Replies to post #99227 on Biotech Values

[DewDiligence]

Reuters doesn’t get it vis-à-vis GSK’s ‘572:

http://www.reuters.com/article/idCNLDE66J0O020100721

Glaxo will have the option of combining '572 with various other AIDS drugs, including its established product Combivir.

Combining a promising new HIV drug with the archaic Combivir would be throwing good money after bad. I can almost guarantee this is not GSK’s main objective for ‘572.

[DewDiligence]

GSK Reports Phase-2b Data of ‘572 Integrase Inhibitor

[S/GSK1349572 (nickname ‘572) is the HIV integrase inhibitor that GSK plans to test in a “nuke-sparing” trial with IDIX’s IDX899 (#msg-48915175). GSK licensed the drug from Shionogi, and the author of this PR is the JV known as Shionogi-ViiV Healthcare LLC, which recently announced that ‘572 was advancing to phase-3 (#msg-52482079).

‘572 is the only unboosted qD integrase inhibitor to advance as far as phase-3. (GILD’s Elvitegravir requires PK boosting and MRK’s Isentress is dosed BID.) All told, ‘572 looks like a promising compound and a good one for IDIX to have its HIV future hitched to.]

http://finance.yahoo.com/news/ShionogiViiV-Healthcare-LLC-prnews-1350579677.html?x=0&.v=1

›Shionogi-ViiV Healthcare LLC Presents Positive Data on Investigational Once-Daily Integrase Inhibitor at International AIDS Conference

• Positive Antiviral Responses Demonstrated in Interim 16 Week Analysis from SPRING-1 Study

• Antiviral activity shown by S/GSK1349572 in treatment-experienced subjects resistant to raltegravir from VIKING Study

Source: Shionogi-ViiV Healthcare LLC
July 22, 2010, 8:30 am EDT

VIENNA, July 22 /PRNewswire/ -- Shionogi-ViiV Healthcare LLC today reported data from two Phase IIb studies showing that its once-daily, unboosted investigational integrase inhibitor, S/GSK1349572 ('572), exhibited potent antiviral activity in treatment-naive HIV subjects as well as in treatment-experienced subjects resistant to raltegravir (RAL). These clinical results and additional findings on the virologic profile of '572 were presented at the XVIII International AIDS Conference in Vienna, Austria. '572 is the only once-daily, unboosted integrase inhibitor in Phase IIb clinical development.

"There remains a significant need for additional medicines that can help address the complex treatment issues for HIV, and also help simplify treatment regimens for patients. As a once-daily, unboosted integrase inhibitor, '572 could provide an important therapy for patients living with HIV," stated Dr. John Pottage, Chief Scientific and Medical Officer of ViiV Healthcare. "We look forward to confirming the safety and efficacy of this compound in Phase III studies, which are expected to begin by the end of the year."

"We are very pleased with the progress of '572 in collaboration with ViiV Healthcare. We look forward to completing the clinical development process with '572 and providing benefit to the millions of HIV-infected patients throughout the world," said Dr. Tsutae "Den" Nagata, Chief Medical Officer, Shionogi & Co., Ltd.

Overall, five abstracts were presented during the conference relating to the integrase inhibitor program, which is being developed by Shionogi-ViiV Healthcare. Highlights from presentations on '572 are described below.

SPRING-1 Study Data (Abstract Number THLBB205)

SPRING-1 is an ongoing Phase IIb, multicenter, partially-blinded, dose-ranging study comparing '572 to efavirenz (EFV) in 205 treatment-naive subjects. Individuals were randomized 1:1:1:1 to 10 mg, 25 mg or 50 mg of '572 or EFV 600mg once daily in combination with either tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). Eighty-six percent of subjects were male, 20 percent were non-white and 26 percent had HIV-1 RNA levels >100,000 copies/mL.

