DID - July 26, 2007 Issue

Vol. 6 No. 146

House Committee Set to Deliberate Bill Affecting ESA Reimbursements

Two House committees will consider reducing Medicare reimbursement rates for erythropoietin-stimulating agents (ESAs) today during its debate on the Children’s Health and Medicare Protection Act of 2007.

The bill, H.R. 3162, includes a section that would establish in 2010 a single-payment system for dialysis centers treating end-stage renal disease (ESRD) covering 96 percent of the estimated costs for the products. The House Ways and Means and Energy and Commerce committees will hold markup sessions on the bill today.

The bill, introduced by House Energy and Commerce Committee Chairman John Dingell (D-Mich.), and Reps. Charles Rangel (D-N.Y.), Pete Stark (D-Calf.) and Frank Pallone (D-N.J.), also reduces reimbursement rates for ESAs administered by large dialysis centers, whether at the facility or at the patient’s home. Under the proposed scheme, reimbursements for 2008 and 2009 would be set at $8.75 for every 1,000 units of Amgen’s Epogen (epoetin alfa) and $2.92 per microgram of Amgen’s Aranesp (darbepoetin alfa), or, if less, 102 percent of the average sales price for the products.

In addition, the bill would have large dialysis centers defined as being owned or managed by a corporate entity that, as of July 24, runs 300 or more centers.

Currently, the CMS reimburses $9.10 per 1,000 units of Epogen and $3.04 per microgram of Aranesp, the agency told DID.

The proposed bill would also establish quality incentive payments for dialysis centers in 2008, 2009 and 2010. The performance standards under the program include maintaining 92 percent of patients with ESRD with average hematocrit levels of 33 percent (11 grams per deciliter). Other factors such as iron management, dialysis adequacy and vascular access are also included in the performance standards, according to the bill.

For 2009 and 2010, target hematocrit levels should conform to FDA-approved physician labeling, according to the bill.

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will hold a joint meeting Sept. 11 with the Drug Safety and Risk Management Advisory Committee to discuss safety issues surrounding ESAs (DID, July 20). The Centers for Medicare & Medicaid Services (CMS) recently updated its ESA monitoring policy for patients with ESRD to reflect recent FDA warnings regarding use of the products (DID, July 23). Previously, the CMS altered its policy for ESA reimbursement to eliminate payments for many cancer indications. The FDA’s Oncologic Drugs Advisory Committee recommended earlier this year that continued marketing of ESAs be contingent on additional studies and warnings on physician labeling.

During a Senate Finance Committee confirmation hearing held yesterday on the nomination of Kerry Weems for CMS administrator, Sen. Mike Crapo (R-Idaho) said the agency’s policies regarding ESAs might be too strict.

The bill, H.R. 3162, can be accessed at energycommerce.house.gov/cmte_mtgs/FC072507MU/CHAMP_003_xml.pdf — Christopher Hollis 


FDA Report Calls for Guidances on Nanotechnology Approval Issues

The FDA’s Nanotechnology Task Force released a report recommending the agency issue guidances to inform industry on how the agency plans to regulate products that use nanotechnology materials, with a focus on safety, the agency announced.

The report also addresses regulatory and scientific issues related to nanotechnology. FDA Commissioner Andrew von Eschenbach, who established the task force last year, endorsed the report’s recommendations July 23 (DID, Aug. 10, 2006).

Von Eschenbach said the report “sets the stage for a comprehensive approach to the regulation of products … including a focus on product safety,” according to FDA Deputy Commissioner for Policy Randall Lutter.

Nearly all products the FDA regulates could use nanoscale materials, which present similar challenges to other emerging technologies, according to the report. However, as size varies within the nanoscale, properties related to the product’s safety and efficacy could change as well, the report said.

Because nanotechnology materials are so small (a nanometer is a billionth of a meter), they can have very different physical properties than their larger counterparts. These differences — such as altered magnetic properties, altered electrical or optical activity, increased structural integrity, and increased chemical and biological activity — give these materials great potential for use in a variety of products.

This “emerging and uncertain nature” of nanotechnology highlights the need for a “transparent, consistent and predictable” regulatory pathway, Lutter said.

Agency guidances should clarify what information manufacturers must give the FDA about products that use nanotechnology, how the agency will make distinctions about nano-size materials in its review process and when using nanotechnology could change a product’s regulatory status, the report says. The report recommends that manufacturers contact the FDA early in the development process to make the agency aware of the nanotechnology use.

The report also says the FDA should evaluate the data it needs to regulate nanotechnology products, develop internal expertise and assess the capacity of its current testing approaches to determine the safety and effectiveness of nanoscale materials. However, products will most likely not need specific labels to indicate they used nanotechnology, according to Lutter.

