|May 2013, Volume XXIII, No. 3|
By Deepen Joshi
Regulatory & Legislative Highlights
The FDA has sent letters warning seven pharmacy operations that the claims they make about the safety and effectiveness of their compounded "bio-identical hormone replacement therapy" or "BHRT" products are unsupported by medical evidence and are considered false and misleading by the agency, thus violating federal law. Compounded drugs are not reviewed by the FDA for safety and effectiveness. The agency encourages patients to use FDA-approved drugs whenever possible and is concerned that unfounded claims like these mislead both patients and health care professionals.
The pharmacy operations targeted improperly claim that their drugs, which contain hormones such as estrogen, progesterone and estriol (which is not a component of an FDA-approved drug and has not been proven safe and effective for any use), are superior to FDA-approved menopausal hormone therapy drugs and prevent or treat serious diseases, including Alzheimer's, stroke, and various forms of cancer. The pharmacy operations receiving warning letters use the terms "bio-identical hormone replacement therapy" and "BHRT" to imply that their drugs are natural or identical to the hormones made by the body.
FDA's action does not target pharmacists who practice traditional pharmacy compounding and who do not make false or misleading claims about compounded products. All patients who use compounded hormone therapy drugs should discuss menopausal hormone therapy options with their health care provider to determine if compounded drugs are the best option for their specific medical needs. (Source: FDA Website, 29 January 2008)
The FDA approved the Endeavor Zotarolimus-Eluting Coronary Stent, manufactured by Medtronic of Minneapolis, for use in treating patients with narrowed coronary arteries, the blood vessels supplying the heart.
Like all drug-coated stents, the new device is a tiny metal mesh tube coated with a drug. In this case the drug is a new compound called zotarolimus, developed specifically for use on a stent. The stent is crimped around a balloon and delivered to the narrowed section of the coronary artery via a long thin catheter during a procedure known as an angioplasty. Once the stent is positioned, the balloon is inflated, expanding into the vessel wall where it will remain in place, acting as a mechanical scaffold to keep the artery open. Slow release of zotarolimus over time prevents the artery from re-narrowing when new tissue begins to form. This process, known as restenosis, can eventually require a repeat angioplasty.
The Endeavor drug-eluting stent is the first to hit the US market since safety concerns plagued the market two years ago. Use of drug-coated stents compared with their bare-metal predecessors declined after evidence emerged that the drug coatings may increase dangerous clots. Endeavor is one of a new generation of stents the industry hopes can recapture US demand for the drug-eluting devices, sales of which sank to $2 billion last year, down from a peak of $3.1 billion in 2005. (Source: FDA Website, 1 February 2008 and Associated Press, The Boston Globe, 2 February, 2008)
The FDA has licensed a treatment for hemophilia A, a rare, hereditary blood-clotting disorder that affects approximately 15,000 individuals, almost exclusively males, in the United States. The new treatment, called Xyntha Antihemophilic Factor (Recombinant) Plasma/Albumin Free, is licensed for the control and prevention of bleeding, which can occur spontaneously or after an accident or injury in patients diagnosed with hemophilia A and to help prevent surgical bleeding in this patient population.
Manufactured by Wyeth Pharmaceuticals, Xyntha is a genetically-engineered version of factor VIII, a protein essential for the clotting of blood. Factor VIII, known as an anti-hemophilic factor, is missing or decreased in patients with hemophilia A. To make Xyntha, genes from Chinese Hamster Ovary cells (CHO) are modified to produce factor VIII. These CHO cells are free from known infectious agents, and Xyntha undergoes an additional process of viral inactivation. Also, the culture in which the cells are grown is free of any human or animal material. (Source: FDA Website, 21 February 2008)
House Speaker Salvatore DiMasi unveiled a plan that would give $1 billion over 10 years to Massachusetts' life-sciences industry. While DiMasi's proposal differs in some key respects from the one Governor Patrick proposed last year, it does incorporate the major elements of the governor's initiative, designating $500 million in bonds for capital projects, $250 million in research grants and $250 million in targeted tax credits to Massachusetts-based companies.
However, DiMasi is also seeking to put his own imprint on the life sciences plan with an array of narrowly targeted, regional spending initiatives that would benefit individual companies, communities, and University of Massachusetts campuses. These include $12.6 million to build an interchange on Interstate 93 near Andover, where the state wants to spur development of science-related companies; $12.9 million to improve sewage treatment in Framingham, which would benefit an expansion planned by Genzyme; and $30 million for vocational and technical high schools to improve life sciences courses. The bill also calls for $95 million to build a life science center at the University of Massachusetts at Amherst; $90 million for a center for genetic research and genetic therapy on the UMass Medical School campus in Worcester and establishes five regional offices throughout the state that would help businesses decide whether to locate in Massachusetts. (Source: Matt Viser, The Boston Globe, 15 February 2008)
When House lawmakers unveiled the latest version of the state's $1 billion life-sciences bill, a new wrinkle caught some Patrick administration and industry officials by surprise. A provision in the bill would restrict some benefits to companies with a corporate or US headquarters in Massachusetts - apparently shutting out some of the state's largest life-sciences employers, including drug makers Wyeth and Novartis AG. But after reading the bill closely, some observers say the impact could be muted. It turns out the restriction doesn't apply to the $250 million in tax benefits set aside to encourage companies to expand in Massachusetts over the next decade, but only to a narrower set of benefits.
