|
By popular request, NAMS provides ongoing information regarding news about therapeutic options in menopause management. Note, however, that this mention does not imply endorsement. Marketers of menopause therapies for North America are encouraged to forward to NAMS (info@menopause.org) all press releases regarding new products and dosages.
—On October 15, Pfizer’s acquisition of Wyeth closed, after which Wyeth ceased to be an independent company.
—The October 5 issue of “The Pink Sheet” reported that Abbott Laboratories has plans to acquire the prescription drug business of Solvay Pharmaceuticals, a marketer of Prometrium (progesterone capsules) in the US.
—An October 1 press release from Bayer HealthCare Pharmaceuticals, Inc. announced that the FDA approved a new indication for Mirena (levonorgestrel-releasing intrauterine system) for the treatment of heavy menstrual bleeding in women who choose to use IUD contraception. Mirena is the first and only contraceptive approved in the US for this indication.
—A September 11 press release from Quest Diagnostics announced that the FDA approved the OVA1 Test, the first blood biomarker test to determine likelihood of ovarian cancer in women with a pelvic mass. The new test was developed by Vermillion, Inc., a molecular diagnostics company, in cooperation with Quest, which has exclusive rights to offer the test to the clinical reference laboratory market in the US for 3 years.
—On August 29, Hisamitsu Pharmaceutical Co., Inc. (a Japan-based global pharmaceutical company that is the world’s largest manufacturer of trandermal patches) acquired Noven Pharmaceuticals, which will continue as a standalone business unit operating at its current locations in Miami and New York City, according to a press release from Noven. Novogyne Pharmaceuticals remains a joint venture between Noven and Novartis Pharmaceuticals. Novogyne markets Vivelle Dot (transdermal estradiol).
—The August 31 issue of “The Pink Sheet” reported that Warner Chilcott purchased Proctor & Gamble’s entire pharmaceutical business on August 24, with the deal expected to close around November 1. The article indicates that this $3.1 billion acquisition significantly bolsters the Irish drug maker’s sales force and adds to its already lucrative women’s health portfolio (eg, Femhrt, Estrace Cream, Loestrin 24 Fe) with the addition of Actonel (risedronate), among others, while freeing P&G to focus on its personal, oral, and feminine care consumer health products (eg, Prilosec OTC, Crest, Oral-B). Warner Chilcott also gains P&G’s research pipeline and co-promotion rights to Enablex (darifenacin) for the treatment of overactive bladder.
—Eli Lilly and Company announced on August 18 that initial results from its pivotal, 5-year, Phase III GJAD “GENERATIONS” trial for arzoxifene met its primary endpoints of significantly reducing the risk of vertebral fracture and invasive breast cancer in postmenopausal women. However, the study failed to demonstrate a statistically significant difference in key secondary endpoints, such as nonvertebral fractures, cardiovascular events, and cognitive function, compared to placebo. In addition, certain adverse events (eg, venous thromboembolic events, hot flashes) were reported more frequently in the active treatment group. The company has decided not to submit the compound for FDA review and clinical trials will be discontinued. The final study results will be published in 2010.
—The International Society for Clinical Densitometry (ISCD) has announced that a proposed new federal bill would again take direct aim at osteoporosis testing, reducing reimbursement for DXA. These additional cuts come at a time when ISCD and other organizations are trying to reverse cuts that have already been implemented during the past 3 years. Those in the US who wish to join the lobbying initiative are encouraged to contact ISCD (at dfiorentino@iscd.org).
—A June 11 press release from the FDA announces that Cumberland Pharmaceuticals’ Caldolor, the first injectable dosage form of the common pain medication ibuprofen, has been approved to treat pain and fever. Available for hospital use only, Caldolor should be administered in 400-800–mg doses, over 30 minutes, every 6 hours for acute pain. In a clinical trial of 319 women who had undergone an elective abdominal hysterectomy, patients were less likely to request morphine for pain on an as-needed basis when administered Caldolor.
—Novartis Pharmaceuticals reports that the FDA has approved a new indication for Reclast (zoledronic acid) Injection. The drug is now indicated for prevention of postmenopausal osteoporosis. The recommended regimen is a
5 mg–infusion given once every 2 years intravenously over no less than 15 minutes. With this additional indication, Reclast is approved for use in early to advanced bone loss.
