaboration agreement with Tibotec Pharmaceuticals for the development and commercialization of a new once-daily fixed-dose antiretroviral regimen containing Truvada and TMC278 for treatment-naïve HIV-infected individuals. The companies are also working toward an agreement to make the fixed-dose combination of Truvada and TMC278 available in the developing world. If approved, the new product would become the second complete antiretroviral treatment regimen for HIV available in a single tablet taken once daily [the first such product is, of course, Atripla].‹

[DewDiligence]

The New Battle Lines in HIV (GILD/JNJ/IDIX/GSK)

[Updates:
TMC278 phase-3 results reported on JNJ’s 1Q10 CC (#msg-49224079);
HIV market data from GILD’s 1Q10 CC (#msg-49275972);
major rewrite of IDX899 section to include GSK’s “nuke-sparing” trial.]


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-49275972, #msg-26915314). 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 their resistance profile and tolerability leave room for improvement. Reyataz from BMY and Kaletra from ABT, the two biggest-selling PI’s, have been steadily losing market share, even as they continue top grow modestly in dollar sales.

NNRTI’s and II’s that can be dosed qD are where the action is likely to be. The leading candidates to gain traction (IMHO) are as follows.


1. TMC278, a qD NNRTI from JNJ that recently completed two successful phase-3 trials in which TMC278 was found to be non-inferior to Sustiva (#msg-49224079, #msg-30789106, #msg-31354706). TMC278 is similar to JNJ’s Intelence, an NNRTI launched in 2008 that has the drawback of requiring BID dosing with food.

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), TMC-278 merits the top spot in the ranking in this post because it has a chance to reach the market much sooner than Quad or any other competitive option.


2. Quad/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.*

Quad is the name for the 4-drug combo that includes Elvitegravir, the two drugs in Truvada, and GILD’s proprietary PK-booster called Cobicistat (f/k/a GS9350). Quad started phase-3 in Apr 2010 (#msg-48883214); in phase-2, Quad was non-inferior to Atripla at 24 weeks (#msg-45203412, #msg-46731576). Standalone Elvitegravir is also in phase-3, where it is being tested head-to-head vs Isentress (#msg-30900183). Clearly, GILD has an economic incentive to prefer Quad to the TMC-278 + Truvada combination GILD is developing jointly with JNJ; however, I rank Quad second in this post because the TMC-278 + Truvada combination has a chance to reach the market considerably sooner than Quad.


3. IDX899, a qD NNRTI licensed by GSK from IDIX (and now owned by the GSK/PFE joint venture called ViiV Healthcare): #msg-43254006, #msg-37080917, #msg-37087221. IDX899 will start two phase-2b trials in 2Q10 testing IDX899 against Sustiva (first-line setting) or Intelence (second-line setting) when each drug is added to Truvada. What’s especially exciting, IMO, is that GSK is planning a separate phase-2b nuke-sparing trial in which IDX899 will be added to GSK’s integrase inhibitor, S/GSK1349572: #msg-48913630, #msg-48915175.

In a phase-1b/2 monotherapy study, IDX899 showed antiviral efficacy at extremely low doses (#msg-31925486, #msg-31944395), which fosters its ability to be formulated in an all-in-one pill with a small form factor.

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; Isentress evidently does not benefit from boosting with ritonavir.