Search the Community
Showing results for tags 'korlym'.
Found 13 results
-
Corcept Therapeutics (NASDAQ:CORT) announced an agreement with Hikma Pharmaceuticals (OTCPK:HKMPF) USA on Thursday to resolve the ongoing patent lawsuit related to Korlym, an oral therapy indicated for patients with Cushing’s syndrome. The litigation was filed in the New Jersey district court in 2021, shortly after Hikma (OTCPK:HKMPF) informed Corcept (CORT) about its submission of an Abbreviated New Drug Application (ANDA) seeking FDA approval for a generic version of Korlym. Per the terms of the settlement, Corcept (CORT) has allowed Hikma (OTCPK:HKMPF) the rights to market a generic version of Korlym from Oct. 01, 2034, or earlier subject to certain conditions. The companies plan to submit the agreement for the review of the U.S. Federal Trade Commission (FTC) and the United States Department of Justice (DOJ). A similar patent lawsuit filed by Corcept (CORT) against the U.S. unit of Teva Pharmaceutical (TEVA) remains pending. Thanks mainly to higher sales volumes of Korlym, Corcept (CORT) added $366.0M net product revenue in 2021 with ~3% YoY growth. From https://seekingalpha.com/news/3915421-cort-stock-on-watch-after-patent-settlement-with-hikma-for-korlym -
Cushing’s disease is a progressive pituitary disorder in which there is an excess of cortisol in the body. While the disease can be treated surgically, this option is not possible for all patients. This is one of the approved medications that assist in controlling cortisol levels in people with Cushing’s disease. Korlym (mifepristone), developed and marketed by Corcept Therapeutics, is an FDA-approved treatment for high blood sugar (hyperglycemia) in adults with Cushing’s syndrome who have type 2 diabetes or glucose intolerance, and for whom surgery is not an option, or failed to control their symptoms. Bios of Cushies who have taken Korlym. Korlym discussions on the Message Boards. Learn more here and here. How does Korlym work? Cushing’s syndrome is characterized by high levels of cortisol in the body. Cortisol is a hormone that helps control a wide range of bodily functions, including blood pressure, salt levels, and blood sugar (glucose) levels. Too much cortisol may cause blood sugar levels to rise — a hallmark of both type 2 diabetes and glucose intolerance. Cortisol exerts its effects by binding to glucocorticoid receptors on the surface of cells. Korlym works by blocking cortisol’s access to these receptors, thereby preventing the chain of events leading to elevated blood sugar levels and diabetes. The medication is specifically meant to treat patients with endogenous Cushing’s syndrome, in which the body’s own overproduction of cortisol — usually due to the presence of a tumor — is the reason why hormone levels rise above healthy limits. Korlym in clinical trials Corcept conducted a Phase 3 trial (NCT00569582) to evaluate the safety and efficacy of mifepristone in 50 adults with endogenous Cushing’s syndrome and type 2 diabetes or impaired glucose tolerance, or high blood pressure alone. In the group with diabetes, 60% of participants showed a clinically meaningful improvement in glucose control in a two-hour oral glucose test. In the high blood pressure group, an improvement in diastolic blood pressure — the pressure in the arteries while the heart rests between beats — was seen in 38% of participants. In addition, an overall clinical improvement was seen in 87% of participants, as assessed by an independent review board. Board members looked at a range of symptoms, including body weight and composition, Cushing-like appearance, and psychological symptoms. Common adverse events reported in the study included fatigue, nausea, headache, low potassium, joint pain, vomiting, and swelling, called edema. Thickening of the lining of the uterus was reported among female participants. A pilot Phase 4 trial (NCT01990560) also demonstrated that mifepristone may be helpful in managing mild autonomous cortisol secretion (ACS), a subclinical form of Cushing’s syndrome in which patients do not display typical signs and symptoms of Cushing’s, despite having high cortisol levels. That pilot trial enrolled eight patients who received 300 mg tablets once daily for six months. In two patients, this dose was upped to 600 mg after two months due to a lack of clinical response. Treatment led to significant reductions in fasting glucose levels and insulin resistance — when certain cells no longer respond well to insulin, a hormone that controls how cells store and use glucose. Another study also indicated that mifepristone can effectively treat patients with ectopic Cushing’s syndrome. This is a form of Cushing’s caused by tumors found outside the brain’s pituitary gland, in which case the condition is known as Cushing’s disease. Other details Korlym’s blood absorption is higher when the medication is given with food. Patients should, therefore, take the medication within one hour of having a meal, so as to increase its effectiveness. Importantly, eating grapefruit or drinking grapefruit juice should be avoided while taking the medication, since both may interfere with its absorption. Korlym also may interact with a variety of other prescription meds, including cholesterol-lowering medicines simvastatin and lovastatin, the immunosuppressant cyclosporine, headache treatments ergotamine and dihydroergotamine, and opioid fentanyl. The antifungal treatment ketoconazole (sold under the brand name Nizoral, among others), used off-label to treat Cushing’s in the U.S., also can change the way Korlym is absorbed in the body. Since both medications can be prescribed simultaneously to Cushing’s patients, doctors should carefully evaluate their benefits, taking into account the potential risks. Additionally, mifepristone — Korlym’s active ingredient — blocks the action of the hormone progesterone, which is important for maintaining pregnancy. Taking Korlym during pregnancy will result in pregnancy loss. Therefore, Korlym should never be taken by women who are pregnant or by those who may become pregnant. Treatment with Korlym also may cause blood potassium levels to drop, a condition known as hypokalemia. Potassium is a mineral that helps the body regulate fluid balance, nerve signals, and muscle contraction. As such, patients’ potassium levels should be monitored closely in the first weeks after starting or increasing Korlym’s dose, as well as periodically thereafter.
