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– SPIRIT Study Meets 24-Week Primary Endpoint of Non-Inferiority –
WASHINGTON--(BUSINESS WIRE)--Jul. 24, 2012-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced 24-week data from a Phase 3 clinical trial, SPIRIT (Switching boosted PI to Rilpivirine In Combination with Truvada as a Single Tablet Regimen), which evaluated virologically suppressed treatment-experienced HIV patients switching from a multi-pill regimen containing a ritonavir-boosted protease inhibitor to the once-daily single tablet regimen Complera® (emtricitabine/rilpivirine/tenofovir disoproxil fumarate). The study met its 24-week primary endpoint, which found that switching to Complera was non-inferior to remaining on a ritonavir-boosted protease inhibitor regimen. These findings will be presented today in an oral session (Abstract #TUAB0104) at the 19th International AIDS Conference (AIDS 2012) in Washington, D.C.
“Since its approval last year for patients new to HIV therapy, the daily single tablet regimen of Complera has become an important addition to the list of treatment options available for these patients,” said Frank J. Palella Jr., MD, Professor of Medicine at the Northwestern University Feinberg School of Medicine and Principal Investigator of the SPIRIT study. “In this current study, data demonstrate Complera has the potential to help a broader range of HIV-infected patients.”
Complera was approved by the U.S. Food and Drug Administration (FDA) in August 2011 for treatment-naïve patients, and is the latest complete HIV regimen available in a once-daily single tablet. The product combines Gilead’s Truvada® (emtricitabine and tenofovir disoproxil fumarate), which itself is a fixed-dose combination of two HIV medicines, with Janssen R&D Ireland’s rilpivirine (marketed as Edurant®).
At 24 weeks of treatment, 94 percent of patients (n=297/317) who switched to Complera maintained HIV RNA (viral load) levels less than 50 copies/mL compared to 90 percent of patients (n=143/159) who remained on a regimen containing a ritonavir-boosted protease inhibitor-based regimen (FDA snapshot algorithm; 95 percent CI for the difference: -1.6 percent to +9.1 percent; predefined criterion for non-inferiority was the lower bound of a two sided 95 percent CI of -12 percent). Fewer patients taking Complera experienced virologic failure compared to those taking a protease-based regimen (0.9 percent versus 5 percent, respectively). Additionally, patients in the Complera arm demonstrated statistically significant improvements in total cholesterol levels. The ratio of total cholesterol to HDL (high-density lipoprotein or “good” cholesterol) declined by an average of 0.27 in the Complera arm, compared to an increase of 0.08 in the protease inhibitor arm (p<0.001).
In addition to SPIRIT, Gilead is evaluating Complera in two post-marketing studies - an open-label Phase 3b head-to-head trial comparing Complera to Atripla® (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) among patients who are new to therapy (Study 110), and a Phase 2b open-label pilot study evaluating the efficacy and safety of switching virologically suppressed Atripla patients to Complera (Study 111). Twenty-four week data from Study 111 were presented at the 18th Annual Conference of the British HIV Association (BHIVA) in April 2012, and 48-week data will be presented at an upcoming medical meeting.
SPIRIT Study
SPIRIT (Study 106) is a randomized (2:1), open-label Phase 3 study of switching virologically suppressed HIV patients from a regimen consisting of a ritonavir-boosted protease inhibitor and two nucleoside reverse transcriptase inhibitors (n=159) to Complera (n=317). The primary objective of the study is to evaluate the non-inferiority, at a 12 percent margin, of Complera compared to a protease-based regimen in maintaining HIV RNA levels less than 50 copies/mL through 24 weeks of therapy, based on the FDA snapshot algorithm. Secondary endpoints include changes in serum lipid levels, change in CD4 cell count, and safety and tolerability through 48 weeks of therapy. Patients randomized to the protease-based regimens rolled over to Complera after week 24.
At baseline, patients in the Complera switch arm had mean CD4 cell counts of 576 cells/mm3 compared to 600 cells/mm3 in the protease arm. Mean fasting lipids levels at baseline for the Complera and protease arms, respectively, were 192 and 194 mg/dL in total cholesterol, 121 and 124 mg/dL in LDL, 53 and 50 mg/dL in HDL, and 163 and 173 mg/dL in triglycerides. Mean ratios of total cholesterol to HDL at baseline were 3.86 for the Complera arm and 4.08 for the protease arm.