—On May 7, 2009, the FDA announced that it is requiring manufacturers of two prescription topical testosterone gel products (Androgel 1% and Testim 1%) to include a boxed warning instructing users to wash their hands after using the product and to cover the treatment skin with clothing. This action was required after the agency received reports
of adverse effects in children who were inadvertently exposed to testosterone through contact with another person
being treated with these products (ie, secondary exposure). Although these products are for use only in men, NAMS recommends that similar precautions be taken when prescribing custom-compounded topical testosterone therapies
for women at menopause and beyond.
—On March 13, Solvay Pharmaceuticals announced its decision to discontinue supplying Estratest and Estratest H.S. (esterified estrogens and methyltestosterone) Tablets in the United States. The company “recognizes the product serves as an important therapeutic alternative in the treatment of menopausal symptoms and continues to stand behind its safety and efficacy” but states that “the decision was made based upon a variety of business factors.” Effective March 31, 2009, the company will no longer accept orders for new product from its wholesale customers. Healthcare providers may continue to prescribe the product as long as pharmacies have an adequate supply to fill the prescription.
—The February 2 issue of “The Pink Sheet” featured an article regarding Amgen’s denosumab (“d-mab,” for short), a fully human monoclonal antibody. An application was filed with the FDA on December 19, 2008, for the prevention and treatment of postmenopausal osteoporosis as well as prevention and treatment of bone loss in patients undergoing hormone ablation for either prostate or breast cancer. The drug is administered through twice-yearly subcutaneous injections.
—The January 26 issue of “The Pink Sheet” reports that the FDA approval of Pfizer/Ligand’s osteoporosis drug Fablyn (lasofoxifene) has been delayed due to a concern regarding an apparent increase in mortality among Fablyn users. Pfizer proposed a 50,000-patient post-marketing safety cohort study to help resolve the issue.
—On January 12, 2008, the FDA issued a statement that drug company representatives can distribute, but not discuss, reprints of journal articles on off-label uses for drugs.
—On December 4, 2008, Medical Marketing and Media Online announced that Azur Pharma has entered into an agreement with BioSante Pharmaceuticals to acquire US rights to Elestrin, a gel formulation of estradiol indicated for the treatment of moderate to severe vasomotor symptoms.
—On November 13, Wyeth issued a press release announcing that the FDA had approved Premarin (conjugated estrogens) Vaginal Cream 0.5 g for a new indication—treatment of moderate to severe postmenopausal dyspareunia—and a new less frequent, twice-weekly dosing regimen to treat the condition (in addition to the previously approved dosing regimen of 21 days on, 7 days off). The release indicated that more than 1 in 4 untreated postmenopausal women experience dyspareunia, a symptom of vulvar and vaginal atrophy.
—On November 13, the FDA announced that a review of clinical trial data has revealed no clear association between overall bisphosphonate exposure and the rate of serious or nonserious atrial fibrillation (AF). In addition, increasing the dose or duration of therapy was not linked to an increased risk of AF. This FDA review, which began in October 2007, was prompted by publications in May 2007 that described increased rates of serious AF in two studies with alendronate or zoledronic acid therapy. According to an alert issued by Medwatch, the FDA’s safety information and adverse event reporting program, healthcare professionals should therefore not alter their prescribing patterns for bisphosphonates and patients should not stop taking their medication.
—On September 4, 2008, a broad range of US medical professional and health groups (including NAMS, American College of Obstetricians and Gynecologists, The Endocrine Society, American Society for Reproductive Medicine, National Association of Nurse Practitioners in Women’s Health, and Society for Women’s Health Research, among others) sent an official communication to members of Congress to reiterate their collective support for the FDA’s recent actions against a small group of compounding pharmacies manufacturing BHRT drugs (for more, see stories below). This communication said that “We are united in our opposition to H. Con. Res. 342/S. Con. Res. 88, which states that ‘the FDA should reverse its policy that aims to eliminate patients’ access to compounded medications containing estriol that their physicians prescribe for them.’ We urge you not to become a cosponsor of this resolution.”
—The International Academy of Compounding Pharmacists designated September 10, 2008, as BHRT National Congressional Call-in-Day, urging concerned constituents to call their elected members of Congress and urge them to influence the FDA to reverse its policy on “bioidentical hormone replacement therapy” (BHRT), specifically estriol. The new policy states that pharmacies may not compound drugs containing estriol without investigational new drug authorization. (See January 2008 story below for more.) Their Web site states that FDA’s recent action is “not based on scientific data or any medical justification.”