-
- 1
-
-
- korlym
- mifepristone
- (and 2 more)
-
In Teva Pharmaceuticals USA, Inc. v. Corcept Therapeutics, Inc.,1 the Federal Circuit affirmed the obviousness analysis performed by the Patent Trial and Appeal Board (“PTAB”), which found that Corcept’s patent for methods of treating Cushing’s disease by co-administering two different types of drugs with a specific range of dosing amounts was not obvious—even where the prior art directed one to combine the two—because there was no reasonable expectation of success for the specific dose claimed in the patent. Background The patent relates to methods for treating Cushing’s syndrome by co-administering mifepristone and a strong CYP3A inhibitor. Cushing’s syndrome is a metabolic disorder caused by excess cortisol.,2 Mifepristone was recognized in the prior art as a potential treatment for Cushing’s syndrome in the 1980’s.,3 Decades later, Corcept sponsored the first major clinical trial of mifepristone in patients with Cushing’s syndrome, in which participants were dosed with 300 to 1200 mg per day of mifepristone. Thereafter, Corcept filed a New Drug Application (“NDA”) with the U.S. Food and Drug Administration (“FDA”) to seek marketing approval for Korlym®, a 300 mg mifepristone tablet to control “hypercalcemia secondary to hypercortisolism” in patients with Cushing’s syndrome.,4 The FDA approved the NDA, including the prescribing information contained in the label.5 The label “recommended [a] starting dose [of] 300 mg once daily” and allowed for a dosage increase “in 300 mg increments to a maximum of 1200 mg once daily.”6 The label specifically warned against using mifepristone “with strong CYP3A inhibitors” and limited the dose to “300 mg per day when used with strong CYP3A inhibitors.”7 However, when it approved the NDA, the FDA issued several post market requirements, one of which was that Corcept must conduct a drug-drug interaction study with mifepristone and a strong CYP3A inhibitor.8 A memo from the Office of Clinical Pharmacology was provided to Corcept by the FDA (“the Lee memo”), which explained that “[t]he degree of change in exposure of mifepristone when co-administered with strong CYP3A inhibitors is unknown” and “may present a safety risk.”9 The concern was that without the required study the patients with Cushing’s syndrome that take strong inhibitors may be unable to use mifepristone.10 Corcept conducted the study requested in the Lee memo.11 Based on the resulting data, Corcept sought a patent claiming a method of treating Cushing’s syndrome by co-administering mifepristone and a strong CYP3A4 inhibitor, which is the patent at issue here.12 Claim 1, which is representative of the claims, reads: A method of treating Cushing’s syndrome in a patient who is taking an original once-daily dose of 1200 mg or 900 mg per day of mifepristone, comprising the steps of: reducing the original once-daily dose to an adjusted once-daily dose of 600 mg mifepristone, administering the adjusted once-daily dose of 600 mg mifepristone and a strong CYP3A inhibitor to the patient, wherein said strong CYP3A inhibitor is selected from the group consisting of ketoconazole, itraconazole, nefazodone, ritonavir, nelfmavir, indinavir, boceprevir, clarithromycin, conivaptan, lopinavir, posaconazole, saquinavir, telaprevir, cobicistat, troleandomycin, tipranivir, paritaprevir, and voriconazole.13 Procedural Posture In 2018 Corcept brought suit against Teva in the District of New Jersey alleging that Teva’s proposed generic infringed the patent, among others.14 Teva then sought post-grant review of the patent’s claims at the PTAB, arguing that the claims would have been obvious over the Korlym® label and the Lee memo, optionally in combination with FDA guidance on drug-drug interaction studies.15 The PTAB instituted review, “construed the claims to require safe administration of mifepristone,” and found that Teva failed to meet its burden of showing that a “skilled artisan would have had a reasonable expectation of success for safe co-administration of more than 300 mg of mifepristone with a strong CYP3A inhibitor.”16 Thus, the PTAB concluded that Teva failed to prove obviousness.17 Teva’s Arguments on Appeal Teva argued to the Federal Circuit that the PTAB committed two legal errors in finding that Teva did not prove obviousness: (1) it “required precise predictability, rather than a reasonable expectation of success in achieving the claimed invention,” and (2) it found that Teva “failed to prove the general working conditions disclosed in the prior art encompassed the claimed invention” instead of applying the Federal Circuit’s “prior-art-range precedents.”18 The Federal Circuit Panel, consisting of Chief Judge Moore and Judges Newman and Reyna, rejected both of Teva’s arguments.19 The Panel determined that the PTAB “did not err by requiring Teva to show a reasonable expectation of success for a specific mifepristone dosage.” In discussing the proper standard for evaluating a reasonable expectation of success, the Panel cited prior Federal Circuit decisions explaining that the analysis “must be tied to the scope of the claimed invention.”20 It noted that because the claims of the patent require administration of a specific dosage of mifepristone, the