BBC News says we are a step closer to microchips that can be “implanted under a patient’s skin to control the release of drugs”.
The news was based on a study that tested the use of advanced microchips containing tiny drug reservoirs that can be remotely triggered to release medication into the body. Creating workable drug-release chips has long been a goal of researchers, as it could help people take the correct dose of vital medicines such as insulin.
In this particular trial, reported to be the first of its kind, eight women were given the chips filled with a drug to combat osteoporosis. The drug, teriparatide, is normally delivered by daily injection, but researchers found that using the chips produced similar physical results to injections. Also, there were no toxic or adverse events, due to either the microchip or the drug, and all the patients reported that it did not impact on their quality of life.
This study throws up a range of possible uses for microchip-based drug delivery, which could one day be used for the treatment of wider conditions that require frequent, scheduled dosing, particularly where standard treatment is through injection.
However, much more testing of the technology will be needed to firmly establish its safety, and to see whether there could be wider applications. One key consideration though, would be whether the use of this advanced technology can actually prove better or cheaper than the use of injections.
Where did the story come from?
The study was carried out by researchers from MicroCHIPS, Inc, (a private company producing medical microchips ; the Harvard Medical School; Case Western Reserve University; On Demand Therapeutics, Inc, and the Massachusetts Institute of Technology. It was funded by MicroCHIPs, Inc.
The study was published in the peer-reviewed scientific journal Science Translational Medicine.
The results of this study have also been presented at the annual meeting of the American Association for the Advancement of Science (AAAS .
The story appeared on the BBC and a number of newspapers, including the Daily Mail, the Daily Mirror and The Independent.
Most of the coverage of the story was good. However, alongside The Independent’s main article the newspaper featured an opinion-based section discussing potential uses of the device, including allowing psychiatrists to trigger doses in schizophrenic patients when they resist injections of medication. There is a distinct difference between using medical devices to structure the delivery of medication and using them to force people to take medication against their will.
It seems unlikely that medical groups would find this theoretical use to be ethically acceptable, and it should be noted that the treatment of mental health problems was not assessed in the study or in other coverage.
The Independent also used a photograph of a distressed man huddled on the floor wearing no shoes, intended to illustrate schizophrenia. While the condition can certainly involve periods of acute problems and distress, it seems to a rather extreme and particularly negative depiction of someone with schizophrenia.
What kind of research was this?
This was a small cohort study of a drug delivery microchip, implanted under the skin. The microchip contains tiny drug reservoirs and can be programmed to wirelessly release discrete doses of a medication.
This particular study used the drug teriparatide, prescribed by specialists only for the treatment of severe osteoporosis (bone weakening . It is normally delivered by daily injection and given for a maximum treatment period of two years only.
The researchers aimed to see whether the drug released from the device had similar ‘pharmacokinetics’ (adsorption, distribution, metabolism and excretion and biological effect to the drug administered by standard injection. They also monitored how reliable and reproducible drug release from the microchip was, and if there were any side effects of the implant.
This was the first clinical trial of this microchip. As the researchers state, further development is required to ensure proper operation of implanted devices, and devices containing more reservoirs will be needed if the device were to provide regular doses over one or more years. In addition, before this technology becomes available, it will have to be tested in larger, controlled trials.
What did the research involve?
Eight women with osteoporosis, aged between 65 and 70, were recruited for the study. The drug delivery microchip was implanted under the skin, just under the waistline. The devices were implanted for four months. Eight weeks after implantation, the microchip started releasing daily doses of teriparatide for a period of 20 days. Blood samples were drawn regularly to monitor the pharmacokinetics and to determine levels of bone markers. A safety assessment was also performed.
After the 20 days of drug release from the device, the researchers administered the osteoporosis drug by injection, and again took blood samples, so that release from the microchip and from the injection could be compared.
What were the basic results?
In one patient, feedback from chip indicated that the drug was not being released. The results from this patient were excluded.
Drug released from the microchip in the seven other patients had similar pharmacokinetics to drug administered by injection, and bone markers indicated that drug released from the microchip increased bone formation as expected. However, the effectiveness of medication released from the microchip was not compared to the effectiveness when given by injection.
There were no toxic or adverse events due to the device or drug. Patient response to the implant was also favourable, stating that it did not impact upon their quality of life.
