Zytiga (abiraterone acetate) Approved For Treating Late-stage Prostate Cancer

The U.S. Food and Drug Administration today approved Zytiga (abiraterone acetate) in combination with prednisone (a steroid) to treat patients with late-stage (metastatic) castration-resistant prostate cancer who have received prior docetaxel (chemotherapy).

In prostate cancer, the male sex hormone testosterone stimulates prostate tumors to grow. Drugs or surgery are used to reduce testosterone production or to block testosterone’s effects. However, sometimes prostate cancer can continue to grow even when testosterone levels are low. Men with these cancers are said to have castration-resistant prostate cancer. 

Zytiga is a pill that targets a protein called cytochrome P450 17A1 (CYP17A1) which plays an important role in the production of testosterone. The drug works by decreasing the production of this hormone that would stimulate cancer cells to continue growing.

The application was reviewed under the FDA’s priority review program, which provides for an expedited six-month review for drugs that may offer major advances in treatment, or provide a treatment when no adequate therapy exists. Zytiga is being approved ahead of the product’s June 20, 2011 regulatory goal date.

“Zytiga prolonged the lives of men with late-stage prostate cancer who had received prior treatments and had few available therapeutic options,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research.

Zytiga’s safety and effectiveness were established in a clinical study of 1,195 patients with late-stage castration-resistant prostate cancer who had received prior treatment with docetaxel chemotherapy. Patients received either Zytiga once daily in combination with prednisone two times a day or a placebo (sugar pill) twice daily in combination with prednisone.

The study was designed to measure overall survival, the length of time from when the treatment started until a patient's death. Patients who received the Zytiga and prednisone combination had a median overall survival of 14.8 months compared to 10.9 months for patients receiving the placebo and prednisone combination.

The most commonly reported side effects in patients receiving Zytiga included joint swelling or discomfort, low levels of potassium in the blood, fluid retention (usually of the legs and feet), muscle discomfort, hot flashes, diarrhea, urinary tract infection, cough, high blood pressure, heartbeat disorders, urinary frequency, increased nighttime urination, upset stomach or indigestion and upper respiratory tract infection.

Zytiga is marketed by Horsham, Pa.-based Centocor Ortho Biotech, Inc.

The press release could be found here.

Afinitor (Everolimus) Approved By FDA To Treat Rare Type Of Pancreatic Cancer

FDA approves new treatment for rare type of pancreatic cancer

On Thursday, the U.S. Food and Drug Administration approved Afinitor (everolimus) to treat patients with progressive neuroendocrine tumors located in the pancreas (PNET) that cannot be removed by surgery or that have spread to other parts of the body (metastatic). 

Neuroendocrine tumors found in the pancreas are slow-growing and rare. It is estimated that there are fewer than 1,000 new cases in the United States each year.

“Patients with this cancer have few effective treatment options,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. “Afinitor has demonstrated the ability to slow the growth and spread of neuroendocrine tumors of the pancreas.”

The safety and effectiveness of Afinitor was established a clinical trial in 410 patients with metastatic (late-stage) or locally advanced (disease that could not be removed with surgery) disease. Patients in the study were selected to receive Afinitor or placebo (sugar pill). The trial was designed to measure the length of time a patient lived before their disease spread or worsened (progression-free survival).

In patients treated with Afinitor, the median length of time they lived without the cancer spreading or worsening was 11 months compared with 4.6 months in patients who received placebo. Patients who received placebo were able to receive Afinitor if their disease worsened. 

In patients treated with Afinitor for neuroendocrine pancreatic tumors, the most commonly reported side effects included inflammation of the mouth (stomatitis), rash, diarrhea, fatigue, swelling (edema), stomach (abdominal) pain, nausea, fever, and headache.

Afinitor is also approved to treat patients with kidney cancer (advanced renal cell carcinoma) after they fail treatment with Sutent (sunitinib) or Nexavar (sorafenib); and  patients with subependymal giant cell astrocytoma (a type of brain cancer) associated with tuberous sclerosis (a disease that causes tumors in various parts of the body), who cannot be treated by surgery.  

