Gilead interim ELECTRON and QUANTUM SVR4 data...

Posted 4/19/12 on ClinicaSpace.com - Good news for patients, providers and of course Gilead today at EASL. Not so great for interferon, at least regarding it's place in HCV therapy where it increasing looks like it will be niched to specific special populations.  Gilead's Phase II ELECTRON trial looking at 12 weeks of GS-7977 + RBV posted a SVR4 rate of 88% in genotype 1 patients. Three other arms - including the very-hard-to-treat null responder patients - will be presented later this week. QUANTUM, also a Phase II trial, looking at 12 and 24 week regimens of GS-7977 + RBV in genotype 1, 2 and 3 patients with and without cirrhosis. Data was available only for the 12 week genotype 1 arm, 4 weeks post therapy (SVR4), which garnered a 59% SVR4. It's not clear how many of the 17 patients in the analysis were cirrhotic, but I'm sure that information is forthcoming. It will be interesting to see that breakdown, and if the cirrhotic patient would benefit from 12 additional weeks of GS-7977 + RBV. 

Gilead Sciences, Inc. (GILD)-Bristol-Myers Squibb Company (BMY)'s Experimental Hepatitis C Drug Cured 88% Post-Therapy

4/19/2012 7:22:40 AM

BARCELONA, Spain, Apr 19, 2012 (BUSINESS WIRE) -- Gilead Sciences, Inc. GILD -0.15% today announced interim data from the Phase 2 ELECTRON study examining the investigational once-daily oral agent GS-7977 plus ribavirin (RBV) in treatment-naive patients with genotype 1 chronic hepatitis C virus (HCV) infection. Of the 25 patients who completed 12 weeks of treatment with the GS-7977-based regimen, 88 percent of patients (n=22/25) remained HCV RNA undetectable four weeks after completion of treatment. Three patients experienced viral relapse. These findings are being presented this week during a poster session (Poster #1113) at the 47th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2012) in Barcelona, Spain.

"These preliminary results suggest that 12 weeks of therapy with once-daily oral GS-7977 and ribavirin may be enough to cure hepatitis C in many genotype 1 patients, including those who are currently not candidates to receive interferon," said Professor Edward Gane, MD, Deputy Director and Hepatologist, New Zealand Liver Transplant Unit, Auckland City Hospital in New Zealand, and principal investigator of the ELECTRON study. "Further investigation of GS-7977 in a variety of patient populations and combinations will be important in assessing the drug's potential as part of an all-oral regimen for hepatitis C."

Results from three additional arms of the ELECTRON study examining GS-7977-based therapy in various patient populations are also being presented this week at the International Liver Congress. These include null responder genotype 1 patients, and genotype 2 and genotype 3 patients, both treatment-naive and prior non-responders.

Overall, GS-7977 was well tolerated and exhibited a favorable safety profile. No patients experienced viral rebound during treatment. No patients discontinued therapy due to an adverse event. The most common adverse events were fatigue, dizziness and headache, and two grade 3/4 laboratory abnormalities were reported.

Gilead today also announced interim results from a second Phase 2 trial (QUANTUM) examining a 12- and 24-week duration of GS-7977 plus RBV in treatment-naive patients. Twenty-five patients were randomized to the 12-week treatment arm: 19 genotype 1 patients; four genotype 3 patients; and two genotype 2 patients. Two genotype 1 patients discontinued therapy prematurely during the 12-week treatment period. At the four-week post-treatment time period, data were available for 17 genotype 1 patients. Of these, 10/17 (59 percent) remained HCV RNA undetectable. Seven patients (41 percent) experienced viral relapse. Additionally, seven of the patients who have reached the eight week post-treatment time period, and who achieved SVR4, remain HCV RNA undetectable.

The overall safety and efficacy profile of GS-7977 was consistent with that seen in ELECTRON. No patients experienced viral rebound while on treatment and no patients discontinued therapy due to an adverse event.

Eleven of the 25 patients (44 percent) in ELECTRON and three of 19 patients (16 percent) in QUANTUM had the IL28B C/C genetic polymorphism. Each of the three patients who relapsed in the ELECTRON study had a different IL28B polymorphism (C/C, C/T or T/T). The seven patients who relapsed in the QUANTUM study either had IL28B C/T (n=4) or IL28B T/T (n=3) genetic polymorphisms. Patients in both studies will continue to be observed to determine sustained virologic response rates at weeks 12 and 24 of follow-up (SVR12 and SVR24).