How did the researchers interpret the results?
The researchers concluded that the programmable implant was able to deliver teriparatide at scheduled intervals, with pharmacokinetics similar to injections ‘without the pain and burden of daily injections’.
Conclusion
This study was a small clinical trial, performed in eight women, of an implantable microchip-based drug delivery device. It found that the microchip could deliver the osteoporosis drug teriparatide with similar pharmaceutical properties to injections, including adsorption, distribution, excretion and metabolism by the body. There were no toxic or adverse events due to either the microchip or the drug, and the patients all responded favourably to the implant, stating it did not affect quality of life.
Larger controlled trials comparing this device with conventional injected teriparatide would be needed to confirm the safety and efficacy findings. Furthermore, trials may need to assess use of the chip over a longer period - on prescription, teriparatide may be administered by daily injection for up to two years.
The findings also suggest that this microchip-based drug delivery device may have the potential to be used for the treatment of wider conditions that require frequent, scheduled dosing, particularly where standard treatment is through injection. However, much more testing of the technology will be needed to see whether there could be wider applications.
Analysis by Bazian
Links To The Headlines
Dawn of the age of wireless medicine. The Independent, February 17 2012
'Wireless medicine' helps solve one of doctors' biggest problems - getting patients to take drugs. The Independent, February 17 2012
New microchip will let doctor administer drugs into your body over the phone. Daily Mirror, February 17 2012
'Pharmacy on a chip' gets closer. BBC News, February 17 2012
Links To Science
Farra R, Sheppard NF, McCabe L, et al. First-in-Human Testing of a Wirelessly Controlled Drug Delivery Microchip. Science Translational Medicine. Published online February 16 2012
sincerely
clueless:
President Obama, you may remember, tried to pass cap-and-trade and tried to get control not only of the health care system but of the energy industry, the manufacturing industry, another two big sectors of this economy, and using this facade of man-made global warming. I stood up and fought against those things. Why? because they will destroy the very foundation of prosperity in our country.These liberal NASA scentists managed to infiltrate right-wing think-tanks, covertly develop the Cap-n-Trade concept, and persuade Republicans to embrace it! Until Obama warmed to it, at which point it suddenly became an attack on the very foundation of prosperity in our country.
- Space is
beautiful and violent! But the proposed cuts in planetary science announced by the White House this week may end up postponing answers to the most
important questions in science by years or decades.
Researchers using embryonic stem cells report they successfully treated blindness in two patients. Regardless if that study holds up, regerenative medicine is coming. I would not want to be on the conservative side waving around a personhood amendment and cheering on bills allowing employers to with hold treatment based on cultish whims, when the first paralyzed kid gets up out of their wheelchair and walks.
- On a lighter, geeky note, this
new mount is so cool! I don't want to chase the dragon, I just want to virtually ride it. Gimme Gimme Gimme!
- Let us now to turn to the science and politics of women's health, where the GOP is busy self immolating, and add a little
gasoline:
The same people pushing for these mandatory sonogram bills have also been pushing for years for “conscience clauses” ...like allowing pharmacists to refuse to fill prescriptions for birth control. So what do you suppose they would say if a doctor refused to perform this government-mandated invasive sonogram as a matter of conscience?
Whistleblower made complaint to IRS over climate science attack machine's tax-exempt status, Guardian learns
The Heartland Institute, the libertarian thinktank whose project to undermine science lessons for schoolchildren was exposed this week, faces new scrutiny of its finances – including its donors and tax status.
The Guardian has learned of a whistleblower complaint to the Internal Revenue Service about Heartland's 501(c (3 tax-exempt status.
There was also a call from a group of climate scientists who have personally been on the receiving end of attacks from Heartland and bloggers funded by the thinktank, and whose email was posted online after a notorious 2009 hack, for Heartland to "recognise how its attacks on science and scientists have poisoned the debate about climate change policy,"
in a letter made available exclusively to the Guardian.
The unauthorised release of internal documents indicated Heartland had received $14m over several years from a single anonymous donor as well as tobacco and liquor companies and corporations pledged to social responsibility, including the General Motors Foundation.
The release of the donors' list led a number of environmental organisations to demand GM, which gave $30,000, and Microsoft, which gave $59,908 in free software, to sever their ties with a thinktank that has a core mission of discrediting climate science.
