DID - Feb. 5, 2008 Issue

Vol. 7 No. 24

President’s Request Would Give FDA $2.4 Billion in Fiscal 2009

The Bush administration is proposing a 5.7 percent increase in the FDA’s budget for fiscal 2009 to improve drug safety, allow user fees to fund a direct-to-consumer (DTC) advertisement review program and fund the creation of an approval pathway for follow-on biologics. The request would bring the agency’s total budget to $2.4 billion, including $1.77 billion in direct budget authorities and $628 million in user fees.

Most of the user fees would come from prescription drug user fees recently reauthorized under the FDA Amendments Act (FDAAA), the agency said. The request includes $35 million for drug safety activities already included in FDAAA, $10 million more than in fiscal 2008. 

The proposed budget raises again the issue of collecting user fees to fund the agency’s voluntary DTC advertisement review program. The program was created under FDAAA last year, but the FDA could not start it because Congress did not allocate the user fees in the agency’s appropriations bill (DID, Jan. 16). Instead, Congress directly appropriated approximately $6.25 million for the review program for fiscal 2008.

By proposing user fees again, the administration is urging Congress to debate the issue anew, FDA Budget Formulation and Presentation Deputy Director Robert Miller said. 

The funding increases in the budget would help modernize drug safety, speed generic drug approvals and provide cost-of-living increases to FDA employees. The FDA said it will expand its work force with 526 additional full-time equivalent staff members in fiscal 2009.

Members of Congress have been calling for increased FDA funding. The House Energy and Commerce Committee recently held a hearing on a report from the FDA Science Board’s Subcommittee on Science and Technology that says insufficient resources are preventing the agency from fulfilling its mission (DID, Jan. 30).

The report found that a lack of funding, inadequate work force, weak scientific base and obsolete IT system prevent the FDA from protecting the public health (DID, Dec. 3, 2007).

Miller said IT funding would be increased to approximately $240 million in fiscal 2009, up from approximately $200 million in fiscal 2007.

In addition, the request proposes a pathway for approving follow-on biologics that would be funded through user fees, President Bush said. The FDA could not give more details on the proposal at press time, but Chief Operating Officer John Dyer said the agency would work with Congress to create legislation allowing a follow-on biologics approval pathway. Several lawmakers recently added follow-on biologics legislation to a new healthcare initiative, giving the issue added momentum in Congress this year (DID, Jan. 31). 

The request also targets $1.2 million to improve the agency’s capability of monitoring counterfeit drugs coming into the country, Miller said. — Emily Ethridge


FDA Considering Centocor’s Psoriasis Drug

Centocor’s biologics license application (BLA) for ustekinumab, a treatment for adults with chronic moderate to severe plaque psoriasis, has been accepted for review by the FDA. 

The ustekinumab BLA includes results from two multicenter, randomized, double-blind, placebo-controlled Phase III trials involving a total of approximately 2,000 patients. One-year findings from the two trials were presented Feb. 2.

In Phase II studies, 81 percent of patients receiving four weekly 90-mg doses of the drug achieved at least 75 percent improvement in their psoriasis at week 12, as measured by the Psoriasis Area and Severity Index, compared with 2 percent of patients receiving placebo, according to Centocor’s parent, Johnson & Johnson (J&J).

Centocor has the U.S. marketing rights for ustekinumab, while Janssen-Cilag, also a J&J subsidiary, has marketing rights in the rest of the world. Janssen-Cilag submitted its marketing authorization application for ustekinumab to the European Medicines Agency last December.

If approved, ustekinumab would join Abbott Laboratories’ Humira (adalimumab) as new players in the moderate to severe chronic plaque psoriasis market. The European Union approved Humira for this indication last December, and the FDA followed suit in January (DID, Jan. 22). — Elizabeth Jones


FDA Approves Inhaled Asmanex for Children

The FDA has given the green light to Schering-Plough’s Asmanex Twisthaler for once-daily dosing in children as young as 4.

The company said this makes Asmanex (mometasone furoate inhalation powder) the first and only inhaled corticosteroid approved as a preventive therapy for the maintenance treatment of moderate and mild persistent asthma in patients age 4–11.

The dose approved for these pediatric patients is 110 micrograms (one puff) administered in the evening. This is half the dosage level approved for patients age 12 and up. The 220-microgram dose received FDA approval March 31, 2005.

The FDA’s approval of pediatric Asmanex is based in part on the results of a 12-week placebo-controlled trial of 296 patients age 4–11 who had been diagnosed with asthma for at least six months. These patients showed significant improvement in percent-predicted forced expiratory volume in one second compared with those taking a placebo. Secondary endpoints of morning and evening peak expiratory flow and rescue medication use also were positive, Schering-Plough said.

According to updated guidelines from the National Asthma Education and Prevention Program cited by Schering-Plough, inhaled corticosteroids are the preferred foundation therapy for initiating long-term control in children with persistent asthma. — Martin Gidron


MHRA Recommends Against Generic Prescribing for Biologics

Biologics should be prescribed using the product’s brand name, rather than the substance name, to prevent pharmacists from automatically substituting a brand biologic with a biosimilar product, according to the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).

Several biosimilar biologic products have been approved by regulators in Europe and the UK. They include Sandoz’s Omnitrope (somatropin), which is similar to Pfizer’s growth hormone product Genotropin, and Binocrit (epoetin alpha), which is similar to Janssen Pharmaceutica’s erythropoiesis-stimulating agent Eprex.