PTAB was required to frame its analysis around that specific dosage.21 The Panel emphasized that Teva was not “required to prove a skilled artisan would have precisely predicted safe co-administration of 600 mg of mifepristone” because “[a]bsolute predictability is not required.”22 Teva was, however, required “to prove a reasonable expectation of success in achieving the specific invention claimed, a 600 mg dosage.”23 The Panel explained that the PTAB found that Teva failed to prove a reasonable expectation of success.24 Based on the prior art, a skilled artisan would not have reasonably “expected co-administration of more than 300 mg of mifepristone with strong CYP3A inhibitor to be a safe treatment of Cushing’s syndrome or related symptoms in patients.”25 Moreover, the PTAB found that a skilled artisan “would have had no expectation as to whether co-administering dosages of mifepristone above the 300 mg/day threshold” would be successful.26 Thus, because there was no expectation of success for any dosage over 300 mg, the PTAB concluded that there could not have been an expectation of success for the specific dosage of 600 mg per day.27 The Panel found that this analysis by the PTAB was correct under Federal Circuit precedent, and that “[n]othing about this analysis required precise predictability, only a reasonable expectation of success tied to the claimed invention.”28 The Panel decided that the PTAB did not err in finding that “the prior art ranges do not overlap with the claimed range” The Panel next considered the applicability of the Federal Circuit’s precedent concerning claimed ranges that overlap with those disclosed in the prior art.29 The PTAB refused to apply that line of cases, finding that “Teva had failed to prove the general working conditions disclosed in the prior art encompass the claimed invention.”30 The Panel noted a Federal Circuit decision that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.”31 In other words, “a prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.”32 “But overlap is not strictly necessary for a conclusion of obviousness” and can exist even where the ranges are “close enough” that a skilled artisan would expect them to exhibit similar properties.33 Here, the Panel explained that “[s]ubstantial evidence supports the [PTAB’s] finding that the general working conditions disclosed in the prior art did not encompass the claimed invention, i.e., there was no overlap in ranges.”34 The Korlym® label warned against taking mifepristone with a strong CYP3A inhibitor altogether, and stated that anyone nonetheless combining the two should take a maximum of 300 mg/day of mifepristone.35 This 300 mg/day cap was also repeated in other industry publications.36 The PTAB found that “the prior art capped the range of co-administration dosages at 300 mg per day.”37 The Panel agreed with this finding, concluding that the claimed range was not disclosed in the prior art.38 Teva attempted to argue that the claimed range overlaps with monotherapy dosages—which were dosages of mifepristone alone—in the prior art.39 However, because “monotherapy dosages alone cannot create an overlap with the claimed range, which is limited to co-administering mifepristone with a strong CYP3A inhibitor,” the PTAB had to determine “whether a skilled artisan would have expected “monotherapy and co-administration dosages to behave similarly.”40 As the Panel had already concluded in its reasonable expectation of success analysis, a “skilled artisan would have no such expectation.”41 Conclusion Although Teva argued that this was an “uncommonly clear-cut obviousness case” where the prior art discloses “the problem, . . . the solution, . . . and the way to find the solution,” the Panel disagreed, explaining that: “At best, the prior art directed a skilled artisan to try combing the Korlym Label, Lee, and the FDA guidance. But without showing a reasonable expectation of success, Teva did not prove obviousness.”42 Thus, the Panel’s decision helps to clarify that evaluating obviousness based on ranges disclosed in the prior art is a fact-specific analysis, in which bright lines should not be drawn. 1 Teva Pharm. USA, Inc. v. Corcept Therapeutics, Inc., No. 21-1360, slip op. (Fed. Cir. Dec. 7, 2021). 2 Id. at 2. 3 Id. 4 Id. at 2-3. 5 Id. at 3. 6 Id. 7 Id. at 3-4. 8 Id. at 3. 9 Id. 10 Id. 11 Id. at 4. 12 Id. 13 Id. at 3. 14 Corcept Therapeutics, Inc. v. Teva Pharmaceuticals USA, Inc., No. 18-3632 (D.N.J.). 15 Teva Pharmaceuticals USA, Inc. v. Corcept Therapeutics, Inc., PGR2019-00048, 2020 WL 6809812 (P.T.A.B. Nov. 18, 2020) (Final Decision). 16 Id. (emphasis added). 17 Id. 18 Teva Pharm. USA, Inc. v. Corcept Therapeutics, Inc., No. 21-1360, slip op. at 5 (Fed. Cir. Dec. 7, 2021) 19 See generally id. 20 Id. at 6 (citing Allergan, Inc. v. Apotex Inc., 753 F.3d 952, 966 (Fed. Cir. 2014); Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1366 (Fed. Cir. 2016)). 21 Id. 22 Id. 23 Id. 24 Id. 25 Id. at 6-7 (citing Final Decision at *22). 26 Id. at 7. 27 Id. 28 Id. 29 Id. at 8. 30 Id. 31 Id. (citing E.I. DuPont de Nemours & Co. v. Synvina C. V., 904 F.3d 996, 1006 (Fed. Cir. 2018)). 32 Id. at 8-9. 33 Id. at 9. 34 Id. 35 Id. 36 Id. 37 Id. 38 Id. 39 Id. 40 Id. at 9-10. 41 Id. at 10. 42 Id. From https://www.jdsupra.com/legalnews/failure-to-show-a-reasonable-4662913/