"The early results from these studies confirm that GS-7977 has the potential to become the cornerstone of an efficacious, all-oral combination regimen for many patients with chronic hepatitis C infection," said John McHutchison, MD, Senior Vice President, Liver Disease Therapeutics, Gilead Sciences. "We look forward to more data unfolding as our trials progress and we expect to initiate additional studies with GS-7977 in combination with other oral antivirals in our pipeline in the coming months. Our goal is to develop a short, simple, safe and effective single tablet regimen for HCV patients throughout the world."

About ELECTRON

ELECTRON is an ongoing Phase 2 randomized open-label clinical study evaluating GS-7977 for the treatment of chronic HCV infection. The primary endpoint of the trial is the safety and tolerability of GS-7977 400 mg once-daily for 8 or 12 weeks, with and without RBV and/or Peg-IFN in HCV patients with genotypes 1, 2 or 3. Study populations include treatment-naive non-cirrhotic patients and those who have failed prior interferon based therapies or "null" responders.

About QUANTUM

QUANTUM is a Phase 2 randomized double-blind placebo-controlled clinical study evaluating GS-7977 for the treatment of chronic HCV infection. The current active arms of the trial are examining GS-7977 400 mg once-daily plus RBV for 12 or 24 weeks in cirrhotic and non-cirrhotic treatment-naive HCV patients with genotypes 1, 2 and 3. The results announced today are for the cohort of patients who have received and completed 12 weeks of therapy with GS-7977 plus RBV (n=25).

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the possibility that the proportion of patients who maintain a sustained virologic response 12 and 24 weeks post-treatment will not be as favorable as the sustained virologic response rates reported in this press release and the possibility of unfavorable results from additional arms of the ELECTRON and QUANTUM studies and subsequent clinical trials involving GS-7977 and RBV. As a result, GS-7977, including in combination with other oral antivirals in Gilead's pipeline, may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of the compounds if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. In addition, Gilead may be unable to develop an all-oral antiviral regimen for HCV genotype 1 patients or a pangenotypic regimen for all HCV patients. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Annual Report on Form 10-K for the year ended December 31, 2011, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

For more information on Gilead Sciences, please visit the company's website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

SOURCE: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Susan Hubbard, 650-868-5215 (Investors)
shubbard@gilead.com
Patrick O'Brien, 650-522-1936 (Investors)
pobrien@gilead.com
Cara Miller, 650-576-7849 (Media)
cmiller@gilead.com

The Street - "Winners, Losers From EASL Hep C Data Dump"

Article posted on 4-4-12 on The Street.com. The author is right - the data people really want to see (tx-naive arm of ELECTRON; QUANTUM and GS-7977 + daclatasvir) won't be available until 4-21 after the Late Breaker sessions. After all, EASL has to fill seats for five days and Barcelona isn't just up the street for most of us. These leaves room for speculation - LOTS of speculation in the case of Idenix, which saw it's market cap take a hit after an analyst speculated that because nuc mericitabine (RG7128) under-performed in the JUMP-C study, it's distant cousin IDX184 would likely do the same.  The Idenix CEO quickly retorted that such comparisons are unfounded. We'll see - amazing the power of the Wall Street analyst in this market place. 

Adam Feuerstein
04/04/12 - 03:20 PM EDT
Updated with new information, including comments from the CEO of Idenix Pharmaceuticals.

BOSTON (TheStreet) -- The European Association for the Study of the Liver (EASL) finally released hepatitis C drug research abstracts Wednesday ahead of its closely followed conference in two weeks. But investors looking for clear winners and losers in the race to develop new all-oral hepatitis therapies came away disappointed.

As with all things hepatitis C, the EASL abstract "data dump" raised more questions than provided answers, in part because a lot of the data investors most wanted to see remains under wraps.

Still, Wall Street loves to make snap judgments, so Abbott(ABT) shares rose less than 1% to $61.60 on strong results from a small mid-stage study of a three-drug, all-oral regimen, which resulted in hepatitis C cure rates greater than 90%.

