Efavirenz

December 19, 2024 6:45 am ET Trials met efficacy success criteria for non-inferiority of DOR/ISL to comparator antiretroviral therapies in adults with virologically suppressed HIV-1 Safety profiles were generally comparable between DOR/ISL and other therapies in these trials RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced topline results from two pivotal Phase 3 trials of the investigational, once-daily, oral, two-drug, single-tablet regimen of doravirine/islatravir [DOR/ISL (100 mg/0.25 mg)] in adults with HIV-1 infection that is virologically suppressed on different antiretroviral therapy regimens [baseline antiretroviral therapy (bART)]; MK-8591A-051 or bictegravir/emtricitabine/tenofovir alafenamide i [BIC/FTC/TAF (50 mg/200 mg/25 mg)]; MK-8591A-052 . The success criterion for the primary efficacy hypothesis, as measured by the percentage of participants with HIV-1 RNA levels ≥50 copies/mL at Week 48, was met in both trials. DOR/ISL was demonstrated to be non-inferior to bART in open-label trial MK-8591A-051 and non-inferior to BIC/FTC/TAF in double-blind trial MK-8591A-052. The superiority criteria were not met in trial MK-8591A-052. Primary safety objectives of both trials were also met. The company is planning to present detailed findings from these trials at a future scientific congress and will also plan to file these data with regulatory authorities. In the U.S., doravirine is approved for the treatment of adults with HIV-1 in combination with other antiretrovirals, as a single agent (PIFELTRO) and a component of a single-tablet regimen [DELSTRIGO; doravirine, lamivudine, and tenofovir disoproxil fumarate (DOR/3TC/TDF)]. “We are encouraged by the results from these Phase 3 trials evaluating a once-daily, oral, two-drug, single-tablet regimen of doravirine and islatravir,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “We are committed to advancing our clinical programs for islatravir in combination with other antiretrovirals as potential options to help address the needs of people living with HIV.” Islatravir (MK-8591), Merck’s investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI), exhibits both transcriptase and translocation inhibition (which prevents nucleotide binding and incorporation to the DNA chain, resulting in immediate chain termination) and delayed chain termination (which prevents nucleotide incorporation even in the event of translocation). Islatravir is being evaluated in multiple early and late-stage clinical trials in combination with other antiretroviral therapies for the treatment of HIV-1. In addition to the MK-8591A-051 and MK-8591A-052 trials, ongoing Phase 3 trials of DOR/ISL include MK-8591A-053 in people with HIV who had not previously received treatment (treatment-naïve), and MK-8591A-054 evaluating open-label DOR/ISL (100 mg/0.25 mg) in individuals who participated in earlier Phase 3 trials of DOR/ISL (100 mg/0.75 mg). About MK-8591A-051 ( NCT05631093 ) MK-8591A-051 is a Phase 3, randomized, active-controlled, open-label clinical trial evaluating a switch to investigational, oral, once-daily DOR/ISL (100 mg/0.25 mg) in adults with HIV-1 infection that has been virologically suppressed using ART. Participants (n=551) were randomized 2:1 to either switch to investigational DOR/ISL or continue with their current bART regimen through Week 48. After Week 48, all participants receive DOR/ISL through Week 144 of the trial. After Week 144, eligible participants may continue on DOR/ISL and continue trial treatment until Week 240 or when DOR/ISL becomes commercially accessible (whichever comes first). The primary efficacy (percentage of participants with HIV-1 RNA levels ≥50 copies/mL) and safety (number of participants experiencing adverse events (AEs) and discontinuing trial intervention due to AEs) endpoints were assessed at Week 48. About MK-8591A-052 ( NCT05630755 ) MK-8591A-052 is a Phase 3, randomized, active-controlled, double-blind clinical trial evaluating a switch to investigational, oral, once-daily DOR/ISL (100mg /0.25mg) in adults with HIV-1 infection that has been virologically suppressed using BIC/FTC/TAF (50 mg/200 mg/25 mg). Participants (n=513) were randomized 2:1 to either switch to DOR/ISL or continue on BIC/FTC/TAF through Week 144. After Week 144, eligible participants may continue on DOR/ISL and continue trial treatment until Week 240 or when DOR/ISL becomes commercially accessible (whichever comes first). The primary efficacy (percentage of participants with HIV-1 RNA levels ≥50 copies/mL) and safety (number of participants experiencing AEs and discontinuing trial intervention due to AEs) endpoints were assessed at Week 48. Indications and usage for PIFELTRO and DELSTRIGO in the U.S. PIFELTRO