Vol. 7 No. 28
Botox, Botox Cosmetic and Myobloc have been linked to severe adverse events, including respiratory failure and death, after being used for a variety of conditions, the FDA said. As a result, the agency is reviewing clinical trial safety data and postmarketing event reports for Allergan’s Botox and Botox Cosmetic (botulinum toxin type A) and Solstice Neurosciences’ Myobloc (botulinum toxin type B).
The adverse events may be related to overdosing and occurred after both FDA-approved and nonapproved uses. There is no evidence the reactions are related to a product defect, the agency said in an early communication.
The reported adverse reactions are similar to botulism, which occurs when botulinum toxins spread beyond the injection site. The symptoms include difficulty swallowing, weakness and breathing problems. The most severe adverse events occurred in children treated for limb spasticity associated with cerebral palsy, which is not an FDA-approved use. In fact, botulinum toxins have not been established as safe and effective for that condition or for any condition in children younger than 12.
Other serious adverse events occurred after treatment of a variety of conditions using a range of botulinum toxin doses. The effects were reported as early as one day and as late as several weeks following treatment.
The pediatric botulism cases occurred in patients younger than 16 and included such adverse events as dysphagia, respiratory problems and death. No deaths were reported in the adult botulism cases.
The FDA did not tell healthcare professionals to stop prescribing the products but advised that they be on alert for systemic effects after administration of botulinum toxins.
The labeling for botulinum toxin products contain language saying important systemic adverse events, such as difficulty breathing, have occurred in patients with neuromuscular disorders after local injections of the toxins. The FDA has evidence that similar systemic toxicity after use of the products can result in patients with other underlying conditions.
The agency will announce its conclusions and recommendations after completing a review of clinical trial safety data, postmarketing adverse event reports and medical literature.
More information can be found at www.fda.gov/cder/drug/early_comm/botulinium_toxins.htm. — Emily Ethridge
A judge in Florida has ruled that Mylan’s generic levothyroxine sodium product should be removed from the state’s negative formulary, allowing Florida pharmacists to substitute Mylan’s product in place of a brand drug.
Mylan said it will make its product available in Florida pharmacies as soon as motions and other procedural steps are finished. While Florida’s Board of Medicine and Board of Pharmacy voted not to appeal the decision, Abbott Laboratories, which makes Synthroid (levothyroxine sodium), has filed an appeal.
Mylan filed a petition against Florida authorities in August 2007 challenging the inclusion of its product on the negative formulary. Levothyroxine sodium is indicated for treating hypothyroidism and pituitary thyroid-stimulating hormone suppression.
Mylan’s product is therapeutically equivalent to other brand products in addition to Synthroid, including King Pharmaceuticals’ Levoxyl and Forest Laboratories’ Levothroid. The FDA approved Mylan’s product and other generic versions of levothyroxine sodium in 2004 (DID, June 25, 2004).
“This ruling is not just a victory for Mylan, it’s a major victory for the citizens of Florida who have been denied access to lower-cost levothyroxine sodium for years,” Mylan Chief Operating Officer Heather Bresch said.
Last year, the FDA tightened potency standards for levothyroxine sodium products, requiring the products to meet a 95 percent to 105 percent potency specification until expiration instead of a 90 percent to 110 percent range (DID, Oct. 5, 2007). — Breda Lund
The European Commission (EC) is considering allowing drug companies to disseminate some information about their prescription products on television and radio programs.
The EC’s ban on direct-to-consumer advertising of prescription medications would remain in effect. However, companies could disseminate nonpromotional, objective, relevant, evidence-based information to patients about their medications.
Last year, the EC adopted a report that showed member states have varying rules on what information about medical products can be available, resulting in unequal patient access and product information. The proposal aims to reduce differences in access to information among member states.
Under the proposal, each member state would set up a national co-regulatory body to monitor companies’ information activities and adopt a code of conduct for patient information. Companies would have to inform the regulatory bodies about their activities before disseminating the information. The regulatory bodies would act when companies failed to comply with the code. No requirement for the bodies to issue prior approval is included in the proposal.
An EU advisory committee, such as the existing Pharmaceutical Committee, would oversee the national co-regulatory bodies and consult on national codes of conduct.