—The July 19-20, 2008, issue of The Wall Street Journal reported that the Israeli company Teva Pharmaceutical Industries Ltd., the world’s largest generic drug company, will acquire rival Barr Pharmaceuticals of Woodcliff Lake, NJ. A division of Barr, Duramed Pharmaceuticals, markets many brand name and generic products in the menopause and contraceptive fields, including Enjuvia, Cenestin, and Seasonale.
—On June 23, 2008, the FDA approved a label change for Reclast (zoledronic acid) Injection to include the results from the HORIZON Recurrent Fracture Trial. The indication has been expanded to include use to reduce the incidence of new clinical fractures in patients at high risk of fracture, defined as a recent low-trauma hip fracture.
—The FDA has approved a 150-mg once-monthly dose of Actonel (risedronate sodium) tablets for the treatment and prevention of postmenopausal osteoporosis. This dose compares to the 5-mg daily dose regimen.
—According to the May 26 issue of “The Pink Sheet,” the so-called “sunshine bill” is gaining momentum. Senate legislation may set up a federal reporting program for drug and device companies to disclose their gifts to physicians. Even as Congress debates the subject of transparency for transactions between drug companies and drug prescribers, more firms (eg, Amgen, AstraZeneca, Lilly, Pfizer) have begun their own move toward disclosure. Stay tuned to this controversial discussion.
—On March 3, The Wall Street Journal reported that Wyeth had received approval for Pristiq, the third antidepressant on the US market in a class known as serotonin-norepinephrine reuptake inhibitors (SNRIs), following Wyeth’s Effexor XR and Lilly’s Cymbalta. Wyeth is still seeking a separate indication for menopausal symptoms; that approval is delayed pending an additional year-long study. According to the report, the agency’s safety concerns aren’t a factor for Pristiq’s antidepressant use because the effective dose is much lower than for menopause symptoms.
—On January 9, the FDA announced that warning letters had been sent to seven pharmacy operations, indicating that the claims they make about the safety and effectiveness of their so-called
“bioidentical hormone replacement therapy” are unsupported by medical evidence and are considered
false and misleading by the agency. Pharmacies may not compound drugs containing estriol without investigational new drug authorization. There is no scientific basis for using saliva testing to adjust hormone
levels. Read the full press release, letters, and the FDA’s advice about compounding at www.fda.gov/cder/pharmcomp/default.htm. According to the January 14 issue of “The Pink Sheet,” the FDA’s authority to oversee compounding has been under legal assault for several years. But while compounders are working against regulation in court—saying it should be left up to individual states—other groups, including the American Medical Association and the Government Accountability Office, have been urging the FDA to increase its oversight. The article states that letters sent on January 9 mark the first time the FDA has warned compounding pharmacies about these products, although 34 warning letters were sent in 2005 by the FDA, in conjunction with the Federal Trade Commission, to Web site operators making similarly misleading promotional claims for “natural” OTC progesterone cream. A Congressional Research Service survey of state laws is underway to help determine whether oversight of compounding should be located at the federal or state level.
—On January 7, an FDA Alert highlighted the possibility of severe musculoskeletal pain in patients using bisphosphonates (marketed as Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa). Although this adverse side effect is included in the prescribing information for all bisphosphonates, the FDA is concerned that the association between these therapeutic agents and severe musculoskeletal pain “may be overlooked by healthcare professionals, thereby delaying diagnosis, prolonging pain and/or impairment, and necessitating the use of analgesics.” The side effect may occur within days, months, or years after starting therapy. Some patients have reported complete relief of symptoms after discontinuation, whereas others have reported slow or incomplete resolution. Risk factors associated with this side effect are unknown. Severe musculoskeletal pain is in contrast to the acute phase response characterized by fever, chills, bone pain, myalgias, and arthralgias that sometimes accompanies initial administration of IV bisphosphonates and may occur with initial exposure to once-weekly or once-monthly doses of oral bisphosphonates. The FDA states that “healthcare professionals should consider whether bisphosphonate use might be responsible for severe musculoskeletal pain in patients who present with these symptoms and consider temporary or permanent discontinuation of the drug.