is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine. DELSTRIGO is indicated as a complete regimen for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of DELSTRIGO. Selected Safety Information Warning: Posttreatment Acute Exacerbation of Hepatitis B (HBV) All patients with HIV-1 should be tested for the presence of HBV before initiating ARV therapy. Severe acute exacerbations of HBV have been reported in people with concomitant HIV-1 and HBV who have discontinued products containing lamivudine or tenofovir disoproxil fumarate (TDF), which are components of DELSTRIGO. Patients coinfected with HIV-1 and HBV who discontinue DELSTRIGO should be monitored with both clinical and laboratory follow-up for at least several months after stopping DELSTRIGO. If appropriate, initiation of anti-HBV therapy may be warranted. Contraindications PIFELTRO and DELSTRIGO are contraindicated when coadministered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers (including the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent mitotane; and the herbal product St. John’s wort (Hypericum perforatum)), as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of DELSTRIGO and PIFELTRO. DELSTRIGO is contraindicated in patients with a previous hypersensitivity reaction to lamivudine. Warnings and Precautions Severe Skin Reactions Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during the postmarketing experience with doravirine-containing regimens. Discontinue PIFELTRO or DELSTRIGO, and other medications known to be associated with severe skin reactions, immediately if a painful rash with mucosal involvement or a progressive severe rash develops. Clinical status should be closely monitored, and appropriate therapy should be initiated. New or Worsening Renal Impairment Renal impairment, including cases of acute renal failure and Fanconi syndrome, have been reported with the use of TDF. DELSTRIGO should be avoided with concurrent or recent use of a nephrotoxic agent (eg, high-dose or multiple NSAIDs). Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in people living with HIV with risk factors for renal dysfunction who appeared stable on TDF. Prior to or when initiating DELSTRIGO, and during treatment, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue DELSTRIGO in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Discontinue DELSTRIGO if estimated creatinine clearance declines below 50 mL/min. Bone Loss and Mineralization Defects In clinical trials in adults living with HIV, TDF was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher. Cases of osteomalacia associated with proximal renal tubulopathy have been reported with the use of TDF. Immune Reconstitution Syndrome Immune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment. Drug Interactions Because DELSTRIGO is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. Coadministration of PIFELTRO with efavirenz, etravirine, or nevirapine is not recommended. If DELSTRIGO is coadministered with rifabutin, take one tablet of DELSTRIGO once daily, followed by one tablet of doravirine (PIFELTRO) approximately 12 hours after the dose of DELSTRIGO. If PIFELTRO is coadministered with rifabutin, increase PIFELTRO dosage to one tablet twice daily (approximately 12 hours apart). Consult the full Prescribing Information prior to and during treatment for more information on potential drug-drug interactions. Dosage and Administration/Specific Populations Renal Impairment Because DELSTRIGO is a fixed-dose combination tablet and the dosage of lamivudine and TDF cannot be adjusted, DELSTRIGO is not recommended in patients with estimated creatinine clearance less than 50 mL/min. Adverse Reactions The most common adverse reactions with DELSTRIGO (incidence ≥5%, all intensities) were dizziness (7%), nausea (5%), and abnormal dreams (5%). The most common adverse reactions with PIFELTRO (incidence ≥5%, all intensities) were nausea (7%), dizziness (7%), headache (6%), fatigue (6%), diarrhea (6%), abdominal pain (5%), and abnormal dreams (5%). By week 96 in DRIVE-FORWARD, 2% of adult participants in the PIFELTRO group and 3% in the darunavir+ritonavir (DRV+r) group had adverse events leading to discontinuation of study medication. By week 96 in DRIVE-AHEAD, 3% of adult participants in the DELSTRIGO group and 7% in the efavirenz (EFV)/emtricitabine (FTC)/TDF group had adverse events leading to discontinuation of study medication. In DRIVE-FORWARD, mean changes from baseline at week 48 in LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C) were pre-specified. LDL-C: -4.6 mg/dL in the PIFELTRO group vs 9.5 mg/dL in the DRV+r group. Non-HDL-C: -5.4 mg/dL in the PIFELTRO group vs 13.7 mg/dL in the DRV+r group. The clinical benefits of