Key SPRING-1 results through 16 weeks included the following:

• At Week 16, more than 90 percent of subjects treated with '572 achieved viral suppression (HIV-1 RNA levels < 50 copies/mL) compared to 60 percent of subjects treated with EFV. The percentage of subjects who achieved viral suppression was 96 percent, 92 percent and 90 percent for the 10 mg, 25 mg and 50 mg '572 doses, respectively.

• Time to viral suppression was significantly shorter for subjects treated with '572 compared to EFV (p <0.001). By Week 4, 66 percent of subjects treated with '572 were suppressed, compared to 18 percent of subjects treated with EFV.

• Two virologic failures occurred, one in the '572 treatment group and one in the EFV treatment group. No integrase-associated substitutions in genotype or changes in INI susceptibility (to either '572 or RAL) were observed in the subject receiving '572 with virologic failure.

• '572 was generally well tolerated. Drug-related adverse events of moderate or higher intensity were reported in more subjects receiving EFV (9/50, 18 percent of subjects) than '572 (9/155, 6 percent of subjects). No drug-related moderate to severe adverse event occurred in more than one subject receiving '572. The most frequent category of these events in the EFV and '572 arms were gastrointestinal (4 percent versus 2 percent, respectively), which were the only events that occurred in >1 subject receiving '572. Other events occurring in >1 subject treated with EFV were psychiatric (6 percent) and rash (4 percent) disorders. No dose-relationship for adverse events was noted across '572 doses. More subjects receiving EFV (n=4, 8 percent) withdrew from treatment due to adverse events compared to '572 (n=1, <1 percent).

VIKING Study Data (Abstract Number MOAB0105)

The VIKING study is an ongoing Phase IIb multicenter, open-label, single arm study designed to assess the antiviral activity, safety and tolerability of '572, as short-term functional monotherapy and over a 24-week treatment period with optimized background therapy in treatment-experienced, HIV-infected adult subjects with RAL resistance. Genotypic and phenotypic changes in HIV integrase were also evaluated.

The study enrolled 27 subjects with screening plasma HIV-1 RNA greater than or equal to 1000c/mL showing genotypic resistance to RAL and at least two other antiretroviral classes. All subjects had RAL-associated mutations at screening. Subjects received '572 50mg QD while continuing their failing regimen (without RAL) to Day 11 when the background regimen was optimized, where feasible, and '572 continued.

Key VIKING study results through Day 11 included the following:

• The majority of subjects treated with '572 demonstrated positive antiviral response, as measured by plasma HIV-1 RNA <400 c/mL or decline of >0.7 log10, despite the high level resistance to RAL.

• Viral response differed according to baseline integrase inhibitor genotype. Responders included all 16 subjects with N155H, Y143H or Q148 single mutant pathways, three of four subjects with Q148 plus one secondary mutation and two subjects with other mutations. None of the subjects with Q148 plus two or more secondary mutations showed antiviral response.

• '572 was generally well tolerated. The most frequent adverse events were diarrhea (N = 3) and insomnia (N = 3).

• Few integrase genotypic changes were observed, and minimal changes in '572 susceptibility were observed, suggesting minimal virus evolution over the 11-day observation period. On Day 1, 25 of 27 subjects had virus with RAL-associated signature mutations. By Day 11, of 18 subjects with evaluable virus, 17 had phenotypic susceptibility changes to '572 less than two-fold. The additional paired viral isolate had a susceptibility change of approximately six-fold.

Additional Data on '572 (Abstract Number MOPE0032)

Additional data presented supported the potency of '572 when tested against a broad panel of HIV isolates in peripheral blood mononuclear cells and monocyte-derived-macrophages independent of HIV subtype. These observations further support clinical development of '572 across all HIV-1 subtypes.

Further study is necessary to determine conclusively the efficacy, safety, and resistance profile of '572.‹

[DewDiligence]

GSK Starts Phase-3 Trials for ‘572 Integrase Inhibitor

[S/GSK1349572 (nickname ‘572) is an HIV integrase inhibitor that GSK (d/b/a/ Shionogi-ViiV Healthcare) hopes can supplant MRK’s Isentress. (‘572 is also a potential candidate for combination with IDIX’s IDX899, but that’s not the subject of this PR.) Phase-2b data for ‘572 is in #msg-52728888 and #msg-52730834.

