An advisory panel on Wednesday recommended that U.S. health regulators reject the use of Amgen Inc’s drug Xgeva to delay the spread of prostate cancer to the bone, dimming the chance of a wider use for one of the company’s key growth drivers.

The outside advisers to the Food and Drug Administration voted 12-to-1 that the benefits of the injectable drug, known chemically as denosumab, did not outweigh the risk of developing a jawbone-destroying condition.

Xgeva is already approved to prevent fractures and related problems in advanced prostate cancer that has spread to the bone, and the company is seeking additional approval for use of the drug to delay or prevent the spread.

The drug did delay the spread of cancer to the bone by a little longer than four months in a clinical trial of 1,432 men with prostate cancer who had stopped responding to hormone therapy.

But about one in 15 men who took the drug developed osteonecrosis of the jaw, a severe side effect in which jawbone tissue dies, exposing the bone. that rate is far higher than has been seen with widely used osteoporosis drugs.

“If you ask a patient, ‘Do you want to delay your disease by five minutes, but get significant toxicities?’ I think that would give them pause,” said panel member Maha Hussain, a professor of medicine in the hematology and oncology division at the University of Michigan.

The FDA usually follows the recommendations of its expert panels and will make a final decision by April 26.

Most analysts had expected the unfavorable panel vote because the FDA had questioned whether delaying the spread of cancer to the bone was a meaningful benefit to patients given that the drug did not help men live longer or delay the growth of prostate cancer..

“We believe the panel recommendation reinforces the FDA’s view, which has been consistently negative, and approval is unlikely,” said Geoff Meacham, analyst at JP Morgan, in a research note.

However, he said the risk of a rejection of wider approval for Xgeva had only a modest risk to his long-term revenue estimates for Amgen, the world’s largest biotechnology company.

Benefits to patients?

Xgeva and a related osteoporosis drug Prolia are seen as among the most important growth drivers for Amgen and are expected to help offset declining sales of the anemia drugs that had been the company’s backbone.

In the fourth quarter of 2011, sales of Xgeva rose to $134 million from $100 million in the prior quarter, and it is expected to eventually become a $1 billion-a-year drug.

The company said the new use for Xgeva would be targeted at about 50,000 men in the United States at that advanced stage of the disease.

Panel members questioned whether using the drug earlier actually benefited patients, as many did not have symptoms of the disease, but would suffer any drug-related side effects.

However, the patient representative on the panel voted in favor of approval.

“There isn’t a treatment that a man with prostate cancer gets that doesn’t have devastating effects on his masculinity and his quality of life,” said James Kiefert, of Olympia, Washington. “In my opinion, the men who would be candidates for this treatment would be standing up and cheering another option for them.”

His views echoed the favorable comments of several urologists, who testified in favor of the drug during the public hearing.

Amgen said Xgeva provided a meaningful benefit to prostate cancer patients by preventing the spread of their disease to the bones, which is not uncommon.

“We look forward to further discussions with the FDA as they continue to review our application,” the company said in a statement after the vote.

If Xgeva gains wider approval, it would be the first drug to delay the spread of prostate cancer to the bone, Amgen said.

Amgen said it was also testing Xgeva in other cancers, including breast and lung cancer and the blood cancer multiple myeloma.

Mon 2:36 pm by Olivia D'Orazio

Novartis Pharma’s (NYSE:NVS) SMC021 drug, intended for the treatment of post-menopause osteoporosis, failed to meet the endpoints of phase three study, Study 2303, according to its development partner, Unigene Laboratories (OTCBB:UGNE).

The placebo-controlled study was to assess the safety and efficacy of the drug, an oral formulation of calcitonin, which used Emisphere Technologies’ (OTCBB:EMIS) proprietary oral delivery technology, Unigene said.

The results of the study showed that the drug failed to demonstrate a significant difference between treatment groups at the end of the three-year study. Novartis said the only statistically significant result was an increase in the lumbar spine bone mineral density in the group treated with SMC021, compared to the placebo arm.

However, the data did show a positive safety profile for the drug, Novartis said.

Osteoporosis is a disease that causes bones to become brittle, making them more likely to break. it is common in men and women over the age of 50, and, since it has no outwardly signs or symptoms, is usually only diagnosed following a bone fracture.

The prevalence of the condition among post-menopausal women is growing, and osteoporosis now accounts for more days spent in the hospital than many other diseases, including diabetes, heart attack and breast cancer, in women over 45 years of age.

Calcitonin is a natural hormone that has been used to treat bone diseases including osteoporosis for over 25 years. Oral calcitonin might replace injections, and challenge nasal delivery of calcitonin.

Unigene president and CEO, Ashleigh Palmer, commented: “While we would have preferred positive results from this Phase 3 trial, the outcome has very limited impact on Unigene’s successful turnaround strategy.

