DID - Nov. 4, 2009 Issue

Vol. 8 No. 215

First MAPP Outlines CDER Coordinating Committee Responsibilities

CDER’s Medical Policy Coordinating Committee (MPCC), which includes scientists and policy staff, has received its first Manual of Policies and Procedures (MAPP) outlining committee duties that include helping develop guidance documents and overseeing implementation.

The MPCC designates subcommittees and working groups to develop the policies, guidances or other procedures that the full MPCC considers, according to the MAPP posted on CDER’s website this week.

The MPCC also is expected to be a forum for scientific, technical and regulatory issues suggested by sources such as participants at CDER regulatory briefings, and the committee coordinates workshops on medical policy as needed, according to the MAPP that took effect Nov. 2. The MPCC subcommittees and working groups will usually be comprised of four to six members each.

CDER’s associate director for medical policy and the director of the Office of New Drugs (OND) serve as co-chairs of the MPCC. Other permanent members include a director from each Office of Drug Evaluation within OND; the associate director for planning and informatics; and the directors of the offices of biostatistics, compliance, surveillance and epidemiology, translational sciences and clinical pharmacology.

The MAPP delineates the responsibilities of key MPCC members such as the co-chairs and executive secretary. The subcommittees and working groups are expected to develop and draft policies and procedures at the request of the committee, track milestones and provide updates on projects, among other duties, according to the MAPP.

The MAPP can be accessed at www.fdanews.com/ext/files/UCM188694.pdf. — Martin Berman-Gorvine


FDA May Consider New Guidance in Transparency Initiative

The agency plans to release a report early next year on regulatory communication that might lead to new regulations, laws or a guidance that would describe the circumstances in which the FDA should disclose safety and efficacy information in pending and withdrawn NDAs, an FDA official says.

The report’s recommendations would be posted for public comment before further action is taken, Joshua Sharfstein, FDA principal deputy commissioner and leader of the FDA Transparency Task Force, said at the group’s second public meeting Tuesday.

Last June, the FDA said it had formed the task force to develop recommendations for improving the transparency of its operations and decisionmaking process (DID, June 3). The task force includes the agency’s center directors, associate commissioner for regulatory affairs, chief scientist and chief counsel.

Two of the initiatives planned are the regulatory communication report and a project the agency plans to begin before year’s end — FDA 101, a section of the agency’s website for consumers that will be devoted to frequent questions and commonly misunderstood aspects of FDA procedures.

The third phase of the initiative involves FDA transparency with regulated industry. “We’ve heard from industry they don’t understand sometimes how the FDA is approaching a particular field or type of application,” Sharfstein said. “Over time we want to provide some recommendations on that topic … and they’ll be available for public comment.”

At the meeting, experts addressed what information, if any, the FDA should disclose about pending applications, particularly in cases in which companies publish study results the agency considers to be too optimistic.

Nirmal Mulye, president of Nostrum Pharmaceuticals, said the FDA should disclose information on safety and efficacy, while K&L Gates Partner Michael Hinckle, representing the Generic Pharmaceutical Association, contended that pending ANDAs are confidential.

James Miller, visiting scholar at the Johns Hopkins Bloomberg School of Public Health, pointed out that if the FDA begins responding to information made public by sponsors during the application process, sponsors would disclose as little data as possible.

If trial data are not publicly available, and a company receives a deficiency letter from the agency, Hinckle advised that “the place to resolve that is with the back-and-forth with the FDA.”

“If you put it out in the public domain it becomes very difficult for the applicant to change the agency opinion,” he said.

Experts also advised the FDA’s task force on disclosing information in withdrawn or abandoned applications that may have had safety or efficacy concerns. This information is “exactly the kind of information that should be made public,” Diana Zuckerman, president of the National Research Center for Women & Families, said, citing issues with Cox-2 inhibitors such as Vioxx (rofecoxib). “The sooner you know about a problem with one drug, the sooner you can look for the problem in similar drugs,” she said.
Ekopimo Ibia, director of global medical and regulatory policy for Merck, agreed it would probably be best to disclose the information, as long as the disclosure process involves the sponsor. “I think the onus is on the FDA to look into how best to disclose that information and protect the public if indeed the withdrawal was the result of a significant safety issue,” he added.

But Zuckerman said the reasons for NDA withdrawal should be disclosed routinely. Making a determination every time would be a burden for the FDA.

Although some panelists suggested revealing the information on a case-by-case basis to companies with similar drugs, or applications for similar drugs, Zuckerman argued that the standards for disclosure must be consistent.

“If the decision not to tell the public is made on the basis of this being proprietary information, then it shouldn’t be disclosed to anybody,” Zuckerman said. “Either it’s proprietary information or it isn’t.” — April Hollis


Supreme Court Asks for Justice’s View in Pfizer Clinical Trial Case

The U.S. Supreme Court has invited the Justice Department’s Office of the Solicitor General to file a brief in a case in which Nigerian plaintiffs are suing Pfizer over deaths and other adverse events in children during its 1996 clinical trial of the antibiotic Trovan.

Pfizer appealed to the Supreme Court July 8 for a writ of certiorari after the U.S. Court of Appeals for the Second Circuit decided in January that the drugmaker could be sued in the U.S. The pediatric clinical trial of the company’s antibiotic Trovan (trovafloxacin mesylate) is the source of the litigation (DID, Feb. 3).