these findings have not been demonstrated. In DRIVE-AHEAD, mean changes from baseline at week 48 in LDL-C and non-HDL-C were pre-specified. LDL-C: -2.1 mg/dL in the DELSTRIGO group vs 8.3 mg/dL in the EFV/FTC/TDF group. Non-HDL-C: -4.1 mg/dL in the DELSTRIGO group vs 12.7 mg/dL in the EFV/FTC/TDF group. The clinical benefits of these findings have not been demonstrated. In DRIVE-SHIFT, mean changes from baseline at week 24 in LDL-C and non-HDL-C were pre-specified. LDL-C: -16.3 mg/dL in the DELSTRIGO group vs -2.6 mg/dL in the PI + ritonavir group. Non-HDL-C: -24.8 mg/dL in the DELSTRIGO group vs -2.1 mg/dL in the PI + ritonavir group. The clinical benefits of these findings have not been demonstrated. In DRIVE-AHEAD, neuropsychiatric adverse events were reported in the three pre-specified categories of sleep disorders and disturbances, dizziness, and altered sensorium. Twelve percent of adult participants in the DELSTRIGO group and 26% in the EFV/FTC/TDF group reported neuropsychiatric adverse events of sleep disorders and disturbances; 9% in the DELSTRIGO group and 37% in the EFV/FTC/TDF group reported dizziness; and 4% in the DELSTRIGO group and 8% in the EFV/FTC/TDF group reported altered sensorium. The safety of DELSTRIGO in virologically-suppressed adults was based on week 48 data from participants in the DRIVE-SHIFT trial. Overall, the safety profile in virologically-suppressed adult participants was similar to that in participants with no ARV treatment history. Serum ALT and AST Elevations: In the DRIVE-SHIFT trial, 22% and 16% of participants in the immediate switch group experienced ALT and AST elevations greater than 1.25 X ULN, respectively, through 48 weeks on DELSTRIGO. For these ALT and AST elevations, no apparent patterns with regard to time to onset relative to switch were observed. One percent of participants had ALT or AST elevations greater than 5 X ULN through 48 weeks on DELSTRIGO. The ALT and AST elevations were generally asymptomatic, and not associated with bilirubin elevations. In comparison, 4% and 4% of participants in the delayed switch group experienced ALT and AST elevations of greater than 1.25 X ULN through 24 weeks on their baseline regimen. Pregnancy/Breastfeeding There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PIFELTRO or DELSTRIGO during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Inform individuals with HIV-1 infection of the potential risks of breastfeeding, including: (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV-1–positive infants), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults. About Islatravir (MK-8591) and Merck’s HIV Research Islatravir (MK-8591) is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) under evaluation in multiple ongoing early and late-stage clinical studies in combination with other antiretrovirals for the treatment of HIV-1. Studies with islatravir are designed to offer different dosing options as potential daily and once-weekly treatments. For an overview of Merck’s HIV treatment and prevention clinical development program, please click here . Merck’s Commitment to HIV For more than 35 years, Merck has been committed to scientific research and discovery in HIV leading to scientific breakthroughs that have helped change HIV treatment. Our work has been pioneering in the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV, with the goal of reducing the growing burden of infection worldwide. We want to ensure people are not defined by HIV and our work focuses on transformational innovations, collaborations with others in the global HIV community, and access initiatives aimed at the goal of helping to end the HIV epidemic for everyone. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2023, and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( www.sec.gov ). Please see Prescribing Information for PIFELTRO (doravirine) at: https://www.merck.com/product/usa/pi_circulars/p/pifeltro/pifeltro_pi.pdf and Patient Information for PIFELTRO (doravirine) at: https://www.merck.com/product/usa/pi_circulars/p/pifeltro/pifeltro_ppi.pdf Please see Prescribing Information for DELSTRIGO (doravirine, lamivudine, and tenofovir disoproxil fumarate) at: https://www.merck.com/product/usa/pi_circulars/d/delstrigo/delstrigo_pi.pdf and Patient Information for DELSTRIGO (doravirine, lamivudine, and tenofovir disoproxil fumarate) https://www.merck.com/product/usa/pi_circulars/d/delstrigo/delstrigo_ppi.pdf i bictegravir/emtricitabine/tenofovir alafenamide (BIKTARVY) is a registered trademark of Gilead Sciences, Inc. Media Contacts: Julie Cunningham (617) 519-6264 Deb Wambold (215) 779-2234 Investor Contacts: Peter Dannenbaum (732) 594-1579 Steven Graziano (732) 594-1583 Source: Merck & Co., Inc.