-
- 1
-
-
- cyp3a inhibitor
- mifepristone
- (and 1 more)
-
-
- 1
-
-
- ketoconazole
- patient advisory board
- (and 6 more)
-
Bettye passed away due to complications of Cushing’s disease. Once she was finally diagnosed, a decision was made against surgery and Bettye was put on the cortisol-lowering medication Korlym. Though she had initially gained weight from Cushing’s disease, as many patients do, she rapidly lost weight and was admitted into hospice care soon after. Read more at https://cushingsbios.com/2017/09/28/in-memory-bettye-jean-douglas-september-28-2016/
-
MENLO PARK, Calif., Aug. 28, 2019 (GLOBE NEWSWIRE) -- Corcept Therapeutics Incorporated (NASDAQ: CORT) announced today that the United States Patent and Trademark Office has issued a Notice of Allowance for a patent covering the administration of Korlym® with food. The patent will expire in November 2032. “This patent covers an important finding of our research – that for optimal effect, Korlym must be taken with food,” said Joseph K. Belanoff, MD, Corcept’s Chief Executive Officer. “Korlym’s label instructs doctors that ‘Korlym must always be taken with a meal.’” Upon issuance, Corcept plans to list the patent, entitled “Optimizing Mifepristone Absorption” (U.S. Pat. App. 13/677,465), in the U.S. Food and Drug Administration’s Approved Drug Products with Therapeutic Equivalence Evaluations (the “Orange Book”). Korlym is currently protected by ten patents listed in the Orange Book. Hypercortisolism Hypercortisolism, often referred to as Cushing’s syndrome, is caused by excessive activity of the hormone cortisol. Endogenous Cushing’s syndrome is an orphan disease that most often affects adults aged 20-50. In the United States, an estimated 20,000 patients have Cushing’s syndrome, with about 3,000 new patients diagnosed each year. Symptoms vary, but most people with Cushing’s syndrome experience one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper-body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Hypercortisolism can affect every organ system in the body and can be lethal if not treated effectively. About Corcept Therapeutics Incorporated Corcept is a commercial-stage company engaged in the discovery and development of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of the stress hormone cortisol. Korlym® (mifepristone) was the first treatment approved by the U.S. Food and Drug Administration for patients with Cushing’s syndrome. Corcept has discovered a large portfolio of proprietary compounds, including relacorilant, exicorilant and miricorilant, that selectively modulate the effects of cortisol but not progesterone. Corcept owns extensive United States and foreign intellectual property covering the composition of its selective cortisol modulators and the use of cortisol modulators, including mifepristone, to treat a variety of serious disorders. Forward-Looking Statements Statements in this press release, other than statements of historical fact, are forward-looking statements, which are based on Corcept’s current plans and expectations and are subject to risks and uncertainties that might cause actual results to differ materially from those such statements express or imply. These risks and uncertainties include, but are not limited to, Corcept’s ability to generate sufficient revenue to fund its commercial operations and development programs; the availability of competing treatments, including generic versions of Korlym; Corcept’s ability to obtain acceptable prices or adequate insurance coverage and reimbursement for Korlym; and risks related to the development of Corcept’s product candidates, including regulatory approvals, mandates, oversight and other requirements. These and other risks are set forth in Corcept’s SEC filings, which are available at Corcept’s website and the SEC’s website. In this press release, forward-looking statements include those concerning Corcept’s plans to list the patent “Optimizing Mifepristone Absorption” in the Orange Book; Korlym’s current protection by ten patents listed in the Orange Book; and the scope and protective power of Corcept’s intellectual property. Corcept disclaims any intention or duty to update forward-looking statements made in this press release. CONTACT: Christopher S. James, MD Director, Investor Relations Corcept Therapeutics 650-684-8725 cjames@corcept.com www.corcept.com
-
Corcept Therapeutics is recruiting participants for its Phase 3 clinical trial evaluating relacorilant as a potential treatment for Cushing’s syndrome-related side effects such as high blood pressure and impaired glucose tolerance. Also, findings from the study “A Randomized-Withdrawal, Placebo-Controlled, Phase 3 Study to Assess the Efficacy and Safety of Selective Glucocorticoid Receptor Antagonist, Relacorilant, in Patients with Cushing Syndrome (GRACE Study),” were presented at the 2019 Annual Meeting of the Endocrine Society (ENDO), in New Orleans, Louisiana. In endogenous Cushing’s syndrome there is an “internal” culprit — usually a benign tumor — that makes the body produce too much of the hormone cortisol. The excessive amount of circulating cortisol can lead to serious problems, such as type 2 diabetes