An online petition on Friday criticised GM for taking the auto industry bailout and using taxpayer funds to a thinktank spreading what they say is climate misinformation. GM has admitted funding Heartland, pointing out that the money was for its work on health issues, not climate change.
"While General Motors has a mixed record on global warming, lately they've been doing all the right things, like investing heavily in the electric Chevy Volt. At the same time, they've been kept afloat by American taxpayers through a massive bailout. That means our tax dollars are ending up in the hands of the Heartland Institute," the petition said.
Others are focusing on Heartland's support from the tobacco industry as well as major health and pharmaceutical companies for a thinktank which has opposed smoking bans and healthcare reform.
John Mashey, a retired computer scientist and Silicon Valley executive, said he filed a complaint to the IRS this week that said Heartland's public relations and lobbying efforts violated its non-profit status.
Mashey said he sent off his audit, the product of three months' research, just a few hours before the unauthorised release of the Heartland documents.
Mashey said in a telephone interview that the complaint looked at the activities of Heartland and t
wo other organisations that have been prominent in misinforming the public about climate change, the Science and Environmental Policy Project, run by Fred Singer, and the Centre for the Study of Carbon Dioxide and Global Change, run by Craig Idso. Both men were funded by Heartland, with Idso receiving $11,600 per month and Singer $5,500 a month, according to the 2012 budget.
Heartland is also funding contrarians in Canada and other countries, the documents show.
"I believe there was a massive abuse of 501c(3 ," Mashey said. "My extensive study of these think anks showed numerous specific actions that violated the rules – such as that their work is supposed to be factually based. Such as there was a whole lot of behaviour that sure looked like lobbying and sending money to foreign organisations that are not charities."
Mashey later published his audit of Heartland finances in Desmogblog, which was the first outlet to run the trove of Heartland documents.
Others were demanding more disclosure from Heartland about its donors and its activities.
In a letter that was published on Friday and then subsequently removed, more than 30 leading health professionals and scientists from the US, Britain, Australia and New Zealand called on Heartland to come clean. "What motivates the Heartland Institute? As climate scientists and health professionals, we view the systematic manipulation and suppression of climate science for private benefit as confusing at best, and inhumane at worst," the letter said.
"It is in the public, national, and global interest for all funding behind their activities to be revealed. This allows people to make up their own minds about the truth of the climate change threat, so that action can be planned in the light of reality rather than the murky shadows of secretly funded disinformation."
In a separate initiative, seven climate scientists wrote an open letter calling on Heartland to see the moment of exposure as an opportunity to change tack.
The scientists, who included Kevin Trenbeth at the National Centre for Atmospheric Research and Ben Santer at the Lawrence Livermore National Labs, also took Heartland to task for its response to the 2009 and 2011 hacks of climate scientists' emails. "The Heartland Institute has had no qualms about utilising and distorting emails stolen from scientists," the letter said.
"The Heartland Institute has chosen to undermine public understanding of basic scientific facts and personally attack climate researchers rather than engage in a civil debate about climate change policy options," the letter said.
"We hope the Heartland Institute will begin to play a more constructive role in the policy debate. Refraining from misleading attacks on climate science and climate researchers would be a welcome first step toward."
Terms & Conditions |
More Feeds
US-based scientists have been trialling a remote-controlled drug delivery device with exciting results.
The implanted chip was given to female osteoporosis patients and its contents supplied in controlled doses from the outside. Those involved have said the doses given were correct and no side effects were reported.
Therefore, the world's moved one step closer to operational drug-streaming microchips and details of the team's work were unveiled at the AAAS (American Association for the Advancement of Science organisation's AGM, which began on 16 February and concludes on 20 February.
Microchip Drug Delivery
They also made it into the current edition of the Science Translational Medicine publication and come 15 years after the ‘telemedicine' concept was dreamed up by two MIT professors. They've since launched a corporate MIT spin-off - MicroCHIPS Inc - to develop the microchip drug delivery idea.
"You could literally have a pharmacy on a chip", MicroCHIPs' Professor Robert Langer was quoted as having said in an MIT press release. He added: "You can do remote control delivery, you can do pulsatile drug delivery and you can deliver multiple drugs."