REDWOOD CITY, Calif.--( BUSINESS WIRE )--Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic and neurologic disorders by modulating the effects of the hormone cortisol, today announced that the primary endpoint was met in the treatment phase of CATALYST, a randomized, double-blind, placebo-controlled study of Korlym ® in patients with hypercortisolism (Cushing’s syndrome) and difficult-to-control type 2 diabetes. CATALYST is a prospective, Phase 4 study with two parts. The first part assessed the prevalence of hypercortisolism by screening 1057 patients with difficult-to-control type 2 diabetes, defined as hemoglobin A1c greater than 7.5 percent despite receiving optimal therapies, including GLP-1 agonists. Of these patients, 23.8 percent were identified as having hypercortisolism and were eligible to enter CATALYST’s treatment phase, in which 136 patients were randomized, 2:1, to receive either Korlym or placebo for 24 weeks. The primary endpoint was the reduction in hemoglobin A1c between these groups. CATALYST met its primary endpoint. Patients who received Korlym exhibited a clinically meaningful and statistically significant improvement in hemoglobin A1c, with a decrease from baseline of 1.47 percent as compared to a decrease of 0.15 percent in patients who received placebo (placebo-adjusted reduction of 1.32 percent; p-value: < 0.0001). The safety profile of Korlym in this study was consistent with the medication’s label and no new side effects or adverse events were identified. Complete results from CATALYST will be presented at a medical conference next year. “CATALYST’s first part showed that hypercortisolism is much more common than previously assumed. The results announced today show that Korlym is a safe and effective treatment option,” said Ralph DeFronzo, MD, chief of the Diabetes Division and professor of medicine at UT Health San Antonio and CATALYST study investigator. “Reductions in hemoglobin A1c of this magnitude are of great clinical benefit. They are particularly compelling, given that the patients in CATALYST had been receiving our best therapies – but continued to experience serious disease. These findings should prompt expanded screening for hypercortisolism, more effective treatment and better health outcomes for patients who are struggling today.” “The results of the CATALYST study will enable physicians to more accurately diagnose and treat patients with hypercortisolism - a serious and deadly disease,” said Bill Guyer, PharmD, Corcept’s Chief Development Officer. “One in four patients with difficult-to-control type 2 diabetes have hypercortisolism and Korlym, a cortisol modulator, was highly effective in controlling hyperglycemia in this patient population.” About Hypercortisolism (Cushing’s Syndrome) Hypercortisolism is caused by excessive activity of the hormone cortisol. Symptoms vary, but most patients experience one or more of the following manifestations: hypertension, central obesity, elevated blood sugar and difficult-to-control type 2 diabetes, severe fatigue and weak muscles. Irritability, anxiety, depression and cognitive disturbances are common. Hypercortisolism can affect every organ system and can be lethal if not treated effectively. Important information about Korlym follows, and full Prescribing Information, including BOXED WARNING , and a Medication Guide are available at www.korlym.com . IMPORTANT SAFETY INFORMATION INDICATIONS AND USAGE Korlym (mifepristone) is a cortisol receptor blocker indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing’s syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery. IMPORTANT LIMITATIONS OF USE Do not use for the treatment of type 2 diabetes mellitus unrelated to endogenous Cushing’s syndrome. BOXED WARNING: TERMINATION OF PREGNANCY Mifepristone is a potent antagonist of progesterone and cortisol via the progesterone and glucocorticoid (GR-II) receptors, respectively. The antiprogestational effects will result in the termination of pregnancy. Pregnancy must therefore be excluded before the initiation of treatment with Korlym and prevented during treatment and for one month after stopping treatment by the use of a nonhormonal medically acceptable method of contraception unless the patient has had a surgical sterilization, in which case no additional contraception is needed. Pregnancy must also be excluded if treatment is interrupted for more than 14 days in females of reproductive potential. DOSAGE AND ADMINISTRATION Obtain a negative pregnancy test prior to initiating treatment with Korlym in females of reproductive potential, or if treatment is interrupted for more than 14 days. Administer once daily orally with a meal. The recommended starting dose is 300 mg once daily. Renal impairment: Do not exceed 600 mg once daily. Mild-to-moderate hepatic impairment: Do not exceed 600 mg once daily. Do not use in severe hepatic