|May 2013, Volume XXIII, No. 3|
Regulatory & Legislative Highlights
by Deepen Joshi, Sunovion Pharmaceuticals
The FDA announced that it has cleared a test to help manage potential organ rejection in kidney transplant patients. The test, called QMS Everolimus Immunoassay, monitors the blood level of everolimus, a drug that helps prevent rejection in kidney transplants. The immunoassay is manufactured by Waltham-based Thermo Fisher Scientific.
Everolimus, marketed under the trade name Zortress, was approved by FDA for use in adult kidney transplant patients who are at low-to-moderate immunologic risk. It is marketed by Novartis.
Transplant patients are routinely given drugs that suppress the immune system, such as a regimen containing everolimus, cyclosporine, basiliximab, and corticosteroids. These drugs help prevent organ rejection, which occurs when the body's immune system attacks and destroys a transplanted organ.
More than 87,000 patients are awaiting a kidney transplant in the United States, according to the Health Resources and Services Administration's Organ Procurement and Transplantation Network. (Source: 11 February, 2011, FDA Website)
The FDA approved the Selenia Dimensions System, the first X-ray mammography device that provides three-dimensional (3-D) images of the breast for breast cancer screening and diagnosis. The Selenia Dimensions System is marketed by Bedford-based Hologic.
A mammogram is a safe, low-dose X-ray of the breast that is the best tool for early detection of breast cancer. The Selenia Dimensions System, an upgrade to Hologic's existing FDA-approved 2-D system, can provide 2-D and 3-D X-ray images of the breasts. The 3-D images may help physicians more accurately detect and diagnose breast cancer.
The National Cancer Institute recommends women ages 40 and older have a mammogram every one to two years. Nearly 40 million mammograms are performed each year in the United States. (Source: FDA Website, 11 February, 2011)
The FDA approved Corifact, the first product intended to prevent bleeding in people with the rare genetic defect congenital Factor XIII deficiency. Patients with congenital Factor XIII deficiency do not make enough Factor XIII, a substance that circulates in the blood and is important for normal clotting. Without treatment, people with the condition are at risk for life-threatening bleeding.
Congenital Factor XIII deficiency is rare and affects 1 out of every 3 million to 5 million people in the United States. The deficiency may lead to soft tissue bruising, mucosal bleeding and fatal intracranial bleeding. Newborns with Factor XIII deficiency may have umbilical cord bleeding.
Corifact received orphan-drug designation by the FDA because it is intended for use in a rare disease or condition. It was approved for marketing under the FDA's accelerated approval regulations that require an on-going study to demonstrate that patients actually receive the clinical benefit predicted by the data obtained so far.
Corifact is made from the pooled plasma of healthy donors and is manufactured by CSL Behring of Marburg, Germany. (Source: FDA Website, 17 February, 2011)
The FDA approved Edarbi tablets (azilsartan medoxomil) to treat high blood pressure (hypertension) in adults. Edarbi is an angiotensin II receptor blocker (ARB) that lowers blood pressure by blocking the action of angiotensin II, a vasopressor hormone. It is manufactured by Takeda Pharmaceutical North America of Deerfield, Illinois.
Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps. If blood pressure rises and stays high over time, it can damage the body in many ways. Nearly 1 in 3 adults in the United States has high blood pressure, which increases the risks of stroke, heart failure, heart attack, kidney failure, and death. Data from clinical studies showed Edarbi to be more effective in lowering 24-hour blood pressure compared with two other FDA-approved hypertension drugs, Diovan (valsartan) and Benicar (olmesartan).
Edarbi has a boxed warning that says the use of the drug should be avoided in pregnant women because use of the drug during the second or third trimester can cause injury and even death in the developing fetus. If a woman becomes pregnant while using the drug, it should be discontinued as soon as possible. (Source: FDA Website, 25 February, 2011)
The FDA approved roflumilast, a pill taken daily to decrease the frequency of flare-ups or worsening of symptoms from severe chronic obstructive pulmonary disease (COPD), a serious lung disease that makes breathing difficult. Symptoms of COPD can include breathlessness, chronic cough and excessive phlegm. A flare-up can last up to several weeks and result in lung function decline, increased risk of death, and may be associated with severe anxiety.
Cigarette smoking is the leading cause of COPD, according to the National Heart, Lung, and Blood Institute. COPD is the fourth leading cause of death in the United States.