The telemedicine drug trial involved seven test subjects - all women, all aged between 65 and 70 and all suffering from osteoporosis. At the start of 2011, the chips were implanted, under anaesthetised surgical conditions and they remained in the women until May.
Into each of these chips were loaded 20 teriparatide doses stored in separate chambers. These were sealed by titanium and platinum layers and, when an electrical current was applied, these layers broke up, allowing the drug to break free. Not only can these chips be told, in real time, when to discharge the drugs inside them, but they can also be programmed ahead of time, so they release the drugs to a precise and planned schedule.
Remote-Controlled Drug Delivery
At present, the operational range of the remote-controlled drug delivery set-up is just a few inches, but the development team expect to be able to achieve a greater distance in due course.
"The whole device is approximately 3cm by 5cm and 1cm thick", MicroCHIPS Inc's chief operating officer, Professor Robert Farra, commented. He continued: "Like other medical implants, it's made out of biocompatible materials. It has a housing with the electronics on the inside, together with the microchips that contain the discrete doses of the hormone.
"Patients with chronic diseases, regular pain-management needs or other conditions that require frequent or daily injections could benefit from this technology."
Photo: M. Scott Brauer - Courtesy MIT
Source: MicroChips
Coming soon, whether we like it or not! The
Financial Times reports:
A wirelessly controlled implant, which delivers precise drug doses into the patient’s body, has had a successful first clinical trial, bringing the possibility of the “pharmacy on a chip” that could transform drug delivery closer.
Researchers used the microchip device to give seven women with osteoporosis daily doses of a bone-strengthening hormone that was normally injected. The results were announced at the start of the American Association for the Advancement of Science annual meeting on Thursday.
The device could transform drug delivery and help usher in a new era of telemedicine – delivering healthcare over a distance – said Robert Langer, a professor at the Massachusetts Institute of Technology where the project started 15 years ago.
“You could literally have a pharmacy on a chip,” he said. “You can do remote control delivery, you can do pulsatile drug delivery, and you can…
http://www.jstage.jst.go.jp/article/jphs/advpub/0/1202100661/_pdf (excerpts follow
J Pharmacol Sci. 2012 Feb 14,
Takai S,
Jin D,
Miyazaki M, Dept of Pharmacology, Osaka Medical College, Japan
A mast cell-produced enzyme, chymase, generates angiotensin II and also converts precursors of TGF-? and MMP-9 to their active forms. Chymase also strongly promotes accumulation of inflammatory cells. These multiple functions of chymase may play an important role in the development and promotion of various diseases. In fact, chymase inhibitors have been shown to prevent nonalcoholic steatohepatitis, intestinal inflammation, and adhesion formation after surgery and cardiovascular and renal damage.
Thus, chymase inhibitors may be useful for preventing damage to various organs via multiple mechanisms without lowering blood pressure.
HAIR HELPERS
Mason Pearson filling up a bit too quickly? You're not alone. "I used to treat about three patients a month for hair loss, and now it's roughly three per day," says NYC-based dermatologist
Macrene Alexiades-Armenakas, MD, who attributes the "astounding increase" of hair loss to stress-induced testosterone production, which causes hair follicles to slow down.
RELATED ON ELLE:
The Best Haircut For Your Face Shape
Double Up: To jump-start growth, Alexiades often suggests combining her "mainstay" treatment, Rogaine (minoxidil , with a topical prescription of testosterone-regulating spironolactone (like many prescription therapies, the combo is not for women trying to get pregnant, or who are pregnant or nursing . Miami- and New York–based dermatologist Fredric Brandt, MD, sends patients home with biotin supplements (which help the body metabolize amino acids and protein, the basic building blocks of hair , plus a prescription for a pharmacist-blended compound of eyelash-boosting Latisse (which many derms have found also stimulates hair growth on the scalp and liquid Retin-A.
"The retinoid opens up the follicles and increases the penetration of Latisse," Brandt says. "It makes a huge difference in speeding up results." With a three-milliliter bottle of Latisse costing roughly $150 (Dom Perignon suddenly seems like a steal , risk-takers are ordering generic forms of key ingredient bimatoprost from Canada. But Brandt cautions against the money-saving strategy: "Unless it comes from a trusted pharmacy, it may be counterfeit." Initial FDA trials for an allover scalp formulation of Latisse are in the works.