impairment. Based on clinical response and tolerability, the dose may be increased in 300-mg increments to a maximum of 1200 mg once daily. Do not exceed 20 mg/kg per day. Concomitant use of Korlym with a strong CYP3A inhibitor resulted in a 38% increase in mean plasma concentration of mifepristone. For patients already being treated with a strong CYP3A inhibitor, start with a Korlym dose of 300 mg per day and titrate to a maximum of 900 mg per day if clinically indicated. When a strong CYP3A inhibitor is administered to patients already receiving Korlym, adjust the dose as follows: for patients receiving a daily dose of 600 mg, reduce dose to 300 mg. For patients receiving a daily dose of 900 mg, reduce dose to 600 mg. For patients receiving a daily dose of 1200 mg, reduce dose to 900 mg. Titrate if clinically indicated and do not exceed a Korlym dose of 900 mg in combination with a strong CYP3A inhibitor. CONTRAINDICATIONS Pregnancy; patients taking simvastatin or lovastatin and CYP3A substrates with narrow therapeutic ranges; patients receiving systemic corticosteroids for lifesaving purposes; women with a history of unexplained vaginal bleeding or endometrial hyperplasia with atypia or endometrial carcinoma; patients with known hypersensitivity to mifepristone or to any of the product components. WARNINGS AND PRECAUTIONS Adrenal insufficiency: Patients should be closely monitored for signs and symptoms of adrenal insufficiency. Hypokalemia: Hypokalemia should be corrected prior to treatment and monitored for during treatment. Vaginal bleeding and endometrial changes: Women may experience endometrial thickening or unexpected vaginal bleeding. Use with caution if the patient also has a hemorrhagic disorder or is on anticoagulant therapy. QT interval prolongation: Avoid use with QT interval-prolonging drugs, or in patients with potassium channel variants resulting in a long QT interval. Use of strong CYP3A inhibitors: Concomitant use increases mifepristone plasma levels. Adjust Korlym dose as described in Dosage and Administration . Use only when necessary and do not exceed a Korlym dose of 900 mg. ADVERSE REACTIONS Most common adverse reactions in Cushing’s syndrome (≥20%): nausea, fatigue, headache, decreased blood potassium, arthralgia, vomiting, peripheral edema, hypertension, dizziness, decreased appetite, endometrial hypertrophy. DRUG INTERACTIONS Drugs metabolized by CYP3A: Administer drugs that are metabolized by CYP3A at the lowest dose when used with Korlym. CYP3A inhibitors: Caution should be used when Korlym is used with strong CYP3A inhibitors. Adjust Korlym dose as described in Dosage and Administration . Use only when necessary, and do not exceed a Korlym dose of 900 mg. CYP3A inducers: Do not use Korlym with CYP3A inducers. Drugs metabolized by CYP2C8/2C9: Use the lowest dose of CYP2C8/2C9 substrates when used with Korlym. Drugs metabolized by CYP2B6: Use of Korlym should be done with caution with bupropion and efavirenz. Hormonal contraceptives: Do not use with Korlym. USE IN SPECIFIC POPULATIONS Lactation: Mifepristone is present in human milk, however, there are no data on the amount of mifepristone in human milk, the effects on the breastfed infant, or the effects on milk production during long term use of mifepristone. About Corcept Therapeutics For over 25 years, Corcept’s focus on cortisol modulation and its potential to treat patients with a wide variety of serious disorders has led to the discovery of more than 1,000 proprietary selective cortisol modulators. Corcept is conducting advanced clinical trials in patients with hypercortisolism, solid tumors, ALS and liver disease. In February 2012, the company introduced Korlym, the first medication approved by the U.S. Food and Drug Administration for the treatment of patients with endogenous hypercortisolism. Corcept is headquartered in Redwood City, California. For more information, visit Corcept.com. Forward-Looking Statements Statements in this press release, other than statements of historical fact, are forward-looking statements based on our current plans and expectations and are subject to risks and uncertainties that might cause our actual results to differ materially from those such statements express or imply. These risks and uncertainties are set forth in our SEC filings, which are available at our website and the SEC’s website. In this press release, forward-looking statements include those concerning the full results of CATALYST and the date and manner of their publication; changes in medical practice, including in the frequency and clinical outcome of screening patients for hypercortisolism; the adoption of Korlym as a treatment for patients with hypercortisolism and difficult-to-control diabetes; and Korlym’s commercial prospects. We disclaim any intention or duty to update forward-looking statements made in this press release.