Afinitor has another trade name, Zortress, and is approved to treat certain adult patients to prevent organ rejection after a kidney transplant. Zortress has a different safety profile in these patients. 

Afinitor is marketed by East Hanover, N.J.-based Novartis.

For more information:

FDA: Office of Oncology Drug Products

FDA: Approved Drugs: Questions and Answers

NCI: Pancreatic Cancer

Abstral (Fentanyl) Transmucosal Tablets Approved By FDA For Alleviating Breakthrough Pain In Adult Cancer Patients.

FDA, Food and Drug Administration  has approved Abstral (fentanyl) transmucosal tablets for alleviating breakthrough pain in adult cancer patients. Breakthrough pain is pain that comes on suddenly for short periods of time and is not alleviated by a patient’s normal pain management plan. These patients are considered opioid tolerant because of their current opioid medication use.

“This is an important step for patients with cancer pain to have options for the treatment of their breakthrough pain,” said John Jenkins, M.D., director of FDA’s Office of New Drugs in the Center for Drug Evaluation and Research.

Only health care professionals skilled in the use of Schedule II opioids to treat pain should prescribe this drug product. 
Transmucosal drugs are absorbed through soft surfaces in the mouth like Cheeks, Gums,  Tongue, and also nasal passages and throat.
Abstral is available only through a Risk Evaluation and Mitigation Strategy (REMS) program, which is intended to minimize the risk of misuse, abuse, addiction and overdose.  Under this program, pharmacies, distributors, and health care professionals who prescribe to outpatients are required to enroll in the program to prescribe, dispense and distribute this product.
The safety of Abstral was evaluated in 311 opioid-tolerant cancer patients with breakthrough pain.  Two hundred and seventy of these patients were treated in multiple-dose studies. The duration of therapy for patients in multiple-dose studies ranged from 1-405 days with an average duration of 131 days and with 44 patients treated for at least 12 months.

FDA PRESS RELEASE

For Immediate Release: Jan 7, 2011
Media Inquiries: Shelly Burgess, 301-796-4651, shelly.burgess@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA approves opioid analgesic to help cancer patients manage pain
Enrollment in REMS program required for health care professionals

The U.S. Food and Drug Administration today approved Abstral (fentanyl) transmucosal tablets to manage breakthrough pain for adults with cancer.  Fentanyl immediate-release transmucosal medications are administered on the soft surfaces of the mouth (inside of the cheek, gums, tongue), or the nasal passages or throat where they dissolve and are absorbed.

“This is an important step for patients with cancer pain to have options for the treatment of their breakthrough pain,” said John Jenkins, M.D., director of FDA’s Office of New Drugs in the Center for Drug Evaluation and Research.

Abstral is indicated for the management of breakthrough pain in patients with cancer, ages 18 years and older, who already use opioid pain medication around the clock and who need and are able to safely use high doses of an additional opioid medicine.  Breakthrough pain is pain that comes on suddenly for short periods of time and is not alleviated by a patient’s normal pain management plan. These patients are considered opioid tolerant because of their current opioid medication use.  Only health care professionals skilled in the use of Schedule II opioids to treat pain should prescribe this drug product.

Abstral is available only through a Risk Evaluation and Mitigation Strategy (REMS) program, which is intended to minimize the risk of misuse, abuse, addiction and overdose.  Under this program, pharmacies, distributors, and health care professionals who prescribe to outpatients are required to enroll in the program to prescribe, dispense and distribute this product.  FDA has standardized key components of the REMS program to facilitate the adoption of a single shared system. These components include the REMS document, the Patient-Prescriber Agreement, and the enrollment form. These components can be used by all sponsors of immediate release transmucosal fentanyl products to develop individual REMS programs  such as the program approved for Abstral.  FDA has also directed the sponsors of this class of products to work together on a single shared system to implement the REMS.

“This approval is also a significant step toward reducing the burden on the health care system of implementing REMS programs,” added Dr. Jenkins. “When fully implemented, FDA expects that prescribers, pharmacies, and distributors of all immediate release transmucosal fentanyl products will be able to use standardized materials and a single shared system to implement the REMS.”

