DID - Oct. 4, 2007 Issue

Vol. 6 No. 195

FDA Holding Public Meeting on ‘Behind-the-Counter’ Drugs

The FDA is holding a public meeting on whether it should make certain prescription drugs available behind the counter (BTC), which would not require customers to have a prescription but would require “intervention by a pharmacist.”

The purpose of the meeting, which will be held Nov. 14 in Washington, D.C., is to solicit opinions on such matters as the impact of the proposed BTC category on patient access to safe and effective drug products, as well as the effect on drug prices and patient compliance with drug therapy.

Some groups argue that pharmacists could talk to patients to ensure safe and effective use of a BTC drug that otherwise might require a prescription. These groups also argue that classifying certain drugs as BTC could increase patient access to medications that may be underutilized, particularly by patients without health insurance. BTC status is already used in other countries, including Australia, Canada, France, New Zealand, the UK, Denmark, Germany, Italy, the Netherlands, Sweden and Switzerland.

Before switching a drug from prescription to BTC, most of these countries examine which of the drug’s indications are suitable for self-medication, including self-diagnosis, with the help of a pharmacist, as well as the drug’s potential for side effects or overdose and whether pharmacists can help minimize those risks.

Comments may be submitted to www.accessdata.fda.gov/scripts/oc/dockets/commentdocket.cfm. — Martin Gidron


FDA Opens Flu Vaccine Comment and Info Docket

The FDA has opened a docket for information and comments from vaccine manufacturers and other interested parties on the development of safety and effectiveness assessments for pandemic influenza vaccines according to an announcement to be published in the Oct. 4 Federal Register.

The agency said it needs help developing programs for adverse events surveillance following the administration of pandemic influenza vaccines, as well as protocols to study the effectiveness of influenza vaccines in pre-pandemic and pandemic situations.

In its May 31 guidance for flu vaccine manufacturers, the FDA said all vaccine sponsors should expect the agency to seek their involvement in plans to collect additional safety and effectiveness data, such as through epidemiological studies, when the vaccine is used (DID, June 1).

In the docket, the FDA is requesting information on the design of potential studies to assess the effectiveness of influenza vaccine in a pandemic situation, including comments on the potential usefulness of randomized trials, case control studies and additional study designs, as well as potential endpoints.

In addition, the FDA is seeking comments on organizations and entities, such as managed care organizations or other public or private entities that may be able to partner with manufacturers and sponsors to assess safety and effectiveness. The FDA will use these comments to help the agency develop additional guidance documents on postmarketing safety surveillance and effectiveness studies for pandemic influenza vaccines.

Comments and information may be submitted within the next 60 days to www.fda.gov/dockets/ecomments. — Martin Gidron


FDA Says Erbitux Can Be Used Against Advanced Colorectal Cancer

ImClone Systems and Bristol-Myers Squibb (BMS) said the FDA has approved their oncology drug Erbitux for use against advanced colorectal cancer.

The change is reflected in an FDA-approved updated label for Erbitux (cetuximab) that includes overall survival data on the drug’s use as a single agent to treat epidermal growth factor inhibitor (EGFR)-expressing metastatic colorectal cancer (mCRC) patients who have failed to respond to both irinotecan- and oxaliplatin-based regimens.

The FDA’s approval of the companies’ supplemental biologics license application is based on prolonged overall survival from a large, randomized, multi-site Phase III trial comparing Erbitux plus best supportive care (BSC) versus BSC alone in 572 EGFR-expressing mCRC patients who had failed to respond to irinotecan- and oxaliplatin-based regimens.

BSC was defined as all approved palliative therapies designed to alleviate pain and treat other effects caused by mCRC in these patients.

BMS and ImClone are actively exploring the potential of Erbitux to treat other types of tumors, Martin Birkhofer, vice president of Oncology Global Medical Affairs at BMS, said.

Last month ImClone agreed to pay Repligen and the Massachusetts Institute of Technology $65 million to settle a patent lawsuit over Erbitux (DID, Sept. 12). — Martin Gidron


Lilly Cited for Misleading Cymbalta Promotional Materials

Eli Lilly overstated Cymbalta’s efficacy by using pooled clinical trial data in promotional materials sent to physicians, according to an FDA untitled letter sent Sept. 21.

The materials promoted Cymbalta (duloxetine HCl) for the management of diabetic neuropathic pain, an approved indication.

The pooled data, collected from clinical studies submitted in the product’s new drug application, said patients with diabetic peripheral neuropathic pain had significantly less pain interference with overall functioning. The brief pain inventory (BPI) interference subscale was used as the measure for that claim.

When the studies are evaluated individually, they do not show a statistically significant effect on the BPI pain interference subscale when compared with placebo. But when the studies are combined, the data show a statistically significant effect, the FDA said.

“This post-hoc analysis is not a credible source of data,” the FDA told Lilly in the letter, posted on the agency’s website earlier this week.

The FDA also objected to using the BPI subscale to support the claim.

The subscale asks patients to rate their level of pain interference for the following seven functions: general activity, mood, walking ability, normal walk, relationships with others, sleep and enjoyment of life, the agency said.

“Each of the seven items in the BPI pain interference subscale measures a general concept that cannot be adequately captured with a single-item question,” the FDA said. “We do not know of any evidence that patient responses to such questions yield valid data.”