Fast Fixes: To camouflage a wide part (one of the signs of thinning hair , New York colorist Marie Robinson gives clients a base color that's a similar shade to their scalp (making the part less noticeable . Next, Robinson weaves in highlights, which roughen up hair's cuticles, creating fullness and visual depth so that strands appear thicker.
FACE TIME
With new injectables making their way into derm offices, treating the face is becoming a highly bespoke science. "People have different lines and muscle functions," NYC-based dermatologist Francesca Fusco, MD, says. "Having new options gives me a more individualized approach to each patient."
RELATED ON ELLE:
Celebrity Skin Secrets
Filler Frontier: Popular in Europe, Belotero (a
hyaluronic acid filler awaiting FDA approval will soon find its niche among injectables in the U.S. Thanks to its texture, it's an ace at treating shallow nasal labial folds and undereye bags. "Fillers can cast blue discoloration under the skin if injected too close to the skin's surface," Brandt says, describing what is known as the Tyndall effect (aptly named after the nineteenth-century physicist who discovered why the sky is blue . Because Belotero's consistency is thinner than that of other fillers, "it will be a good option for the most superficial injections," Brandt says.
RELATED ON ELLE:
New Treatments for Thinner Thighs
Freeze Frame: The FDA recently approved Xeomin, a third type of botulinum toxin, for treating frown lines. "Xeomin is just pure botulinum toxin," Fusco says. "No additives means less chance of antibodies being formed. If someone develops a strong antibody response, the injection may not work."
Whiteout: A recent study presented at the World Congress of Dermatology suggests a new use for hardworking eyelash serum Latisse: treating vitiligo (patches of depigmented skin and
UV-induced white sunspots (which are harder to banish than brown spots . "The main ingredient, bimatoprost, causes cells to produce more melanin," Fusco says, which explains why eyelids may darken when treating lashes with the serum. Initial study results were promising: The 10 trial participants saw 100 percent repigmentation on the treated facial areas.
Visit
ELLE.COM to continue reading and check out the
Forever 21 "Tool Kit"
MENLO PARK, Calif. - February 17, 2012
Corcept Therapeutics (NASDAQ:CORT announced today that the U.S. Food and Drug Administration (FDA has approved Korlym™ (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 diabetes mellitus type 2 or glucose intolerance and have failed surgery or are not candidates for surgery.
"We appreciate the FDA's diligent attention to our NDA and its grant of approval on the PDUFA date," said Joseph K. Belanoff, M.D., the company's Chief Executive Officer. "We plan to make Korlym available to patients by May 1 through a distribution system designed to support both patients and prescribers."
Corcept will be the sole marketer of Korlym. "A relatively small number of endocrinologists regularly treat patients with Cushing's syndrome," added Dr. Belanoff. "These doctors can be reached without a large sales and marketing infrastructure." The company has begun hiring Medical Science Liaisons to inform practitioners about the drug, which will be dispensed by the leading specialty pharmacy company CuraScript SP, a subsidiary of Express Scripts.
"Korlym is a significant advance in the treatment of patients suffering from the debilitating symptoms of Cushing's syndrome," said Robert L. Roe, M.D., Corcept's President. "For the first time, these patients have access to an approved therapy when surgery has failed or is not an option."
Korlym clinical trial investigator Amir Hamrahian, M.D., Department of Endocrinology, Diabetes and Metabolism at the Cleveland Clinic said, "There are not many effective treatment options for patients with Cushing's syndrome. Although surgery is standard first line treatment for the disease, it is not always successful and not all patients are candidates. As part of the clinical trial, I have used Korlym successfully and my patients continue to do well on the medicine. I'm excited to be able to continue using Korlym in these patients and others who need it. This medicine's approval gives me a much needed tool to better treat patients."
Dr. Hamrahian's comments were seconded by Maureen V., a patient in Corcept's Phase 3 clinical trial: "I had pituitary surgery to treat my Cushing's syndrome. Unfortunately, my surgery wasn't successful. I was lucky to get into the study and get Korlym treatment. I have been taking the medicine successfully for over a year, and I am extremely happy that it was approved by the FDA. Now I know I'll be able to keep taking it. It has made a big difference in my life."