Two phase-3 trials, one in the first-line and one in the second-line, will test ‘572 vs Isentress when each is added to a standard dual-nuke backbone. The primary and secondary endpoints, described below, are typical for phase-3 HIV trials. The goal is non-inferiority of ‘572 to Isentress, the idea being that qD dosing (which Isentress does not have) will enable ‘572 to be incorporated into an Atripla-like combo pill. (GILD’s Elvitegravir, an integrase inhibitor in phase-3 that’s a component of ‘Quad’, requires PK-boosting to be given qD.)]

http://finance.yahoo.com/news/ShionogiViiV-Healthcare-LLC-prnews-1547763028.html?x=0&.v=1

›Phase III Treatment-naive and Treatment-experienced Trials Underway for S/GSK1349572 ('572)

Source: Shionogi-ViiV Healthcare LLC
October 21, 2010, 4:00 am EDT

LONDON, Oct. 21 /PRNewswire/ -- Shionogi-ViiV Healthcare LLC today announced the start of the Phase III clinical programme evaluating its once-daily, unboosted investigational integrase inhibitor, S/GSK1349572 ('572). The Phase III clinical programme, which began this month, includes two studies (SPRING-2 and SAILING) that will evaluate '572 in both treatment-naive patients and treatment-experienced, but integrase-naive patients.

"Progression of one of our lead pipeline compounds into late stage development for use in treatment-naive and treatment-experienced patients is an important milestone for ViiV Healthcare in its first year and ultimately we hope for those living with HIV. We believe that this clearly demonstrates the benefit of our 100% focus on HIV and commitment to delivering new or improved treatment options," stated Dr. John Pottage, Chief Scientific and Medical Officer, ViiV Healthcare.

"We are pleased to see '572 progressing into Phase III clinical trials and are optimistic about its potential for HIV-infected patients," said Dr. Sapan Shah, President & CEO, Shionogi Inc. "As the only once-daily, unboosted integrase inhibitor in Phase III clinical development, '572 may help address certain treatment challenges that continue to face people living with HIV."

About the Phase III Trials

SPRING-2 Study Design (ING113086)

SPRING-2 is a Phase III, randomized, blinded, active-controlled, multicenter, parallel group, non-inferiority study. The study will include approximately 788 HIV-1 infected treatment-naive patients. The non-inferiority study will compare efficacy and safety outcomes of '572 and raltegravir [Isentress] (RAL); both treatment arms will be administered with investigator-selected dual nucleoside reverse transcriptase inhibitor therapy (either ABC/3TC or TDF/FTC) [i.e. the dual-nuke backbone will be either Truvada or Epzicom].

The primary objective for SPRING-2 will be to demonstrate the antiviral activity of '572 50mg administered once-daily compared to RAL 400mg administered twice daily over 48-weeks. Secondary objectives include the assessment of antiviral activity of '572 compared to RAL at 96-weeks, to compare the tolerability, long-term safety and antiviral and immunologic activity of '572 to RAL, and to evaluate viral resistance in subjects experiencing virological failure.

SAILING Study Design (ING111762)

SAILING is a Phase III, randomized, double-blind, active-controlled, multicenter, parallel group, non-inferiority study. The study will include approximately 688 HIV-1 infected treatment-experienced, integrase-naive subjects. The non-inferiority study will assess the antiviral efficacy of '572 compared to RAL [Isentress].

The primary objective for SAILING will be to demonstrate the antiviral efficacy of '572 50mg once-daily compared to RAL 400mg twice-daily both in combination with a background regimen consisting of one to two fully active agents at 48-weeks. Secondary objectives will evaluate the long-term antiviral activity, pharmacokinetics (PK), the relationship between PK and antiviral activity, tolerability and safety of '572 versus RAL.‹