and high blood pressure. Relacorilant is designed to prevent the effects of excess cortisol by blocking one of its receptors, the glucocorticoid receptor. Results from a Phase 2 trial (NCT02804750) suggest that relacorilant may manage the effects of prolonged cortisol excess in Cushing’s patients faster and without the known side effects of approved medications like Korlym (mifepristone). Also, the treatment improved glucose tolerance and improved blood pressure in patients, suggesting it could be used to treat those with endogenous Cushing’s syndrome and concurrent type 2 diabetes mellitus, impaired glucose tolerance, and/or uncontrolled high blood pressure (hypertension). Corcept has now designed the GRACE Phase 3 trial (NCT03697109), a multicenter, double-blind, placebo-controlled, randomized-withdrawal study, to evaluate relacorilant’s safety and effectiveness in these patients. GRACE will be conducted in two stages. First, all patients will be given oral relacorilant each day for 22 weeks, at doses rising from 100 mg to a maximum of 400 mg. Those who complete that stage and show improvements in pre-specified parameters of glucose tolerance or hypertension will move into the second, randomized phase of the trial. Here, they will be randomly assigned to placebo or relacorilant at the same dose they received at the end of the first stage. This new round of treatment will last 12 weeks. Treatment-related adverse events (side effects) also will be assessed for up to 48 weeks (about 11 months) as a main outcome. Additional primary goals include changes in glucose tolerance and blood pressure between the end of the first and second stages of the study. Secondary objectives include identifying the proportion of patients achieving a response in glucose tolerance and high blood pressure criteria and the proportion of those who worsened at the end of the first stage, and the changes in quality of life throughout the study. Researchers plan to enroll 130 people in these U.S. cities: Indianapolis, Indiana; Metairie, Louisiana; Jackson, Mississippi; Albany, New York; Jamaica, New York; Wilmington, North Carolina; Miami, Florida; Summerville, South Carolina; El Paso, Texas; Oklahoma City, Oklahoma, and; Aurora, Colorado. More detailed information is available here. “We look forward to presenting new findings concerning cortisol modulation in patients with hypercortisolism,” Joseph K. Belanoff, MD, Corcept’s CEO, said in a press release.
-
- 1
-
-
- clinical trial
- relacorilant
- (and 4 more)
-
The glucocorticoid receptor antagonist CORT125134 is safe and has shown preliminary signs of efficacy in healthy volunteers participating in a Phase 1 trial, say researchers in England. Their study, “Assessment of Safety, Tolerability, Pharmacokinetics, and Pharmacological Effect of Orally Administered CORT125134: An Adaptive, Double-Blind, Randomized, Placebo-Controlled Phase 1 Clinical Study,” appeared in the journal Clinical Pharmacology in Drug Development.” Cortisol signaling is indirectly controlled by the glucocorticoid receptor (GR). When cortisol binds the GR, the receptor becomes activated and migrates to the nucleus, where it regulates the expression of many genes. This influences a myriad of processes, including inflammation, immune response and brain function. CORT125134, also known as relacorilant, is being developed by Corcept Therapeutics of Menlo Park, California, for Cushing’s disease patients and others who may benefit from it. The drug is a GR antagonist, blocking the receptor’s activity. In order to evaluate the safety and tolerability of CORT125134, and learn how it behaves in the body, Corcept researchers conduced a Phase 1 trial in healthy subjects. The British study, conducted at the Quotient Clinical in Nottingham, included 81 adults who received a single ascending-dose of CORT125134 or placebo, and 48 subjects who received multiple-ascending doses of the drug versus placebo. Single doses were tested in nine distinct groups. Six tested six different doses of CORT125134, one tested a 150 mg dose in subjects receiving a high-fat meal, and two groups included patients receiving prednisone (a well-known GR activator), prednisone plus Korlym (mifepristone), or prednisone plus CORT125134. Korlym is a medicine approved for Cushing’s patients with high blood sugar levels due to high cortisol in circulation. But the drug targets the progesterone receptor and is associated with side effects like pregnancy termination and irregular vaginal bleeding. Multiple doses, given for up to 14 days, were tested in four additional cohorts. Researchers observed that CORT125134 was rapidly absorbed and eliminated, presenting a suitable profile for once-daily dosing. Efficacy was determined by CORT125134’s ability to counteract the effects of prednisone. In addition, a single dose of 500 mg or multiple dosing with 250 mg had similar effects as those seen with 600 mg of Korlym — the therapeutic dose used for Cushing’s treatments. Most common treatment-related adverse events reported in the single-ascending dose part of the study were nausea, vomiting and thirst; most were mild. In those given multiple-ascending doses, adverse events included mild musculoskeletal and connective tissue disorders, as well as