Clinical Trial Results Supporting FDA Approval
The clinical data supporting the FDA approval of Korlym resulted from an uncontrolled, open-label, multi-center, 24-week phase III study of 50 patients who had endogenous Cushing's syndrome and were either not eligible for or had relapsed from surgery and were either glucose intolerant (29 patients or had hypertension (21 patients . Within the glucose intolerant group, 60 percent of patients had a greater than 25 percent reduction from baseline in the area under the curve in the oral glucose tolerance test. In this group, mean hemoglobin A1C (HbA1C was reduced from 7.4 percent to 6.3 percent. All 14 patients with above-normal HbA1C levels at baseline experienced reductions. Eight of these 14 normalized their HbA1C. Antidiabetic medications were reduced in seven of the 15 patients with diabetes mellitus type 2 and remained constant in the others.
Patients who responded to therapy were allowed enrollment in an extension trial. Eighty-eight percent of the patients who completed the trial chose to do so.
A peer-reviewed analysis of the study results will soon be published in a leading journal.
Patients in the study started Korlym treatment on a dose of 300 mg administered once daily. Their dose was then titrated to maximum clinical effect. As indicated in the medicine's label, physicians prescribing Korlym may determine the appropriate dose for each patient 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, decreased body weight, along with further changes in glucose control.
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 for treatment of the clinical manifestations of endogenous Cushing's syndrome. Orphan Drug designation is 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 consistent with the FDA's designation until February 2019.
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.
Conference Call Information
Corcept will hold a conference call on Tuesday, February 21, 2012 at 9:00 a.m. Eastern Time (6:00 a.m. Pacific Time to discuss this announcement. To participate in the live call please dial 1-800-264-7882 from the United States or +1-847-413-3708 internationally. The pass code is 31838602. Please dial in approximately 10 minutes before the start of the call.
A replay of the conference call will be available through March 6, 2012 at 1-888-843-7419 from the United States and +1-630-652-3042 internationally. The pass code is 31838602.
IMPORTANT SAFETY INFORMATION
See full prescribing information for complete boxed warning.
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 at
www.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.
CONTACTS:
Charles Robb
Chief Financial Officer
Corcept Therapeutics
650-688-8783
Media Contact
Alissa Maupin
Communications Strategies, Inc.
973-635-6669
Leerink Swann's Global Healthcare Conference 2012 featured two presentations and several more private discussions featuring Center for Drug Evaluation and Research ("CDER" Director Janet Woodcock, M.D., as well as her colleagues, Steven Kozlowski, M.D., CDER's Director of Office of Biotechnology Products, and Keith Own Webber, Ph.D., CDER's Deputy Director, Office of Pharmaceutical Science, Acting Director, Office of Generic Drugs. The trio presented a discussion "Biosimilars Take the Stage" followed by Woodcock's Keynote Address on "New Trends in Drug Regulation and Innovation", and several smaller question-and-answer-format meetings regarding these topics and more. This is part one of a two-part series and concerns the biosimilars presentations. Part two will be posted on Tuesday.
Leerink's biosimilars session was moderated by Joshua Schimmer, M.D. and Jason Gerberg, J.D./M.B.A. with co-moderators Seamus Fernandez and Joseph Schwartz. Kozlowski provided some preliminary remarks followed by a question-and-answer format by the moderators. Kozlowski explained that the purpose of FDA's first set of biosimilars guidances, which we initially reported on
here, was to set the scientific framework for approaching biosimilar product development and provide some interpretations of the new statutory terminology. Kozlowski explained that FDA decided to take a "totality of the evidence" and "stepwise approach", where the structural similarity of the biosimilar, as demonstrated by the sponsor, drives the development of the clinical program to support approval.
Woodock added that FDA has had a challenge to retrain their reviewers to think of biosimilar review as an "inverted pyramid." Typical drug review includes pre-clinical studies followed by increasingly large clinical studies, culminating in pivotal, larger-scale studies to demonstrate the safety and efficacy of the product that become the focus of the approval, i.e., the regular pyramid (pre-clinical on top, phase III clinical trials on the bottom . In contrast, biosimilar product development is envisioned to be characterized as spending a bulk of the resources up front, characterizing the innovator's product and the biosimilar (i.e., the top of the pyramid to lead to smaller clinical studies to demonstrate similarity or test for immunogenicity or other elements that require testing, not duplicating the safety and efficacy testing that was already conducted by the innovator.
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