The safety of Abstral was evaluated in 311 opioid-tolerant cancer patients with breakthrough pain.  Two hundred and seventy of these patients were treated in multiple-dose studies. The duration of therapy for patients in multiple-dose studies ranged from 1-405 days with an average duration of 131 days and with 44 patients treated for at least 12 months.

Common adverse reactions include nausea, constipation, drowsiness and headache. Serious adverse events, including deaths, have been reported in patients with other immediate-release transmucosal fentanyl products. The deaths occurred as a result of improper patient selection and/or improper dosing.

Consumers and health care professionals are encouraged to report adverse side effects or medication errors from the use of Abstral to the FDA's MedWatch Adverse Event Reporting program at www.fda.gov/MedWatch or by calling 800-332-1088.


Abstral is manufactured by ProStraken Inc., based in Bedminster, N.J.

Amgen's XGEVA™ (denosumab), Gets FDA Approval for Fractures in Cancer Treatment

THOUSAND OAKS, Calif., (Nov. 18, 2010) /PRNewswire/ — Amgen Inc. (NASDAQ: AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved XGEVA™ (denosumab), the first and only RANK Ligand inhibitor for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. XGEVA was approved following a 6 month priority review by the FDA, a designation reserved for drugs that offer major advances in treatment or provide a treatment where no adequate therapy exists. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma.

“Today’s approval of XGEVA illustrates what is possible when scientific innovation, commitment and investment come together to advance medicine,” said Kevin Sharer, chairman and chief executive officer of Amgen. “A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating. We are pleased to offer this new advance to patients and their healthcare providers.”

Bone metastases, the spread of cancer to the bones, are a serious concern for patients with advanced cancer and present a considerable burden to the healthcare system. Weakened bones due to metastases can lead to fractures and compression of the spinal cord and necessitate procedures like major surgery and radiation, designed to prevent or manage bone complications. The primary goal of treatment for bone metastases is to prevent the occurrence of debilitating and costly bone complications, which can disrupt a patient’s life and cause disability, pain and hospitalization.

“As many as 3 out of 4 patients with advanced prostate, lung, and breast cancer will experience spread to their bones. Despite the availability of current treatments, a significant proportion of these patients still experience bone complications or are not candidates for existing treatment,” said David H. Henry, M.D., clinical professor of medicine, and vice chair, Department of Medicine, Pennsylvania Hospital, University of Pennsylvania Healthcare System. “Based on the compelling science and robust clinical evidence seen with XGEVA, I expect this new option to quickly become a mainstay of cancer care and to play an important role in reducing the incidence of debilitating bone complications in patients with advanced cancer.”

The RANK Ligand pathway, first discovered by Amgen scientists in the mid-1990s, is believed to play a central role in cancer-induced bone destruction, regardless of cancer type. XGEVA is a fully human monoclonal antibody that binds to RANK Ligand, a protein essential for the formation, function and survival of osteoclasts (the cells that break down bone). XGEVA prevents RANK Ligand from activating its receptor, RANK on the surface of osteoclasts, thereby decreasing bone destruction.

XGEVA Clinical Trial Experience

The FDA approval of XGEVA is based on the results of three pivotal, Phase 3 head-to-head trials that evaluated XGEVA delivered every four weeks as a 120 mg subcutaneous injection versus Zometa® (zoledronic acid) delivered every four weeks via a 15-minute intravenous infusion, adjusted for kidney function per the labeled instructions. The clinical program for XGEVA spanned more than 50 tumor types in over 5,700 patients. In the Phase 3 trials, XGEVA demonstrated a clinically meaningful improvement in preventing SREs compared to Zometa. Specifically, in patients with breast or prostate cancer and bone metastases, XGEVA was superior to Zometa in reducing the risk of SREs. In patients with bone metastasis due to other solid tumors or bone lesions due to multiple myeloma, XGEVA was noninferior (trending towards superiority) to Zometa in reducing the risk of SREs. Superiority was also seen in the integrated analysis of the Phase 3 studies.