—An article in the January 8 issue of The Wall Street Journal reported that the FDA approved just 19 novel drugs during 2007, the lowest number since 1983. The article states that industry argues that the slowdown is the result of a tougher FDA, but the FDA says that its standards haven’t changed. Hypotheses for what may be driving the slowdown are presented: big pharma’s research labs are too bloated, bureaucratic, and risk averse; industry has shifted its focus away from novel drugs and toward tweaking existing medicines to maximize sales during the research drought; or maybe the easy drugs have been found and fresh scientific breakthroughs are needed before drug researchers can get traction again.”
—McNeil Personal Products Company has launched K-Y Brand Liquibeads, an OTC estrogen-free vaginal moisturizer that is delivered via vaginally inserted beads that “dissolve within minutes, then release to provide benefits for up to 4 days.”
—Bayer HealthCare announced that its Consumer Care Division has acquired from Mission Pharmacal Company its global Citracal line of OTC calcium supplements.
—Allergan, Inc. completed its acquisition of Esprit Pharma, Inc., marketer of Estrasorb (estradiol topical emulsion) for vasomotor symptoms associated with menopause and Sanctura XR (trospium chloride) for the treatment of overactive bladder.
—A press release dated November 19 announced that Schering-Plough Corporation had completed its acquisition of Organon BioSciences N.V., marketers of NuvaRing (etonogestrel/ethinyl estadiol) contraceptive ring and other brands.
—The October 8 issue of The Wall Street Journal reported that the European Union (EU) regulators have approved the Novartis bone drug, zolendronic acid, for postmenopausal osteoporosis. Marketed in the EU as Aclasta, the drug was recently approved for this indication in the United States as the brand name Reclast. (See September 2007 story below.)
—Duramed Pharmaceuticals, Inc., announced on October 2 that its synthetic conjugated estrogens, B (Enjuvia) is now indicated for treatment of moderate-to-severe vaginal dryness and pain with intercourse, symptoms of vulvar and vaginal atrophy associated with menopause. This is the first and only oral estrogen FDA approved for the treatment of these specific symptoms. Enjuvia is already approved for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. In addition to launching the new indication, the
0.9 mg tablet strength, approved by the FDA in April, will now be added to the existing range of tablet dosing strengths.
—On September 14, the FDA approved Lilly’s raloxifene (Evista oral tablets) for a new use—reducing the risk of invasive breast cancer in two populations: (1) postmenopausal women with osteoporosis and (2) postmenopausal women at high risk for invasive breast cancer. Its decision was based on data from multiple trials, including STAR, RUTH, and MORE. In the STAR trial, for example, the observed incidence rates of invasive breast cancer per 1,000 women per year were 4.4 for raloxifene and 4.3 for tamoxifen, the first SERM approved for reducing the risk of invasive breast cancer. Raloxifene labeling states that the drug is not indicated for the treatment of existing breast cancer, reduction of the risk of recurrent breast cancer, or reduction of risk of noninvasive breast cancer. Raloxifene, a selective estrogen-receptor modulator (SERM), is already approved for the prevention and treatment of postmenopausal osteoporosis. Labeling contains a black-box warning of increased risk of venous thromboembolism and death from stroke.
—According to “The Pink Sheet,” Novartis received FDA approval of the osteoporosis treatment claim for zoledronic acid (Reclast Injection) on August 17. Labeling states that Reclast reduces the incidence of hip, vertebral, and nonvertebral osteoporosis-related fractures. The Swiss firm will seek an indication for prevention of clinical fractures after hip fracture. Reclast is the first once-yearly treatment for postmenopausal osteoporosis. A yearly 5 mg/100 mL IV infusion takes about 15 minutes. In April, Reclast was approved for treatment of Paget’s disease of the bone at the same dose. The single dose is reported to have a wholesale acquisition cost of $1,041. Zoledronic acid is also marketed by Novartis as Zometa (4 mg injection) for treatment of hypercalcemia of malignancy and multiple myeloma and bone metastases of solid tumors. Reclast is not yet available in Canada.
—The FDA has approved a new dosing option for using risedronate (Actonel), indicated for the prevention and treatment of osteoporosis. A 75 mg tablet is taken on two consecutive days each month rather than a 5 mg tablet taken daily. BMD increases are similar to those in women treated with the lower dose of daily Actonel at both 6 and 12 months. Actonel is marketed by The Alliance for Better Bone Health, a collaboration between Procter & Gamble Pharmaceuticals and sanofi-aventis.