gastrointestinal system disorders. Multiple 500 mg doses exceeded the maximum tolerated dose, as it led to musculoskeletal symptoms that forced researchers to stop treatment. “This first-in-human study has demonstrated that CORT125134 is well tolerated following single doses up to 500 mg and repeated doses up to 250 mg once daily for 14 days,” researchers wrote. “Pharmacological activity was confirmed following the administration of a single 500-mg dose and daily administration of 250 mg.” Corcept is now enrolling participants into a Phase 2 open-label trial (NCT02804750) to evaluate CORT125134 in patients with Cushing’s syndrome. This trial is being conducted in the United States and Europe and will include 80 participants. Top-line results are expected in the first quarter of 2018. From https://cushingsdiseasenews.com/2017/10/10/phase-1-data-demonstrates-efficacy-safety-of-cort125134-in-healthy-volunteers/
-
October 1, 2012 at 6:30 PM eastern, Dr. Amir Hamrahian will answer our questions about Cushing's, pituitary or adrenal issues and Korlym (mifepristone) in BlogTalkRadio at http://www.blogtalkr...s-our-questions You may listen live at the link above. The episode will be added to the Cushing's Help podcast after the show is over. Listen to the podcasts by searching for Cushings in the iTunes podcast area or click here: http://itunes.apple....ats/id350591438 Dr. Hamrahian has had patients on Korlym for about 4 years. Please submit your questions below or email them to CushingsHelp@gmail.com before Sunday, September 30. From Dr. Hamrahian's bio at http://my.clevelandc...x?doctorid=3676 Amir Hamrahian, M.D. (216) 444-6568 http://my.clevelandc...5&DoctorID=3676 Appointed: 2000 Request an Appointment Research & Publications † ( † Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.) Biographical Sketch Amir H. Hamrahian, MD, is a Staff member in the Department of Endocrinology, Diabetes and Metabolism at Cleveland Clinic's main campus, having accepted that appointment in 2005. Prior to that appointment, he was also a clinical associate there for nearly five years. His clinical interests include pituitary and adrenal disorders. Dr. Hamrahian received his medical degree from Hacettepe University in Ankara, Turkey, and upon graduation was a general practitioner in the provinces of Hamadan and Tehran, Iran. He completed an internal medicine residency at the University of North Dakota, Fargo, and an endocrinology fellowship at Case Western Reserve University and University Hospitals, Cleveland. In 2003, he received the Teacher of the Year award from Cleveland Clinic's Department of Endocrinology, Diabetes and Metabolism. Dr. Hamrahian speaks three languages -- English, Turkish and Farsi -- and is board-certified in internal medicine as well as endocrinology, diabetes and metabolism. He is a member of the Endocrine Society, Pituitary Society and the American Association of Clinical Endocrinologists. Education & Fellowships Fellowship - University Hospitals of Cleveland Endocrinology Cleveland, OH USA 2000 Residency - University of North Dakota Hospital Internal Medicine Fargo, ND USA 1997 Medical School - Hacettepe University School of Medicine Ankara Turkey 1991 Certifications Internal Medicine Internal Medicine- Endocrinology, Diabetes & Metabolism Specialty Interests Cushing syndrome, acromegaly, pheochromocytoma, prolactinoma, primary aldosteronism, pituitary disorders, adrenal tumor, adrenocortical carcinoma, MEN syndromes, adrenal disorders Awards & Honors Best Doctors in America, 2007-2008 Memberships Pituitary Society Endocrine Society American Association of Clinical Endocrinologists American Medical Association Treatment & Services Radioactive Iodine Treatment Thyroid Aspiration Thyroid Ultrasound Specialty in Diseases and Conditions Acromegaly Addison’s Disease Adrenal disorders Adrenal insufficiency Adrenal Insufficiency and Addison’s Disease Adrenal Tumors Adrenocortical Carcinoma Adrenoleukodystrophy (ALD) Amenorrhea Androgen Deficiency (Low Testosterone) Androgen Excess Calcium Disorders Carcinoid Syndrome Conn's Syndrome Cushing's Syndrome Empty sella Erectile Dysfunction Familial Multiple Endocrine Neoplasia Fasting hypoglycemia Flushing Syndromes Galactorrhea Goiter Growth hormone deficiency Growth hormone excess Gynecomastia Hirsutism Hyperaldosteronism Hyperandrogenism Hyperprolactinemia Hypertension - High Blood Pressure Hyperthyroidism Hypocalcemia Hypoglycemia Hypogonadism Hypoparathyroidism Hypophysitis Hypopituitarism Hypothyroidism Mastocytosis Menopause, Male Menstrual Disorders Paget's Disease Panhypopituitarism Parathyroid Cancer Parathyroid Disease and Calcium Disorders Pheochromocytoma Pituitary Cysts Pituitary Disorders Pituitary stalk lesions Pituitary Tumors Premenstrual Syndrome (PMS) Primary Hyperaldosteronism Primary Hyperparathyroidism Prolactin Excess States Prolactinoma Thyroid and pregnancy Thyroid Cancer Thyroid Disease Thyroid Nodule
- 11 replies
-
- 1
-
-
- mifepristone
- Dr. Amir Hamrahian
- (and 7 more)
-
This BlogTalkRadio episode will be with a patient who has been on Korlym and an experienced physician to better share his views and expertise with patients. The doctor will most likely be Dr. Richard A. from the University of Michigan. Stay tuned!