“Unigene’s own oral formulation of salmon calcitonin reached Phase 3 statistical significance for its primary endpoint as presented in detail at the American Society of Bone and Mineral Research in September.

“Although today’s news reduces the likelihood of near-term royalties under our manufacturing license with Novartis, it ironically now places Unigene in an exceptionally strong leadership position with respect to our oral peptide drug delivery platform.”

Under the terms of Novartis’ agreement with Unigene, signed in April 2004, Unigene would receive a total of $18.7 million, before royalties, in exchange for the worldwide licensing rights to manufacture calcitonin using Unigene’s patented peptide production process. Unigene is also entitled to receive single-digit royalties on net sales of any existing or future Novartis product that uses this technology.

To date, Novartis has paid $13.7 million in milestone payments to Unigene under this agreement.

In new York, Novartis shares fell 0.77 percent to $55.22, while Unigene shares on the OTC Bulletin Board sank nine percent to $0.91, as of 1:43 pm EDT.

Meanwhile, Emisphere shares, also on the OTC Bulletin Board, plunged 76.1 percent, or $1.21 per share, to $0.38 as of 1:31 pm EDT.

Yesterday, French newspaper Libération reported that the European Medicines Agency (EMA) in London has set its sights on Servier as well—initially for problems around strontium ranelate, an osteoporosis drug marketed by Servier in France under the name Protelos. an estimated 390,000 French women in France have taken the drug during the last 4 years.

Dominique Maraninchi, head of the French regulatory agency AFSSAPS, confirmed EMA’s worries in a telephone interview with ScienceInsider. in November 2007, EMA’s Pharmacovigilance Working Party issued a warning that Protelos could cause severe and potentially fatal skin rashes known as Drug Reaction with Eosinophilia and Systemic Symptoms, and ordered Servier to correct “flaws” in its system to keep track of such adverse events, Maraninchi says.

EMA asked AFSSAPS to carry out an inspection in December 2009 to ensure Servier had followed up. that inspection revealed other “critical and major findings,” this time with Servier’s manufacturing process, and raised concerns over all of the company’s drugs, says Maraninchi. as a result, Servier was ordered to submit information on all of its medicines to EMA, whether authorized for marketing by EMA itself or by national agencies.

EMA eventually concluded that the benefit-risk balance remained positive for Servier’s drugs, but it instructed the company to provide extra product information for some of them, an EMA spokesperson says. AFSSAPS carried out a second inspection in July of this year and will present its findings by the end of this month.

On Tuesday, reports in the newspapers Le Figaro and Libération also cast doubts on Servier’s integrity when it applied for regulatory approval for Mediator in 1973. the papers quoted from the court testimony of retired neurosurgeon Jean Charpentier, now 81, who prepared the regulatory file at the time. Charpentier, who started working for Servier in 1968, reportedly told the judges that clinical trials had shown Mediator to be a powerful appetite-suppressant, but that this was downplayed in his report to get Mediator approved as an antidiabetic drug. (Diabetes was “an infinitely more profitable choice” than weight loss for pharmaceutical companies, said Charpentier.)

the report also didn’t mention that Mediator is an amphetamine derivative, Charpentier said in his testimony. “The word amphetamine was to be avoided,” he said.

Jacques Duhault, 78, a pharmacist who headed the company’s diabetes and obesity lab in the 1960s, told the judges he regretted that Servier didn’t pull Mediator as a precautionary measure in 1999, Libération reported. his studies described the drug as a “powerful appetite suppressant.” in January 1969, he said that the drug, then known by its code name S992, “causes almost total anorexia from the first day.”

Servier has dismissed all of the allegations. in press statements, the company has condemned the breach of judicial secrecy over the Mediator testimonies, reaffirmed that it had “deceived neither the health authorities nor patients,” and denied that any of Charpentier’s studies had been tampered with.

But as it affects younger women, the issue of pregnancy can be a matter of particular concern.

As the menopause usually occurs at around the age of fifty, specialists use the term early menopause or rather “premature ovarian dysfunction” when it occurs before the age of 40.

When menopause occurs, periods cease. Sometimes it engenders menstrual cycle problems, including hot flushes, mood swings, vaginal dryness, etc.

And according to medical experts, women should consult with their doctors as soon as they start experiencing some of the symptoms.

While early menopause can be brought on by treatment for certain types of cancer, chromosome anomalies can also be to blame, as can auto-immune diseases.

Smoking too has been shown to be a risk factor. however, it is often the case that the precise cause of early menopause remains unknown.

To improve the patient’s quality of life, but also to avoid the risks associated with the menopause, and osteoporosis in particular, appropriate treatment may be offered.

So speak to your doctor.