Two hundred children with bacterial meningitis, a life-threatening brain infection, were enrolled in the Phase III open-label, randomized study that tested the effectiveness of Trovan compared with Roche’s antibiotic Rocephin (ceftriaxone sodium) (DID, Jan. 11, 2008). Trovan was administered to 99 children, and 101 others received Rocephin.

In response to Pfizer’s Supreme Court appeal, the plaintiffs’ attorneys filed a brief with the Supreme Court in August alleging that “despite knowing that Trovan had the potential to cause serious side effects in children, [Pfizer] nonetheless rushed at the opportunity to test children struck ill by a sudden bacterial meningitis epidemic in northern Nigeria in 1996.”

The brief further alleges that Pfizer’s actions represent “a gross violation of international legal norms prohibiting nonconsensual medical experimentation.”

Attorneys for both sides did not respond to requests for comment by press time. The case is Pfizer Inc. v. Rabi Abdullahi, et al, Supreme Court docket number 09-34.

Separately, Pfizer agreed in July to pay as much as $30 million to finance healthcare initiatives, and more to support study participants to settle a lawsuit filed by the Kano State government in Nigeria (DID, July 31). — Martin Berman-Gorvine


J&J Plans to Cut as Many as 8,000 Jobs Internationally

Johnson & Johnson (J&J) is planning to eliminate as many as 7,000 to 8,000 jobs worldwide by 2011, as part of a reorganization plan focused on bringing new products to market.

The positions to be reduced represent about 6 percent to 7 percent of the company’s workforce, spokeswoman Carol Goodrich told DID Tuesday.

The move is expected to save the company $1.4 billion to $1.7 billion when fully implemented in 2011, with $800 million to $900 million of that savings occurring next year, J&J says in a statement. The savings will be derived primarily from reducing levels of management, increasing individual spans of control, and simplifying business structures and processes, the company says. J&J intends to use the savings to support product introductions and other growth.
The company expects to record an associated pretax restructuring charge of $1.1 billion to $1.3 billion in the fourth quarter. Earlier this year, the company discussed expected FDA action on several J&J pipeline drugs as the company tried to offset the loss of some of its blockbuster drug sales to generic competitors, including migraine treatment Topamax (topiramate) (DID, April 15).

Separately Tuesday, Eli Lilly disclosed that it will eliminate as many as 191 employees by Dec. 31 related to an Indianapolis plant closing, the company says in an Oct. 30 letter to the Indiana Department of Workforce Development.

Lilly notes it is restructuring its osteoporosis, diabetes and neuroscience sales forces. Its letter is available at www.in.gov/dwd/files/Eli_Lilly_10_30_09.pdf. — April Hollis


Supreme Court Refusal to Hear Apotex Appeal Protects Plavix Patent

The Supreme Court denial of Apotex’s petition challenging a patent on Sanofi Aventis and Bristol-Myers Squibb’s (BMS) blood-thinner drug Plavix protects a patent on the drug that Apotex had contended was not strong enough to maintain exclusivity.

The court’s decision not to review the case ends an eight-year legal battle over the blockbuster drug that began when Apotex applied for FDA approval to market a generic Plavix (clopidogrel bisulfate) in November 2001. Plavix sales reached $9.3 billion in 2008, according to the companies’ SEC filings.

The product’s original patent expired in 2003, and Apotex claimed that a second patent on the drug — the ‘265 patent that expires in November 2011 — is invalid because it covers only a minor advance that is not substantial enough to protect the drug’s exclusivity, according to the company’s petition to the Supreme Court.

“Sanofi’s investment, in other words, was protected by — and rewarded with — the earlier patents,” Apotex says. “To reward Sanofi for its earlier investment by upholding a later patent on an inexorable minor advance is to violate the patent [process].”

Sanofi and BMS responded to Apotex’s filing for FDA approval by filing suit against the company in 2002 and won a 30-month stay on the approval of the ANDA that eventually expired. Apotex began marketing a generic version of Plavix in August 2006, but Sanofi won a preliminary injunction blocking sales of the product a few weeks later.

Appeals by Apotex were subsequently denied by the U.S. District Court for the Southern District of New York and a federal appeals court, leading up to the Supreme Court’s decision Monday.

The court’s decision could be costly for Apotex because under the law, if a firm launches a generic before the outcome of the patent challenge and loses, it can be liable for three times what the brand drug patent holder lost in sales while the generic product was on the market.

Under the terms of a failed Plavix settlement agreement that are still in effect, however, Sanofi and BMS agreed to limit Apotex’s liability to no more than 50 percent of Apotex’s net sales of generic Plavix. If BMS and Sanofi launch an authorized generic, that figure is limited to 40 percent (DID, Aug. 22, 2006).

Despite the loss by Apotex, the outcome probably will not deter other generic-drug makers from launching products while litigation is still pending, Kurt Karst, an associate with Hyman, Phelps & McNamara, told DID.

“I don’t think that you can equate that with making a broad statement about at-risk launches,” Karst said. “It’s really case-by-case, depending on what a particular company thinks a strength of a patent is.”
The Supreme’s Court’s move follows a decision by the Canadian Supreme Court last year to dismiss an appeal by Apotex challenging a patent on Plavix (DID, Nov. 10, 2008).

Apotex did not respond by press time to a request for comment.

The case, Apotex v. Sanofi-Synthelabo, docket No. 09-117, can be found at origin.www.supremecourtus.gov/docket/09-117.htm. — David Belian

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Reporters: Martin Berman-Gorvine, David Belian, April Hollis

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