-
Corcept Therapeutics (NASDAQ:CORT) announced that it would be ready to ship Korlym to patients by April 11th, three weeks ahead of the company’s previously announced launch date. “Cushing’s syndrome is a life altering and life threatening disease,” said Joseph K. Belanoff, M.D., the company’s Chief Executive Officer. “We have worked hard to bring this first-in-class treatment to patients as quickly as possible.” On February 17, 2012, the U.S. Food and Drug Administration (FDA) approved KorlymTM (mifepristone) 300 mg Tablets as a once-daily oral medicine 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. Physicians and patients seeking more information can visit http://www.korlym.com. Korlym is distributed in 300 milligram tablets to be taken once each day. The wholesale acquisition price of Korlym is $0.62 per milligram. The FDA-approved labeling instructs physicians to titrate each patient’s Korlym dose to clinical efficacy by assessing tolerability and degree of improvement in Cushing’s syndrome manifestations. In the first six weeks, these manifestations may include changes in glucose control, anti-diabetic medication requirements, insulin levels and psychiatric symptoms. After two months, assessment may also be based on improvements in cushingoid appearance, acne, hirsutism, striae or decreased body weight, along with further changes in glucose control. Patient Assistance Programs “Our highest priority is that every patient who is prescribed Korlym will receive it,” said Dr. Belanoff. To that end, the company has launched a comprehensive financial assistance and patient support program. A dedicated team of Corcept case managers will help patients understand their insurance benefits and the financial and medical support programs available to them. “Patients face tremendous challenges managing their illness – from finding physicians familiar with the disease to navigating the complexities of insurance reimbursement to paying for the cost of care,” said Dr. Belanoff. “We are determined that none of these barriers will keep patients from receiving the benefits of Korlym.” About Cushing’s Syndrome Endogenous Cushing’s syndrome is a rare and life-threatening endocrine disorder that results from long-term exposure to excess levels of the hormone cortisol. This excess is caused by tumors that usually occur in the pituitary or adrenal glands that over-produce, or prompt the over-production of, cortisol. Although cortisol at normal levels is essential to health, in excess it causes a variety of problems, including hyperglycemia, upper body obesity, a rounded face, stretch marks on the skin, an accumulation of fat on the back, thin and easily bruised skin, muscle weakness, bone weakness, persistent infections, high blood pressure, fatigue, irritability, anxiety, psychosis and depression. Women may have menstrual irregularities and facial hair growth, while men may have decreased fertility or erectile dysfunction. More than 70 percent of Cushing’s syndrome patients suffer from glucose intolerance or diabetes. The treatment of an endogenous Cushing’s syndrome patient depends on the cause. The first-line approach is surgery to remove the tumor. If surgery is not successful or is not an option, radiation may be used, but that therapy can take up to ten years to achieve full effect. Surgery and radiation are successful in only approximately one-half of all cases. If left untreated, Cushing’s syndrome has a five-year mortality rate of 50 percent. An orphan disease, Cushing’s syndrome occurs in about 20,000 people in the United States, mostly women between the ages of 20 and 50. About Korlym™ (mifepristone) 300 mg Tablets Korlym is a once-daily oral medication that blocks the glucocorticoid receptor type II (GR-II) to which cortisol normally binds. By blocking this receptor, Korlym inhibits the effects of excess cortisol in Cushing’s syndrome patients. The FDA has designated Korlym as an Orphan Drug, a special status designed to encourage the development of medicines for rare diseases and conditions. Because Korlym is an Orphan Drug, Corcept will have marketing exclusivity for the FDA-approved indication until February 2019. IMPORTANT SAFETY INFORMATION WARNING: TERMINATION OF PREGNANCY See full prescribing information for complete boxed warning. Mifepristone has potent antiprogestational effects and will result in the termination of pregnancy. Pregnancy must therefore be excluded before the initiation of treatment with Korlym, or if treatment is interrupted for more than 14 days in females of reproductive potential. Contraindications Pregnancy Use of simvastatin or lovastatin and CYP 3A substrates with narrow therapeutic range Concurrent long-term corticosteroid use Women with history of unexplained vaginal bleeding Women with endometrial hyperplasia with atypia or endometrial carcinoma 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 patient also has a hemorrhagic disorder or is on anti-coagulant 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 can increase plasma levels significantly. Use only when necessary and limit dose to 300 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. To report suspected adverse reactions, contact Corcept Therapeutics at 1-855-844-3270 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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. Limit mifepristone dose to 300 mg per day when used with strong CYP3A inhibitors. 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 Nursing mothers: Discontinue drug or discontinue nursing. Please see the accompanying full Prescribing Information including boxed warning atwww.corcept.com/prescribinginfo.pdf Please see the accompanying Medication Guide at www.corcept.com/medicationguide.pdf About Corcept Therapeutics Incorporated Corcept is a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic and psychiatric disorders. Korlym, a first generation GR-II antagonist, is the company’s first FDA-approved medication. The company has a portfolio of new selective GR-II antagonists that block the effects of cortisol but not progesterone. Corcept also owns an extensive intellectual property portfolio covering the use of GR-II antagonists, including mifepristone, in the treatment of a wide variety of psychiatric and metabolic disorders. The company also holds composition of matter patents for its selective GR-II antagonists. Statements made in this news release, other than statements of historical fact, are forward-looking statements. Forward-looking statements are subject to a number of known and unknown risks and uncertainties that might cause actual results to differ materially from those expressed or implied by such statements. For example, there can be no assurances that clinical results will be predictive of real-world use, or regarding the pace of Korlym’s acceptance by physicians and patients, the reimbursement decisions of government or private insurance payers, the effects of rapid technological change and competition, the protections afforded by Korlym’s Orphan Drug Designation or by Corcept’s other intellectual property rights, and the cost, pace and success of Corcept’s other product development efforts. These and other risks are set forth in the Company's SEC filings, all of which are available from our website (www.corcept.com) or from the SEC's website (www.sec.gov). We disclaim any intention or duty to update any forward-looking statement made in this news release. CONTACT: Investor Contact Charles Robb Chief Financial Officer Corcept Therapeutics 650-688-8783