The companies’ information could not compare medical products or provide information that differs from approved patient information, the proposal says. In addition, healthcare providers should remain the main source of product information. The EC monitoring procedures would distinguish between situations in which the patient is passively receiving information (“push”) or actively searching for information (“pull”).
“Pushed” information includes TV and radio programs with factual information, printed material distributed to patients and written information in printed media. “Pulled” information includes registered internet sites, presentations, seminars and written solicited information.
Prohibited ways of distributing information would include unsolicited emails or phone calls, internet pop-up ads and TV and radio slots not linked to the program content.
The proposal is meeting with some resistance. Consumers International, a federation of consumer groups, called the proposal “the first step toward U.S.-style drug advertising and concepts.”
“Drug companies will say this is about information provision, but patients and consumers need to know this is really about increasing profit margins through advertising,” the group added.
Contributions are due April 7. The proposal can be seen at ec.europa.eu/enterprise/pharmaceuticals/pharmacos/docs/doc2008/2008_02/info_to_patients_consult_200802.pdf. — Emily Ethridge
Allergan’s recently launched overactive bladder treatment Sanctura XR scored some early victories on the managed care front as the company aggressively pursues favorable formulary status for the drug, Indevus Pharmaceuticals, Allergan’s partner for the drug, said.
Indevus receives 12.5 percent of the revenue derived from the sales of both Sanctura (trospium chloride) and its extended-release formulation, Sanctura XR. Allergan gained U.S. marketing rights for the drugs when it acquired Esprit Pharma last year.
“There have been some clear, early, impressive wins on the managed care side,” Indevus CEO Glenn Cooper said during the firm’s Feb. 8 earnings call. “Allergan has an extraordinary managed care capability … aggressive and obtainable targets in terms of lives covered and preferred status, which we think will far exceed the coverage status for [Sanctura].”
Sanctura, the immediate-release formulation of trospium, had sales of $4.5 million during the fourth quarter of 2007, Allergan said. Those sales are dwarfed by Pfizer’s Detrol (tolterodine tartrate) franchise, which earned $219 million during the same period.
When Allergan released its year-end earnings for 2007, it said the Sanctura family of products should have $70 million to $100 million in sales during 2008. More than 30 million Americans are estimated to have an overactive bladder — a market in which Cooper anticipates Sanctura can thrive. Allergan estimates that peak sales of the drugs could reach $400 million.
The products have a superior safety profile, according to Cooper, with the lowest dry mouth rates of any overactive bladder treatment.
Sanctura does not cause adverse central nervous system effects because it is not believed to cross the blood-brain barrier. In addition, no clinically relevant drug interactions are associated with the drug, an important consideration for physicians as the patients with overactive bladders tend to be on multiple medications, Cooper said. — Christopher Hollis
AstraZeneca has asked for summary judgment in the case it filed to protect its ’288 patent for its bipolar disorder drug Seroquel against generic drugmakers Teva Pharmaceuticals and Sandoz.
In a letter filed with the U.S. District Court for the District of New Jersey Feb. 6, Henry Renk, an attorney for AstraZeneca, asked for permission to immediately file a motion for summary judgment that the company’s patent for Seroquel (quetiapine fumarate) is not obvious (i.e., valid) and that there has been no inequitable conduct. According to the letter, these are the only legal matters still at issue in the case.
“The proposed motion will eliminate the need for expert discovery, thereby saving considerable time and expense,” Renk said in the letter to Judge Joel Pisano. “However, if Teva informs AstraZeneca that it intends to launch a 25-mg product, AstraZeneca may seek an expedited litigation schedule.”
The FDA recently decided that, because Seroquel 150-mg tablets have not been withdrawn from the market for safety or effectiveness reasons, the agency can accept and approve applications for generic versions of the drug (DID, Jan. 25). AstraZeneca holds approval for the 150-mg strength but has never marketed the product in the U.S., and the 150-mg strength is listed in the discontinued section of the FDA Orange Book. AstraZeneca does market 25-, 50-, 100-, 200-, 300- and 400-mg Seroquel tablets.
Teva does not comment on matters of pending litigation, spokeswoman Denise Bradley told DID. Sandoz did not return calls seeking comment by press time. — Martin Gidron
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