Bone loss drugs in the class of bisphosphonates have, again, been linked to bone fractures of the femur (thigh bone). Web MD said that a recent, large review of over 200,000 post-menopausal women found that those taking bisphosphonates—drugs sold under the names Fosamax, Fosamax Plus D, Actonel, Actonel with Calcium, Boniva, Atelvia, and Reclast, as well as generics—for over five years experienced a two-fold likelihood of suffering fractures, versus women taking these drugs for briefer periods.

Fractures occurred in about one of every 1,000 women who took bisphosphonates for five years or more, one of the researchers told WebMD. The study appears in the February 23rd issue of the Journal of the American Medical Association.According to recent studies, about half of all women over the age of 50 will suffer a bone loss-related fracture, and about one in every five of these women will die within a year, noted WebMD, noting that bisphosphonates are taking by millions of patients in the U.S. In addition to their use in preventing osteoporosis fractures, bisphosphonates also help to reduce hip, spine, and other fractures related to weakened bones.

Despite this, reports began emerging in recent years about long-term bisphosphonate use and femur fractures, prompting the FDA to mandate a label change on the medication to include a warning of “possible risk of atypical thigh bone fracture” in long-term users, said WebMD. “While it is not clear whether bisphosphonates are the cause, atypical femur fractures … have been predominantly reported in patients taking bisphosphonates,” FDA officials noted in a news release issued at the time, quoted WebMD. According to the FDA warning, the severe musculoskeletal pain associated with bisphosphonates may occur within days, months, or years after starting treatment. some patients have reported complete relief of symptoms after discontinuing the bisphosphonate; others have reported slow or incomplete resolution.

In the emerging study, the researchers identified 205,466 women at least in their late 60s who began taking an oral bisphosphonate between 2002 and 2008; the group was studied until the spring of 2009, said WebMD. at that time, 716 women required hospitalization for femur fractures. The 716 cases were matched to the nearly 3,600 women who did not suffer a femur fracture, said WebMD.

Women taking the bone drugs for the five-year period or more experienced a 2.7-fold increased likelihood for fractures versus women taking them under 100 days. A secondary review found that women taking the drugs for three years or more experienced a 24 percent risk of osteoporosis-linked breaks than the under-100 day group, added WebMD.

Bisphosphonates are also approved for a variety of other indications, including other bone diseases such as Paget’s disease, and are given to cancer patients for the prevention of fractures due to bone metastases.

Over the past several years, bisphosphonates have been associated with a number of side effects, including Osteonecrosis of the Jaw/Dead Jaw Syndrome, Esophageal Cancer, Fractures, Atrial Fibrillation, and Severe Musculoskeletal Pain. Osteonecrosis of the jaw (ONJ), or dead jaw syndrome is a condition in which the bone tissue in the jaw fails to heal after minor trauma such as a tooth extraction, causing the bone to be exposed. The exposure can eventually lead to infection and fracture and may require long-term antibiotic therapy or surgery to remove the dying bone tissue. In 2005, the FDA ordered that the label for Fosamax and other bisphosphonates be updated to include warnings about ONJ.

TransPharma Medical ltd., a specialty pharmaceutical company focused on the development and commercialization of drug products utilizing a proprietary active transdermal drug delivery technology, announced today successful results of a Phase I clinical trial of its self-applied ViaDerm-Calcitonin product for the treatment of musculoskeletal disorders such as osteoarthritis and musculoskeletal pain.

the Phase I study was an open label single dose cross-over trial to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of ViaDerm-Calcitonin in 12 postmenopausal women treated with 4 different transdermal Calcitonin doses (60-300 mcg) compared to 100IU of Miacalcin, the subcutaneous injected form of the Calcitonin.

Study results demonstrated a clear PK dose response corresponding to the escalating doses of the ViaDerm-Calcitonin patches. furthermore, a single administration of ViaDerm-Calcitonin resulted in a statistically significant reduction of bone resorption and cartilage degradation biomarkers, CTX-I and CTX-II, similar to the reduction obtained with daily injections of 100 IU Miacalcin. all doses of ViaDerm-Calcitonin were safe and well-tolerated and demonstrated a favorable profile with regard to skin safety.

Calcitonin is commercially available in subcutaneous, intramuscular and nasal routes for the treatment of postmenopausal osteoporosis, hypercalcemia, and Paget’s disease. Calcitonin is a very safe drug that has been widely used for many years and is currently being assayed for the treatment of osteoarthritis and various musculoskeletal clinical painful conditions.

“We are very pleased with the results of this study, which demonstrate that our transdermal Calcitonin is safe and as efficacious as a subcutaneous injection,” said Dr. Daphna Heffetz, CEO of TransPharma Medical. “It leads us to believe that enhancing these capabilities with the ease of use, virtual painlessness, small size and portability of our ViaDerm system may open up a myriad of possibilities to expand the therapeutic applications of Calcitonin beyond the current approved indications.”