While prescribing drugs by substance name has been seen as a way to increase generic usage and cut costs, the MHRA said in its February issue of Drug Safety Update that “it is good practice to use the brand name” when prescribing biologics. The agency’s reasoning is that, unlike generic versions of chemical drugs, biosimilar products are not considered identical to their reference biologics.

Using the same logic, the MHRA also recommended that physicians reporting adverse drug reactions use the products’ commercial names rather than the substance names to ensure that adverse reactions are reported for the correct reference or biosimilar product.

According to a recent report from the UK Parliament’s Public Accounts Committee, the proportion of prescriptions written using the substance name — so-called generic prescribing — was 83 percent in September 2006. The report, announced last month, contained recommendations for ways the UK’s health system can increase generic usage and save more than 200 million pounds a year. — Breda Lund


Amgen to License Drug Candidates, Sell Subsidiary to Takeda

Takeda Pharmaceutical has signed a deal under which it will acquire Japanese development and commercialization rights for as many as 13 molecules from Amgen’s pipeline. The candidates treat a range of indications, including oncology, inflammation and pain.

Takeda will become Amgen’s worldwide partner for oncology candidate motesanib diphosphate and pay Amgen $100 million upfront and $175 million in milestones. The company also will acquire all shares of Amgen’s Japanese subsidiary, Amgen KK, a transaction anticipated to close in the first quarter of the year.

Amgen will retain certain co-promotion rights for all candidates, it said.

The sales come as Amgen faces several legal and safety-related problems. The New Jersey attorney general issued a subpoena to the company following allegations that it violated patient confidentiality laws and engaged in off-label promotion for Enbrel (etanercept), which is used to treat rheumatoid arthritis, psoriatic arthritis and moderate to severe psoriasis, as a treatment for mild psoriasis (DID, Jan. 21).

The company also has to meet again with the FDA’s Oncologic Drugs Advisory Committee to discuss safety issues surrounding erythropoeisis-stimulating agents Aranesp (darbepoetin alfa) and Epogen (epoetin alfa). During a previous meeting, the committee recommended additional studies and further safety restrictions for the products (DID, Jan. 28). —  Elizabeth Jones

Amgen Rejects Roche Royalty Offer for Mircera

Roche is pushing forward in its effort to bring its renal anemia treatment Mircera to the U.S. market, making its case in a proposal to the federal district court in Boston.

The move is part of the company’s ongoing patent litigation with Amgen, which is defending its patents on Epogen (epoetin alfa) and Aranesp (darbepoetin alfa) against Roche’s Mircera (methoxy polyethylene glycol-epoetin beta). All three drugs are erythropoeisis-stimulating agents (ESAs), the safety of which has been called into question recently.

The patent trial is now in its “remedy phase,” and the judge asked Roche to submit a proposal outlining the economic terms under which the court might allow Roche to market the drug in the U.S. Roche proposed to pay Amgen a royalty of 20 percent, Linda Dyson, director of public affairs for Roche, told DID. However, Amgen has rejected this as insufficient.

“In October, a jury held four of Amgen’s patents on erythropoietin valid and infringed by Roche’s peg-EPO product,” Dan Whelan, director of nephrology corporate communications for Amgen, told DID. “As Amgen demonstrated at the injunction hearing, Roche’s product and marketing proposals confer no clinical benefit, serve no public interest and would actually increase the cost of treatment to Medicare, especially in the short term. Roche’s royalty proposal is inadequate to compensate Amgen for Roche’s infringement and lacks any merit. We believe an injunction is the appropriate remedy.”

Dyson disagreed. “We believe it is important for there to be competition and choice for U.S. patients and providers in the management of renal anemia,” she told DID. “Amgen has had an extended monopoly for the last 20 years, blocking new therapeutic options from being introduced to patients in this country.”

In November 2007, the FDA approved Mircera for the treatment of anemia associated with chronic kidney failure (DID, Nov. 16, 2007).

However, the launch for the product has been delayed pending the outcome of the patent litigation with Amgen. A federal district court jury ruled in October 2007 that Mircera infringes on several of Amgen’s patents covering Epogen and Aranesp (DID, Oct. 25, 2007).

The FDA’s Oncologic Drugs Advisory Committee is scheduled to discuss the safety of ESAs in a March 13 meeting (DID, Jan. 28). — Martin Gidron

EC Approves Roche’s Xeloda for Colorectal Cancer

The European Commission (EC) has approved Roche’s chemotherapy drug Xeloda for treatment of metastatic colorectal cancer.

Xeloda (capecitabine) is approved for use with any chemotherapy in all lines of treatment, with or without the company’s Avastin (bevacizumab). It potentially can replace the previous standard intravenous chemotherapy in all colorectal cancer regimens, according to Jim Cassidy, chair of medical oncology at the University of Glasgow, Scotland. Cassidy was the lead investigator for one of the Xeloda trials presented to the European Medicines Agency.

Roche said the drug allows patients to have fewer clinic visits than standard intravenous chemotherapy, reducing hospital treatment time by 160 hours.

Last month, the company’s Avastin also received a label extension in Europe for the treatment of metastatic colorectal cancer. The broader label allows Avastin to be used in combination with any chemotherapy, including Xeloda, for first and later treatment lines in metastatic colorectal cancer patients.

More than 400,000 people in Europe are diagnosed with metastatic colorectal cancer every year. — April Astor

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

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