Overall rates of adverse events and serious adverse events were generally similar between XGEVA and Zometa. Osteonecrosis of the jaw (ONJ) was infrequent, with no statistically significant difference between treatment arms. Hypocalcemia was more frequent in the XGEVA arm. Overall survival and progression-free survival were similar between arms in all three trials.

“As many as 70 percent of patients with prostate cancer that have metastasized to the bone are not currently receiving therapy to prevent complications from these bone metastases. This may be secondary to urologists lacking comfort or facilities to provide infusion treatment,” said Neal D. Shore, M.D., FACS, medical director, Carolina Urologic Research Center. “XGEVA could provide increased treatment care options and accessibility for urologist’s who treat advanced prostate cancer; as XGEVA is administered as a subcutaneous injection on a monthly basis. Also, XGEVA does not require dose adjustment for changes in renal function.”

ECONOMIC IMPACT OF SREs

The total economic burden of patients with bone metastases in the U.S. alone estimated to be $12.6 billion annually.ⁱ Patients who experience an SRE as a result of bone metastases incur significantly higher medical costs compared with those who do not experience such events.^{ii iii iv} In addition, once patients experience an SRE, the risk of a subsequent SRE is increased. The costs of SREs vary by type and severity, ranging from relatively low costs for minor fractures to high cost events like spinal cord compression associated with hospitalization. Studies have shown that the costs of treating SREs are a significant cost burden.

XGEVA is an innovative therapy that significantly reduces debilitating and costly SREs. This can result in cost offsets due to the reduced incidence of SREs and related medical costs. XGEVA will cost $1,650 monthly based on wholesale acquisition cost.

XGEVA FIRST STEP™ COUPON PROGRAM

Amgen is committed to supporting patient access to important medicines through innovative programs including our newly established commercial co-pay program for XGEVA, financial support to independent third party co-pay foundations, and the Safety Net Foundation, which provides free products to uninsured patients who qualify. The XGEVA FIRST STEP™ Coupon Program is a landmark program among oncology commercial co-pay programs, as it is the first program under the medical benefit with no income eligibility requirement. The program is intended to provide assistance to eligible patients who need help meeting their deductible, co-insurance, and/or co-payment requirements under the medical benefit for XGEVA. Under this program, eligible patients will incur no out of pocket costs for their initial XGEVA injection and pay a maximum of $25 for subsequent injections.

XGEVA Regulatory Status

Amgen has also submitted marketing applications for XGEVA in the European Union, Australia, Canada and Switzerland. In Japan, Amgen is working with its licensing partner, Daiichi-Sankyo Company, Limited and a marketing application was submitted in August.

XGEVA Important Safety Information

XGEVA can cause severe hypocalcemia. Correct pre-existing hypocalcemia prior to XGEVA treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.

Osteonecrosis of the jaw can occur in patients receiving XGEVA. Patients who are suspected of having or who develop ONJ while on XGEVA should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.

The most common adverse reactions in patients receiving XGEVA were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction in patients receiving XGEVA was dyspnea. The most common adverse reactions resulting in discontinuation of XGEVA were osteonecrosis and hypocalcemia. Please visit www.amgen.com for full prescribing information.

Denosumab is also marketed as Prolia™ in other indications.

Bone Metastases and SREs: Prevalence and Impact

Bone metastases occur in more than 1.5 million patients with cancer worldwide and are most commonly associated with cancers of the prostate, lung, and breast, with incidence rates as high as 75 percent of patients with metastatic disease.^v

Approximately 50-70 percent of cancer patients with bone metastases will experience debilitating SREs.^{vi vii viii} Events considered to be SREs include fractures, spinal cord compression, and severe bone pain that may require surgery or radiation.^ix Such events can profoundly disrupt a patient’s life and can cause disability and pain.^{x xi xii}

Denosumab and Amgen's Research in Bone Biology

The denosumab development program demonstrates Amgen's commitment to researching and delivering pioneering medicines to patients with unmet medical needs. Amgen is studying denosumab in numerous tumor types across the spectrum of cancer-related bone diseases. Over 11,000 patients have been enrolled in the denosumab oncology clinical trials. In addition to this newly approved indication, XGEVA is also being investigated for its potential to delay bone metastases in prostate and breast cancer.