Roflumilast, a new drug class for the treatment of COPD, is an inhibitor of an enzyme called phosphodiesterase type 4 (PDE-4). It is indicated for people with severe COPD to treat the symptoms of cough and excess mucus linked to bronchitis. Roflumilast is not intended to treat another form of COPD which involves primary emphysema. The drug marketed by St. Louis-based Forest Pharmaceuticals, a subsidiary of Forest Laboratories. (Source: FDA Website, 1 March, 2011)
New data suggest that the drug Topamax (topiramate) and its generic versions increase the risk for the birth defects cleft lip and cleft palate in babies born to women who use the medication during pregnancy. Topiramate is approved to treat certain types of seizures in people who have epilepsy; it is also approved to prevent migraine headaches.
Cleft lip and cleft palate, collectively called oral clefts, are birth defects that occur when parts of the lip or palate do not completely fuse together early in the first trimester of pregnancy, a time when many women do not know they are pregnant. The defects range from a small notch in the lip to a groove that runs into the roof of the mouth and nose, possibly leading to problems with eating, talking, and to ear infections. Surgery often is performed to close the lip and palate and most children do well after treatment.
The patient medication guide and prescribing information for Topamax and generic topiramate will be updated with the new information. (Source: FDA Website, 4 March, 2011)
The FDA approved Gadavist (gadobutrol), a gadolinium-based contrast agent, for use in patients undergoing magnetic resonance imaging (MRI) of the central nervous system. Gadavist provides contrast-enhanced imaging of the central nervous system, helping to detect and visualize lesions that disrupt the cell barrier that normally separates the brain from the blood stream. It also helps to detect and visualize abnormal blood supply and circulation of the central nervous system.
Gadavist is the sixth gadolinium-based contrast agent (GBCA) approved by the FDA for use in patients undergoing magnetic resonance imaging of the central nervous system. It is manufactured by Bayer Pharmaceuticals. (Source: FDA Website, 15 March, 2011)
The FDA and the European Medicines Agency (EMA) have launched a new pilot program that will allow parallel evaluation of relevant development and manufacturing data components, known as Quality by Design (QbD), of new drug marketing applications that are submitted to both agencies.
The parallel evaluation within this voluntary pilot program means that reviewers from both agencies will separately assess the quality/chemistry, manufacturing and control (CMC) section of the new drug applications (NDAs) submitted to the FDA and marketing authorization applications (MAAs) submitted to the EMA. However, there will be regular communication and consultation between European regulators and their US colleagues throughout the review process relevant to QbD aspects of the applications.
QbD in pharmaceuticals involves designing and developing pharmaceutical formulations and manufacturing processes to help ensure product manufacturing quality. Several guidelines have been developed by the International Conference on Harmonisation (ICH) to harmonize and facilitate the implementation of QbD. This pilot program began out of concern that certain ICH guidelines were being interpreted differently in Europe and the United States.
This pilot program applies to NDAs and MAAs, some supplements, and CMC meeting requests that include QbD elements submitted to both agencies at about the same time. The pilot will only include chemical entities and not biologically-derived products. Review of QbD applications does not change statutory deadlines. (Source: FDA Website, 16 March, 2011)
FDA Approves Zostavax Vaccine to Prevent Shingles in Younger Individuals
In the United States, shingles affects approximately 200,000 healthy people between the ages of 50 and 59 each year. It is a disease caused by the varicella-zoster virus, which is a virus in the herpes family and the same virus that causes chickenpox. After an attack of chickenpox, the virus lies dormant in certain nerves in the body. For reasons that are not fully understood, the virus can reappear in the form of shingles, more commonly in people with weakened immune systems and with aging. (Source: FDA Website, 24 March, 2011)
The FDA has approved vandetanib to treat adult patients with late-stage (metastatic) medullary thyroid cancer who are ineligible for surgery and who have disease that is growing or causing symptoms. The drug is marketed by AstraZeneca Pharmaceuticals LP of Wilmington, Delaware.
Thyroid cancer is a cancerous growth of the thyroid gland, which is located in the neck. Medullary thyroid cancer involves specific types of cells that are found in the thyroid gland and can occur spontaneously, or be part of a genetic syndrome.
About 44,600 new thyroid cancer cases were diagnosed in the United States during 2010, and about 1,690 people died from the disease, according to the National Cancer Institute. Medullary thyroid cancer is estimated to represent 3 to 5 percent of all thyroid cancer; its estimated incidence in the United States for 2010 is about 1,300 to 2,200 patients, making it one of the rarer forms of thyroid cancer.