Specifically, the restriction in the House bill applies to $45 million in "bridge loans" and assistance from the Massachusetts Life Sciences Center in setting up clinical trials. It also gives preference to companies with a local headquarters for research partnerships with state universities, job training programs, and access to pre-permitted industrial land - but doesn't preclude non-local companies from receiving those benefits as well. (Source: Todd Wallack, The Boston Globe, 21 February 2008)
The state will spend $4 million to help UMass Lowell build an "innovation center" to assist entrepreneurs in developing, testing, and commercializing medical devices. The center will bring together the engineering expertise of UMass Lowell and the medical know-how of the UMass Medical School in Worcester, with about 40 faculty members from the two schools contributing to the goal of turning ideas for medical devices into products. With construction already underway, the center could be open within a year, according to Stephen McCarthy, a UMass Lowell plastics engineering professor and codirector of the center.
To succeed, medical device start-ups must get through a period known as the "valley of death" in which the product is under development, but not far enough along to attract venture capital. The center aims to help young, promising companies survive that period by giving them access to needed equipment and expertise.
Massachusetts has one of the nation's biggest medical-device industries, led by Boston Scientific, the Natick maker of stents, defibrillators, and other devices that employs more than 28,000 people worldwide. The Merrimack Valley, which includes Lowell, has a particularly large medical device cluster, including firms such as Philips Medical Systems and Straumann AG in Andover, and Zoll Medical of Chelmsford. (Source: Robert Gavin, The Boston Globe, 13 February 2008)
BU administrators overseeing the Biosafety Level-4 lab, the centerpiece of a larger federally sponsored project, had predicted that the facility would be operating by the fall. In a clear setback for BU, which first began pursuing federal grants to build the lab on its South End medical campus five years ago, the NIH has said in a court filing that it now anticipates an ongoing environmental review of the lab will take longer than expected and won't be completed until "on or before April 30, 2009."
The revised NIH schedule also appears to acknowledge blistering criticism of the agency's conclusion that the lab posed no danger to the surrounding neighborhood. In November, an independent panel of scientists concluded that the federal review "was not sound and credible" and failed to adequately address the consequences of highly lethal germs escaping from the lab.
In a federal lawsuit, US District Judge Patti Saris had refused to immediately block construction of the project. But Saris said she would retain oversight of the Biosafety Level-4 lab, leaving open the possibility that she could prevent research with the deadliest germs, including Ebola, plague, and Marburg virus. Once the environmental review is completed, representatives of BU, NIH, and the lab's opponents must appear before Saris again, adding still further time to the lab's opening date. (Source: Stephen Smith, The Boston Globe, 1 February 2008)
Synta Pharmaceuticals of Lexington and its British partner, GlaxoSmithKline PLC, said the FDA has granted orphan drug status to their experimental drug, elesclomol, for metastatic melanoma, a skin cancer. Such status is designed to encourage companies to develop drugs for rare diseases by letting them have seven years of market exclusivity for the products they develop. In November 2006, elesclomol received "fast track" designation from the FDA; the companies can submit clinical data to the FDA as it becomes available rather than wait to submit it all at once for review. (The Boston Globe, 29 January 2008)
Baxter International temporarily suspended production of the widely used blood-thinner heparin because of about 350 possible allergic reactions, including four deaths, primarily in patients undergoing kidney dialysis and heart surgery. Because heparin, a generic drug available for decades, is widely used in hospitals and dialysis centers, Baxter said it isn't suspending sales of the heparin already produced. Officials of the FDA made that decision along with executives of Baxter to avoid shortages.
Baxter supplies about 50 percent of the heparin used in the US, so the possibility of a shortage arising is a real one. Although the company first said it had concluded the reactions were confined to nine lots of heparin, it later said the adverse reactions have spread beyond those lots and to a wider range of dosages. Baxter began recalling the original nine lots January 17th. The FDA decided not to extend the recall beyond those lots.
Leaving a possibly tainted product on the market required an agonizing balancing act by the FDA, and will mean more balancing by kidney specialists, heart doctors and others who use the product. The agency advised doctors to use small amounts of the drug infused over a longer period of time whenever possible. (Source: Thomas M. Burton and Jon Kamp, The Wall Street Journal, 12 February 2008)
Health and Human Services Secretary Mike Leavitt said the Bush administration supports legislation giving the FDA explicit authority over unsafe food or drugs made overseas with the intent of shipping them to the US.
The FDA has been hobbled in its enforcement of imports even as the number of products entering the U.S. has skyrocketed. Recently, some have questioned how the FDA failed to inspect a Chinese plant that supplies much of the active ingredient for Baxter's blood thinner, heparin, which has been linked to hundreds of bad reactions and four deaths.