Abbott's gain was Gilead Science's(GILD) pain, causing the latter's shares to fall 2% to $47.13. Further hurting Gilead Wednesday was the absence of new data on GS-7977, the hepatitis C drug acquired in the $11 billion Pharmasset purchase. EASL chose not to make GS-7977 data available Tuesday, withholding for presentation at the meeting itself.

EASL also kept under wraps data from an important study combining Bristol-Myers Squibb's(BMY) daclatasvir with Gilead's GS-7977. A Bristol spokesperson did confirm, however, that interim results tracking early cure rates from this study will be presented at the EASL meeting.

The biggest loser Wednesday appears to be Idenix Pharmaceuticals(IDIX), with shares down 12% to $8.99 but not because of any new information released on its hepatitis C drugs. Instead, investors appear to be worried about the future of Idenix's lead drug IDX184 based on poor results released today on a similar drug being developed by Roche.

EASL's International Liver Congress is being held April 18-22.

More details on the hepatitis C research abstracts made public Wednesday:

Abbott: Today's results come from a phase II study of its own all-oral Hep C regimen consisting of protease inhibitor ABT-450, a ritonavir booster and the non-nuke polymerase inhibitor ABT-333. The study enrolled treatment naive genotype 1 patients as well as treatment-experienced non-responders. Patients were treated for 12 weeks.

In the treatment-naive patients, SVR12 or hepatitis C "cure" rates were 93% and 95% for the low- and high-dose arms, respectively. These are some of the strongest cure rates seen for new hepatitis C therapies, particularly for regimens that exclude injectable interferon. The high cure rates are even more impressive given that a majority of the patients enrolled were diagnosed with the more difficult-to-treat genotype 1A subtype.

In patients who failed to respond to previous treatment, the Abbott all-oral regimen resulted in a cure rate of 47%.

One looming concern about the Abbott hepatitis C regimen is convenience. As formulated now, patients must take one pill once per day and another two pills twice per day. For a relatively short treatment duration of 12 weeks, remembering to take a total of five pills per day may not be a problem, unless competing companies develop equally effective and simpler therapies.

Idenix: A Roche study combining the nucleoside polymerase inhibitor mericitabine, a protease inhibitor danoprevir and ribavirin proved to be relatively unsuccessful, with a cure rate of 41% overall (71% in genotype 1b patients and just 26% in the harder-to-treat genotype 1a patients.)

This study has nothing to with Idenix except that the company's own nucleoside polymerase inhibitor IDX184 is perceived by some investors to be similar to that of Roche's mericitabine. This raises concerns that any future combination regimen pairing IDX184 with a protease inhibitor may result in similarly poor cure rates.

Idenix CEO Ron Renaud calls comparisons between IDX184 and mericitabine "ridiculous," adding that data already presented shows '184 to be more like GS-7977 than mericitabine. "Comparing '184 to mericitabine, I don't know where that comes from," says Renaud. "It's just conjecture and assumptions being made by some… All we can do is continue to generate good data. We remain as optimistic about '184 as we've ever been." Hepatitis C data not yet released by EASL but expected at the meeting:

Gilead Sciences: Data from two separate but similar studies (ELECTRON and QUANTUM), both involving the two-drug combination of GS-7977 plus ribavirin in treatment-naive genotype 1 patients.

Gilead has said results from the QUANTUM study could be announced in a press release early in the second quarter i.e. before the start of the EASL meeting. Investors are sure to scour the EASL web site Thursday for any early patient data that may give a hint about the later '7977 results. Much is riding on the outcomes from these treatment-naive patient studies because '7977's potency was cast in doubt due to poor results in so-called "null responder" patients.

Bristol-Myers Squibb: Interim results from a phase II study combining Bristol's NS5a inhibitor daclatasvir (BMS-52) with Gilead's GS-7977 in genotypes 1, 2, and 3 is the most highly anticipated data presentation at the EASL meeting this year. The study is important because it will be one of the first glimpses at the Hep C-killing potency of these two classes of direct-acting antivirals combined into a single, all-oral therapy.

If this study is successful, Bristol is expected to swap out GS-7977 for its newly acquired nuke INX-189, gained from the Inhibitex acquisition. Gilead may also capitalize on the study by combining GS-7977 with its own NS5a inhibitor.

--Written by Adam Feuerstein in Boston.