Vandetanib targets medullary thyroid cancer's ability to grow and expand. There are currently no FDA-approved treatments for this type of cancer. Vandetanib is administered orally on a daily basis.
Vandetanib was shown to affect the electrical activity of the heart, which in some cases can cause irregular heart beats that could lead to death. Vandetanib is being approved with a Risk Evaluation and Mitigation Strategy (REMS) to inform health care professionals about these serious heart-related risks. (Source: FDA Website, 16 April, 2011)
The FDA approved Horizant Extended Release Tablets (gabapentin enacarbil), a once-daily treatment for moderate-to-severe restless legs syndrome (RLS). Horizant was developed by GlaxoSmithKline of Research Triangle Park, North Carolina and Xenoport of Santa Clara, California.
RLS is a disorder that causes a strong urge to move the legs. This urge often occurs with unpleasant feelings in the legs. People who have RLS describe feeling pulling, itching, tingling, burning, or aching in their legs, and moving the legs temporarily relieves these feelings. The urge to move often happens when a person is inactive, and the symptoms typically are worse in the evening and early morning.
Horizant will be dispensed with an FDA-approved Medication Guide that explains the drug's uses and risks. Horizant may cause drowsiness and dizziness and can impair a person's ability to drive or operate complex machinery.
Horizant contains gabapentin enacarbil that becomes gabapentin, a drug used to treat seizures in people with epilepsy, when absorbed into the body. All drugs used to treat epilepsy carry warnings that they may cause suicidal thoughts and actions in a small number of people. Horizant will have the same warning. (Source: FDA Website, 7 April, 2011)
The FDA allowed marketing of the first test to help diagnose people with signs and symptoms of dengue fever or dengue hemorrhagic fever, a leading cause of illness and death in the tropics and subtropics. The dengue virus is transmitted to humans by the bite of an infected Aedes mosquito. As many as 100 million people worldwide are infected by the virus each year, according to the Centers for Disease Control and Prevention (CDC).
The DENV Detect IgM Capture ELISA test detects antibodies to dengue virus in blood samples from patients who have signs and symptoms of dengue. The test will be available for use in clinical laboratories and will assist in the diagnosis of dengue, which can improve patient care and management.
There are currently no FDA-cleared or approved tests for direct detection of dengue virus. The DENV Detect IgM Capture ELISA test is based on technology patented by the CDC and manufactured by Seattle-based Inbios Inc.
This new test shows cross-reaction with other closely related viruses such as those that cause West Nile disease. However, in most patient testing situations found in the United States, a positive test result in a patient with signs or symptoms consistent with dengue should be considered presumptive evidence of dengue. (Source: FDA Website, 8 April, 2011)
The FDA has approved Genentech's Actemra (tocilizumab), given alone or in combination with methotrexate, for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in children ages 2 years and older.
SJIA, or Still's disease, is a rare, potentially life-threatening disorder in children that causes severe inflammation throughout the body. Actemra is an interleukin-6 receptor blocker approved by the FDA for treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to other approved therapies.
Actemra carries a Boxed Warning for serious infections. Patients treated with Actemra who develop a serious infection should stop Actemra treatment until the infection is controlled. A Boxed Warning is a brief, concise summary of the information that is critical for a prescriber to be aware of, including any restriction on distribution or use, which is included in a black box at the beginning of the drug label. (Source: FDA Website,15 April, 2011)
The FDA approved the NovoTTF-100A System, a new device to treat adults with glioblastoma multiforme (GBM) that recurs or progresses after receiving chemotherapy and radiation therapy. The NovoTTF-100A System is made by Novocure of Portsmouth, New Hampshire.
Brain tumors are the growth of abnormal cells in the brain tissue. According to the National Cancer Institute, each year about 19,000 people in the United States are diagnosed with primary brain cancers. In 2010, there were 13,140 deaths from brain and other nervous system cancers in the United States. GBM is the most common primary brain cancer. The brain tumor is highly resistant to standard treatments such as surgery, radiation and chemotherapy.
When using the NovoTTF-100A System, a health care professional places electrodes on the surface of the patient's scalp to deliver low-intensity, changing electrical fields called "tumor treatment fields" (TTFs) to the tumor site. The unique shape and electrical characteristics of dividing tumor cells make them susceptible to damage when exposed to TTF, which could stop tumor growth.
The device is portable and can be powered with batteries or plugged into an electrical outlet. Patients can use the device at home, allowing them to continue their normal daily activities. (Source: FDA Website,15 April, 2011)
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