The letter marked the first time HHS, the FDA's parent agency, supported the effort to give the agency such authority. Earlier, the administrations cabinet-level import-safety panel, which Mr. Leavitt heads, had proposed increasing penalties and other enforcement power over imports and importers, and the Justice Department has supported the amendment for a number of years. (Soure: Jane Zhang, The Wall Street Journal, 23 February 2008)
Controversies about cholesterol drug Vytorin and diabetes drug Avandia are reigniting debate over what evidence the FDA requires to approve drugs - and may generate pressure on the agency to raise its bar. The FDA's system for approving drugs has been criticized as scrutiny grows about Vytorin, co-marketed by Schering-Plough and Merck, in the wake of a study that raised questions about whether the widely advertised blockbuster drug worked better than a cheaper generic.
A shift by the FDA toward tougher scrutiny of new drugs could add hundreds of millions of dollars to the cost of developing a drug at a time when some big drug makers are struggling to replenish product pipelines. In addition, any pre-approval holdup eats into the manufacturer's crucial time to sell the drug before protective patents expire and generic competition leaps in.
The lawmakers' interest is the latest sign that the flap over Vytorin, in addition to a recent controversy about the safety of GlaxoSmithKline PLC's Avandia, is adding new fuel to a long-running debate over FDA approval standards - and, specifically, a mechanism known as "surrogate markers." Vytorin and Avandia went on the market based largely on evidence that they helped control patients' cholesterol and blood sugar, respectively. Sometimes a drug works on a surrogate marker but doesn't deliver the promised benefit for the primary health problem. Or a drug can have side effects that don't surface during initial surrogate marker studies but end up outweighing its benefit. (Source: Anna Wilde Mathews and Ron Winslow, The Wall Street Journal, 25 January 2008)
The FDA granted Abbott Laboratories approval for Simcor, a drug that raises "good" cholesterol and lowers both "bad" cholesterol and triglycerides. Simcor is a combination of two existing, approved treatments: simvastatin, a statin, and Abbott's Niaspan, an extended-release version of niacin, a B vitamin. Statin treatments lower LDL, or bad cholesterol; but they don't treat HDL - good cholesterol - or triglycerides, two other types of lipids associated with cardiac problems if found at abnormal levels.
Simcor's approval is the first for a cholesterol drug since questions cropped up about the effectiveness of another treatment, Merck and Schering-Plough's Vytorin, and could augur well for FDA approval of Merck's Cordaptive cholesterol-lowering drug, which is also based on niacin. The question with Simcor is whether the treatment will be any better at preventing heart attacks or death than the components of the medication alone, the same question that Merck and Schering-Plough face with Vytorin. The two components of Simcor have separately demonstrated an ability to reduce heart attacks and death. It also remains to be seen how many patients will actually make the switch to a combination treatment. (Source: Shirley S. Wang, The Wall Street Journal, 16 February 2008)
The FDA granted accelerated market approval for Genentech's Avastin, a drug to treat advanced breast cancer, in a cliffhanger decision that split the breast-cancer community. Avastin is a biotech drug made from cells that are genetically engineered to replicate the body's own weapons - in this case, an antibody that blocks proliferation of blood vessels that feed tumors. The agency's decision means Genentech can market and sell the drug to oncologists for their breast-cancer patients, pending two other studies.
European Union regulators approved Avastin for breast cancer a year ago. American doctors and activists had been split over whether Avastin's benefit - an extra 5½ months of "progression-free survival" - offers patients tangible benefits or a better quality of life when balanced against severe drug side effects. The FDA's decision fuels ongoing debate over the agency's approval standards for cancer drugs. Traditionally, the "gold standard" has been to show that a drug is able to help patients live longer, rather than simply arrest tumor growth. (Source: Marilyn Chase and Anna Wilde Mathews, The Wall Street Journal, 23 February 2008)
The FDA can't keep up with requirements to inspect domestic makers of medical devices to assure manufacturing quality, and the agency rarely examines foreign facilities, according to congressional investigators. In testimony scheduled to be delivered before a House Energy and Commerce subcommittee, the Government Accountability Office will tell lawmakers that it found "weaknesses" in the agency's oversight of an industry that makes products ranging from contact lenses to defibrillators. According to FDA officials' own estimates, overseas makers of the riskiest products, such as pacemakers, were examined only every six years, and moderate-risk device manufacturers on average went an estimated 27 years between FDA inspections.The GAO testimony on medical devices will be a part of the hearing's broader effort to highlight an issue that has turned up in reports and critiques over the past few years: concerns that the FDA's resources and technology aren't enough to meet its regulatory responsibilities to oversee drugs, food and other products. The medical device testimony will say that FDA officials estimated US makers of the highest-risk products are examined, on average, every three years. Domestic manufacturers of moderate-risk devices get inspected every five years. Both are supposed to be looked at every two years. (Source: Anna Wilde Mathews, The Wall Street Journal, 29 January 2008)
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