-
Have questions about the new Korlym? How about Korlym vs ketoconazole? About medical vs surgical treatment for Cushing's. Ask Dr. Theodore F.. Theodore C. F., M.D., Ph.D. has opened a private practice, specializing in treating patients with adrenal, pituitary, thyroid and fatigue disorders. Dr. F. has privileges at Cedars-Sinai Medical Center and Martin Luther King Medical Center. His practice includes detecting and treating hormone imbalances, including hormone replacement therapy. Dr. F. is also an expert in diagnosing and treating pituitary disorders, including Cushings disease and syndrome. Dr. F.'s career reflects his ongoing quest to better understand and treat endocrine problems. With both medical and research doctoral degrees, he has conducted studies and cared for patients at some of the country's most prestigious institutions, including the University of Michigan, the National Institutes of Health, Cedars-Sinai Medical Center, and UCLA's Charles Drew University of Medicine and Science. Read Dr. F.'s First Guest Chat, November 11, 2003. Read Dr. F.'s Second Guest Chat, March 2, 2004. Listen to Dr. F. First Live Voice Interview, January 29, 2009. Listen to Dr. F. Second Live Voice Interview, March 12, 2009. Listen to Dr. F. Third Live Voice Interview, February 13, 2011. Listen live at http://www.blogtalkradio.com/cushingshelp/2012/03/13/questions-about-medical-therapies-for-cushings Call in to ask your question at (646) 200-0162 This interview will be archived afterwards at the same link and on iTunes Cushie Podcasts This post has been promoted to an article
-
FDA NEWS RELEASE For Immediate Release: Feb. 17, 2012 Media Inquiries: Morgan Liscinsky, 301-796-0397; morgan.liscinsky@fda.hhs.gov Consumer Inquiries: 888-INFO-FDA FDA approves Korlym for patients with endogenous Cushing’s syndrome Today, Korlym (mifepristone) was approved by the U.S. Food and Drug Administration to control high blood sugar levels (hyperglycemia) in adults with endogenous Cushing’s syndrome. This drug was approved for use in patients with endogenous Cushing’s syndrome who have type 2 diabetes or glucose intolerance and are not candidates for surgery or who have not responded to prior surgery. Korlym should never be used (contraindicated) by pregnant women. Prior to FDA’s approval of Korlym, there were no approved medical therapies for the treatment of endogenous Cushing’s syndrome. Endogenous Cushing’s syndrome is a serious, debilitating and rare multisystem disorder. It is caused by the overproduction of cortisol (a steroid hormone that increases blood sugar levels) by the adrenal glands. This syndrome most commonly affects adults between the ages of 25 and 40. About 5,000 patients will be eligible for Korlym treatment, which received an orphan drug designation by the FDA in 2007. Korlym blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels. The safety and efficacy of Korlym in patients with endogenous Cushing’s syndrome was evaluated in a clinical trial with 50 patients. A separate open-label extension of this trial is ongoing. Additional evidence supporting the agency’s approval included several safety pharmacology studies, drug-drug interaction studies and published scientific literature. Patients experienced significant improvement in blood sugar control during Korlym treatment, including some patients who had marked reductions in their insulin requirements. Improvements in clinical signs and symptoms were reported by some patients. The most common side effects experienced by endogenous Cushing’s syndrome patients treated with Korlym in clinical trials were nausea, fatigue, headache, arthralgia, vomiting, swelling of the extremities, dizziness and decreased appetite. Other side effects of Korlym include adrenal insufficiency, low potassium levels, vaginal bleeding and a potential for heart conduction abnormalities. Certain drugs used in combination with Korlym may increase its drug level. Health care professionals must be aware of the potential for drug-drug interactions and adjust dosing or avoid using certain drugs with Korlym. Korlym should never be used by pregnant women. Although pregnancy is an extremely rare occurrence in Cushing’s syndrome patients because of the suppressive effect of excess cortisol on female reproductive function, Korlym will carry a Boxed Warning advising health care professionals and patients that the therapy will terminate a pregnancy. The FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) is not necessary for Korlym to ensure that the benefits outweigh the risks for patients with endogenous Cushing’s syndrome. Several factors were considered in this determination including the following: There are no other approved medical therapies for this debilitating form of Cushing’s syndrome and very sick patients would suffer if impediments to access were imposed. The number of Cushing’s syndrome patients who will require treatment with Korlym is small, with an estimated 5,000 patients being eligible for treatment. The number of health care professionals in the United States who would potentially prescribe Korlym is very small and highly specialized. They are familiar with the risks of Korlym treatment in the endogenous Cushing’s syndrome population and frequently monitor patient status. The risks of Korlym treatment in the intended population can be managed through physician and patient labeling. The risks associated with Korlym will be outlined in a medication guide for patients. The company has voluntarily proposed distributing Korlym through a central pharmacy to ensure the timely, convenient and appropriate delivery of the drug to Cushing’s patients or to the health care institutions where this therapy may be initiated. Most retail pharmacies are unlikely to keep adequate supplies of the drug for this rare condition and central distribution will give patients with Cushing’s syndrome better access to Korlym. Korlym is manufactured by Corcept Therapeutics of Menlo Park, Calif. For more information: Approved Drugs: Questions and Answers The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products. # Visit the FDA on Facebook RSS Feed for FDA News Releases [what is RSS?] Page Last Updated: 02/17/2012 From http://www.fda.gov/N...s/ucm292462.htm This post has been promoted to an article