Virologic Outcome at 24 Weeks (FDA Snapshot Algorithm)
n=317
Protease-Based Regimen
n=159
Missing data during 24-week window but on study drug
Changes in CD4 cell counts at 24 weeks of therapy were +20 cells/mm3 for the Complera arm and +32 cells/mm3 for the protease-based regimen (p=0.28). Five percent (n=16) and 6.9 percent (n=11) of patients in the Complera and protease-based regimen arms, respectively, experienced a Grade 3 or 4 adverse event.
At 24 weeks Complera patients had greater mean changes in fasting total cholesterol (-25 vs. -1 mg/dL), LDL (-16 vs. 0 mg/dL) and triglycerides (-53 vs. +3 mg/dL) compared to those who remained on protease-based regimens (p<0.001 for all comparisons between treatment groups). Patients in both arms had similar changes in HDL (-4 vs. -1 mg/dL for Complera and protease-based regimen, respectively; p<0.001). Switching to Complera resulted in greater improvements in the 10-year Framingham Risk Score, a measure of cardiovascular risk, at week 24 compared to a protease-based regimen (p=0.001).
The mean change in estimated glomerular filtration rate (GFR) by Cockcroft-Gault at week 24 was -4.4 mL/min for the Complera arm and 0.1 mL/min for the protease-based regimen (p<0.001). Resistance mutations were observed in two patients in the Complera switch arm and one in the protease inhibitor arm.
Complera Important Product Safety Information and Indication
WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate, a component of Complera, in combination with other antiretrovirals.
Complera is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of Complera have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued Emtriva or Viread, which are components of Complera. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue Complera. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
CONTRAINDICATIONS
Complera should not be co-administered with the following drugs, as significant decreases in rilpivirine plasma concentrations may occur due to CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance to Complera or to the class of NNRTIs:
WARNINGS AND PRECAUTIONS
ADVERSE REACTIONS
The most common adverse drug reactions to rilpivirine (incidence greater than or equal to 2%, Grades 2-4) were insomnia and headache.
The most common adverse drug reactions to emtricitabine and tenofovir disoproxil fumarate (incidence ≥ 10%) were diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash.
DRUG INTERACTIONS
DOSAGE AND ADMINISTRATION
Adults: The recommended dose of Complera is one tablet taken orally once daily with a meal.
Renal Impairment: Because Complera is a fixed-dose combination, it should not be prescribed for patients requiring dose adjustment such as those with moderate or severe renal impairment (creatinine clearance below 50 mL per minute).
INDICATION
Complera is indicated for use as a complete regimen for the treatment of HIV-1 infection in antiretroviral treatment-naïve adults. This indication is based on Week 48 safety and efficacy analyses from 2 randomized, double-blind, active controlled, Phase 3 trials in treatment-naïve subjects comparing rilpivirine to efavirenz.
The following points should be considered when initiating therapy with Complera:
Complera is not recommended for patients less than 18 years of age.
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 risk that healthcare providers may not recognize the benefits of switching their patients from protease inhibitor-based regimens to Complera. In addition, as Complera is used over longer periods of time by many patients with underlying health problems taking numerous other medicines, Gilead may find new issues such as safety, resistance or drug interaction issues, which may require it to provide additional warnings or contraindications on the label or narrow Complera’s approved indication, each of which could reduce the market acceptance of Complera. 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 Quarterly Report on Form 10-Q for the quarter ended March 31, 2012, 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.
U.S. full prescribing information for Complera is available at www.Complera.com.
Complera and Truvada are registered trademarks of Gilead Sciences, Inc.
Atripla is a registered trademark of Bristol-Myers Squibb & Gilead Sciences, LLC.
Edurant is a registered trademark of Janssen R&D Ireland.
For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
Source: Gilead Sciences, Inc.
Gilead Sciences, Inc.Patrick O’Brien, 650-522-1936 (Investors)Erin Rau, 650-522-5635 (Media)