—The FDA has ruled that the term “selective estrogen-receptor modulator” (SERM) can no longer be used, and should be replaced with “estrogen agonist-antagonist.” No acronym has yet been suggested.
—In July, VIVUS, Inc. received FDA approval for Evamist, the first estradiol transdermal spray. It’s indicated for treatment of moderate to severe vasomotor symptoms. KV Pharmaceutical Company will market the product within its subsidiary, Ther-Rx Corporation. US launch is expected in early November.
—Zestra Laboratories announced on July 10 the results of its yet unpublished multi-site RCT of 296 women using its OTC nonhormonal Zestra Feminine Arousal Fluid for improving sexual experiences. The trial’s results, according to the marketer, show that the product is well tolerated and provides desire, arousal, and sexual satisfaction benefits. Zestra commented that the FDA does not require clinical trials for this type of product.
—According to “The Pink Sheet,” Wyeth received an “approvable” letter from the FDA on July 23 for a new nonhormonal treatment, desvenlafaxine (Pristiq), indicated for vasomotor symptoms. The FDA has requested an additional clinical trial that is at least a year in duration.
—“The Pink Sheet” also reported on July 30 that the FDA’s Oncologic Drugs Advisory Committee has voted to recommend approval of Lilly’s osteoporosis drug, raloxifene (Evista), for reducing invasive breast cancer risk in postmenopausal women with osteoporosis and postmenopausal women at high risk of breast cancer. This nonbinding recommendation awaits the FDA’s final ruling.
—Lil’ Drug Store Products, Inc., the marketers of Replens Long-Lasting Feminine Moisturizer, has announced the US launch of a new and novel vaginal lubricant: Intimate Options Personal Lubricant Mousse.
The company states that it has all the benefits of a vaginal lubricant without the typical unpleasant effects. The company’s recent market research study among 1,500 women revealed that the top five self-reported negative aspects of lubricants were: messiness (65.7%), messes up the bed (49.0%), drippy/doesn’t stay in place (43.3%), feels cold at initial application (41%), and interrupts the moment (25.7%). The company states that the new mousse product is light when dispensed, becoming smooth and silky on contact, and it does not run or become sticky. It is available in a 2-oz Unscented Personal Lubricant Mousse, a 2-oz Vanilla Personal Lubricant Mousse, and a 5.64-oz 2-in-1 Massage and Personal Lubricant Mousse with a hint of Vanilla Cinnamon.
—The FDA has approved OTC sale of the weight-loss prescription drug orlistat (Xenical, marketed
by Roche) as alli (GlaxoSmithKline) to be used in combination with a reduced-calorie, low-fat diet. The OTC product is available in half the strength of the Rx drug, in a starter pack of 90 60-mg capsules. Orlistat
prevents absorption of dietary fat (30% with 120 mg Xenical and 25% with 60 mg alli). A 16-wk controlled trial
(Anderson et al. Ann Pharmacother 2006) of 60 mg TID with meals in overweight (not obese) patients
(avg BMI 26.8) on a reduced-calorie, low-fat diet found that patients taking the drug lost 1.15 kg more than
those taking placebo. Orlistat causes flatulence with oily spotting, loose stools, and fecal urgency in 20%-40%
of patients on a low-fat diet. Side effects would presumably increase with higher doses or higher fat intake.
The drug also interferes with absorption of fat-soluble vitamins and possibly other drugs, and may increase the anticoagulant effect of warfarin.
—Upsher-Smith Laboratories, Inc., announced FDA approval for Divigel (estradiol gel), 0.1%, for the treatment of moderate to severe hot flashes associated with menopause. The company states that this new product offers the lowest approved dose of estradiol available for the treatment of these symptoms. It is estimated that the product will be commercially available in the United States in July.
—Novo Nordisk has announced the US launch of Activella 0.5 mg/0.1 mg (estradiol/norethindrone acetate) tablets, a new lower dose hormone therapy option for the treatment of moderate to severe menopause symptoms and prevention of postmenopausal osteoporosis. The company states that this is the lowest estradiol and norethindrone acetate combination commercially available in the United States.
Marketers of menopause therapies for North America are encouraged to forward to NAMS (info@menopause.org) all press releases regarding new products and dosages. |