In response, Eli Lilly told DID the BPI scale is a validated and reliable measure of pain and its impact on functioning.

In addition to the agency’s concerns about overstating the drug’s efficacy, the promotional piece omitted some of Cymbalta’s most serious risks.

The professional mailer did not include a contraindication for use of the drug in patients with uncontrolled narrow-angle glaucoma. A warning and contraindication for use of the drug in combination with monoamine oxidase inhibitors, a class of antidepressants, were also omitted.

The agency requested that Eli Lilly immediately cease disseminating the professional mailer and said there were five other Cymbalta promotional pieces with similar claims. The mailer was produced in 2005 and is no longer in use, the company said.

Eli Lilly told DID that it has responded to the untitled letter and looks forward to meeting with the agency to clarify its concerns. The letter can be accessed at www.fda.gov/cder/warn/2007/Cymbalta_wl.pdf. — Christopher Hollis


DeLauro Considering Changes to FDA’s Structure

Rep. Rosa DeLauro (D-Conn.) is looking for new ways to reform the FDA and may introduce legislation to impose a moratorium on direct-to-consumer (DTC) advertisements and split the agency in two.

DeLauro said she would have liked to have seen stronger provisions in H.R. 3580, the FDA Amendments Act that reauthorized the Prescription Drug User Fee Act and gave the FDA more postmarketing authority. While the bill improved the transparency of postmarketing safety information, it did not include giving the FDA mandatory recall authority.

Congress must be vigilant in monitoring the FDA to ensure it implements the new rules and authorities in H.R. 3580. She added, “If it’s not working, we have to move to turn it around.”

H.R. 3580 was recently signed into law, but Congress must continue to “explore additional opportunities to reform” the FDA, she said during a talk at the George Washington University School of Public Health and Health Services.

DeLauro, chairwoman of the House Subcommittee on Agriculture, Rural Development, FDA and Related Agencies, told DID she planned to hold a subcommittee hearing soon on drug and medical device safety.

DeLauro is considering creating legislation that would divide the FDA into two agencies, one focused on food and the other on drugs and medical devices. Each agency would have a commissioner who reports to the HHS secretary, she said.

She is also looking at legislation to institute a three-and-a-half year moratorium on DTC advertisements for drugs and medical devices following their approval, she added.

DeLauro addressed the FDA’s funding, saying, “right now, the Office of Management and Budget sees FDA as just one small part of HHS’ budget.” The House passed a bill in August that would provide $1.69 billion for the FDA for fiscal 2008 (DID, Aug. 6). However, the president has threatened to veto the bill because of its high spending levels and a provision allowing drug importation.

The Senate has not passed a bill to fund the FDA. President Bush recently signed a bill into law that will continue government funding through Nov. 16, giving Congress more time to work on the fiscal 2008 federal budget (DID, Oct. 2).

While DeLauro wants to continue increasing the FDA’s funding, she said she wanted to monitor how the agency was spending it. “I want to see systems in place that show where the money is going,” she said. “You show me the plan; I will work my hardest to get you every dime you need.” — Emily Ethridge


Waxman Questions Marketing of OTC Cold and Cough Products for Children

Rep. Henry Waxman (D-Calif.) asked OTC drug manufacturers why they are marketing cold and cough medications for use in infants after the Consumers Healthcare Products Association (CHPA) recommended the drugs not be used in children younger than 2.

The FDA’s Nonprescription Drugs and Pediatric advisory committees will hold a joint meeting Oct. 18-19 to address concerns of the use of OTC cold and cough medications in children and infants. Several experts submitted a citizen petition describing the lack of evidence demonstrating the products’ safety and efficacy in children and noting injuries in children due to accidental overdose.

This evidence, along with CHPA’s recommendations, “strongly suggest that a number of currently marketed products be removed from the market immediately, and that the marketing of other products be substantially modified,” Waxman wrote in a letter to CHPA President Linda Suydam.

CHPA recommends that the products’ labels change to state that the drugs should not be used in children younger than two. However, several CHPA member companies, including McNeil Consumer Healthcare and Novartis, are marketing the products for use in children younger than 2, Waxman said. The products are labeled for infants and have drawings of babies on the boxes, he added.

The products’ dosage forms and strengths also suggest they are intended for infants, Waxman said. Some of the products for infants are more concentrated than the same product for children because infants require a smaller volume of liquid. The risk of overdose from these highly concentrated dosages is greater than with children’s formulations, Waxman said.

Waxman asked CHPA to explain why it has not asked its member companies to stop marketing products specifically for infants and children younger than 2 and describe the actions the group will take to ensure its members’ products are not marketed for infants and young children. He added that the CHPA-recommended label change would not be enough if the packaging contains other indicators that the product is for infants, such as drawings of babies on the boxes.

CHPA should convey its information on the lack of evidence supporting the use of OTC cough and cold products in children to the American public, as well as ensure its member companies follow the group’s recommendations, Waxman said.

Waxman requested a response by Oct. 12. His letter can be seen at oversight.house.gov/documents/20071003135846.pdf. — Emily Ethridge

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Reporters: Martin Gidron, Emily Ethridge, April Astor, Breda Lund, Christopher Hollis

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