About the Self Applied ViaDerm Drug Delivery System

TransPharma’s ViaDerm drug delivery system incorporates a handheld electronic device, which creates microscopic passageways through the outer layer of the skin allowing for transdermal delivery of a wide variety of drugs from a patch. the system provides a cost-effective, easy-to-use, virtually pain-free, self-administered solution that enables the safe, reproducible and accurate delivery of a broad range of product candidates, including hydrophilic small molecule such as peptides and proteins.

About Osteoarthritis

Osteoarthritis is a degenerative joint disease involving gradual degradation of joints. Symptoms may include joint pain, tenderness, stiffness, locking of the joint and swelling. When bone surfaces become less well protected by the loss of cartilage, the bone may be damaged, leading to the various Osteoarthritis symptoms, and a decreased quality of life. In severe cases the joint might need replacement surgery. Osteoarthritis is the leading cause of chronic disability, affecting nearly 27 million people and totaling $60 billion annually in related healthcare costs in the U.S. alone.

About Musculoskeletal Pain

Non-malignant musculoskeletal pain is the most common clinical symptom that causes patients to seek medical attention and is the major cause of disability in the world. Musculoskeletal pain can arise from a variety of common conditions including osteoarthritis, rheumatoid arthritis, osteoporosis, surgery, low back pain, and bone fracture. the musculoskeletal market is the sixth largest therapeutic category by sales.

About TransPharma Medical

Established in 2000, TransPharma Medical ltd. is a specialty pharmaceutical company focused on the development and commercialization of drug products utilizing its proprietary active transdermal drug delivery technology. the company aims to develop multiple drug products through strategic partnerships with leading pharmaceutical companies and through independent product development. TransPharma currently has 3 drug products in clinical trials: ViaDerm-hPTH (1-34) product for the treatment of osteoporosis developed in collaboration with Eli Lilly and currently in Phase 2b clinical studies; ViaDerm-GLP1 agonist for the treatment of type II diabetes that has completed phase 1b clinical study; and the ViaDerm-Calcitonin which has completed a Phase 1 clinical trial. For more information, please visit the Company’s website at transpharma-medical.com.

Business Wirebusinesswire.com/

Last updated on: 11/01/2011 10:00:01

-weight loss
-fatigue
-stomach pain
-back pain
-loss of appetite
– she has been in so much pain that all she does is sit in her rocking chair in tears
-i'm very worried along with the rest of my family
-she has gone to the doctors and has an MRI on monday
-she has spotting on her pancreas too.
-also she has osteoporosis in her spine
-any tips on this is GREATLY apreciated.

Osteoporosis means “porous bone””, often no symptoms of bone loss until the bones become so weak that sudden strain, bump or fall causes a fracture.  Osteoporosis is a bone condition distinguished by low bone density and weakening of bone strength.  it can be diagnosed by means of a low radiation scan, which measures bone mineral density.   Most associate osteoporosis to elderly, however, some cases showed as early as 19 years old suffer from osteoporosis.

Heredity is the significant risk factor in acquiring osteoporosis, if a parent has an history of this disease the children has double the risk to occur on them.  another is malnutrition of a fetus, which results in lower bone density in childhood.  also, certain medical conditions, such as Cushing’s disease, diabetes, and hyperthyroidism can contribute to osteoporosis.   The reason why four times more women suffer from osteoporosis than men is due to menopause in women results in reduction of estrogen that protect bone mass.  and, a diet low in calcium and vitamin D is an adding factor to bone failure.  Lastly, lifestyle of limited physical activity, such as smoking, is an additional risk factor of osteoporosis.

Prevention of Osteoporosis is put down in childhood and adolescence foundation.  that is when 90 percent of a person’s total bone mass is reached.  Calcium plays an important role in having a strong skeletal structure, because it is stored  mainly in the bones.  Sources of calcium are milk and dairy products such as yogurt and cheese; canned sardines and salmon (eaten with the bones); almonds; oatmeal; sesame seeds; tofu; and dark green leafy vegetables.  Vitamin D however is required for the calcium to be absorbed by the body.  Vitamin D is produced in the skin through sunlight exposure.  at least ten minutes sunbathing contributes to preventing the development of osteoporosis as it provides around 600 units of Vitamin D.   It can also be found in foods such as egg yolks, saltwater fish and liver.  Exercise is usually not being stressed out as one way prevention.  Exercise during childhood and adolescence helps to increase bone mass, and in old age helps to prevent loss of bone mass.  Exercises in which muscles work against gravity or other forces without overstressing the bones and joints such as weight-bearing and resistance exercises are highly recommended.  Walking, climbing stairs and light dancing are simple but effective weight-bearing exercises.

True changing lifestyle is difficult but what benefits come to those who make the effort to do so is that they may avoid being one of the many millions worldwide who suffer from osteoporosis.