The agency can implement the task force’s recommendations with current and foreseeable resources, Lutter said. However, he added that the FDA did not have a current budget estimate for the activities and said, “There’s always the opportunity to do more with more.” For example, if the agency had more resources, the industry guidelines would probably be released earlier, he said.

The report’s extensive “to do” list should remind Congress it needs to address the agency’s “chronic underfunding,” former FDA Deputy Commissioner for Policy Michael Taylor said. Last year, Taylor said the agency did not have the legal or financial capacity to regulate new products containing nanomaterials (DID, Oct. 6, 2006).

Some industry groups, however, said that while the FDA did need more resources to regulate nanotechnology products, its authorities and capabilities were sufficient (DID, Oct. 9, 2006).

The task force’s report shows the FDA’s commitment to a transparent and open public process for developing regulatory policies, Taylor added. All draft guidance documents will be made available for public comment before being finalized, the agency said.

The FDA will take steps to begin drafting guidances by product area and developing calls for data in the next few months, according to Lutter. — Emily Ethridge


Grassley, Baucus Question Avandia Advisory Committee

Sens. Chuck Grassley (R-Iowa) and Max Baucus (D-Mont.) sent a letter to FDA Commissioner Andrew von Eschenbach questioning the agency’s upcoming review of Avandia’s safety as well as the alleged treatment of a senior FDA official who raised concerns about the drug.

The letter questions the composition of the FDA advisory committees that will meet July 30 to review GlaxoSmithKline’s Type 2 diabetes drug and other drugs in its class (DID, July 17). The agency recently issued waivers for conflicts of interest to six members of the committees, including Steven Nissen, who conducted a meta-analysis that found Avandia (rosiglitazone maleate) increased the risk of death from cardiovascular causes by 64 percent (DID, May 22).

The lawmakers criticized the FDA for allowing its Office of New Drugs (OND), which approved and defended Avandia, to control the meeting instead of the agency’s Office of Surveillance and Epidemiology (OSE). “Under Commissioner von Eschenbach’s leadership, it seems that drug manufacturers’ interests may be allowed to trump science,” Baucus said.

The lawmakers added they did not “understand the logic” behind the decision to have OND lead the July 30 advisory committee meeting. In addition, Baucus and Grassley found it “troubling” that out of the six FDA staff members who will participate at the advisory committee meeting, four are from the OND.

Von Eschenbach told the lawmakers he was working to give OSE greater responsibility over drug safety, according to the letter. 

In addition, the Senate Finance Committee staff found out that a senior medical official in the OND who was once the primary reviewer for Avandia was told to stop participating in the review of the drug’s potential cardiovascular safety issues, according to the letter.

The officer was removed while the OSE’s Division of Drug Risk Evaluation (DDRE) was recommending a black box warning for congestive heart failure on Avandia’s labeling, the letter said.

Several FDA employees told committee staff that the officer had the most experience with Avandia’s drug class and had been investigating it for approximately six years. The officer’s replacement was someone without experience in the drug class, according to the letter.

Grassley had previously expressed concerns over the FDA’s treatment of former DDRE Deputy Director Rosemary Johann-Liang, the letter added. Johann-Liang was punished for recommending the black box warning on Avandia’s labeling for congestive heart failure, according to the lawmakers.

“It’s time to stop this dangerous and repetitive balance where the FDA tries to shoot the messenger when it doesn’t want to hear the message,” Grassley said.

The lawmakers requested a response to the letter before the July 30 meeting. The letter can be viewed at finance.senate.gov/press/Bpress/2007press/prb072407f.pdf. — Emily Ethridge


Schering Sues Barr Over Temodar ANDA

In the third such announcement this month, Barr Pharmaceuticals reported this week that its subsidiary Barr Laboratories is involved in patent litigation with Schering over its plans to market generic Temodar.

Barr said it believes that it is the first to file an abbreviated new drug application (ANDA) containing a Paragraph IV certification for Temodar (temozolomide) 5-, 20-, 100- and 250-mg capsules.

The company announced last week that it has been sued by Sepracor over its plans to seek approval of generic Xopenex (levalbuterol HCl) (DID, July 18). The previous week, Barr confirmed it is involved in litigation with Boehringer Ingelheim over generic Aggrenox (aspirin/extended-release dipyridamole) (DID, July 16).

While three Paragraph IV patent challenge suits in one month seems like a lot, David Harper, a partner with McDonnell Boehnen Hulbert, said that amount of patent litigation is not beyond reason for a large company like Barr.

In the most recent announcement, Barr said it filed its ANDA for a generic version of the cancer drug in March and, after receiving the FDA’s notice of acceptance, notified the NDA holder, Schering, and the patent owner, Cancer Research Technology (CRT).

Schering and CRT filed suit July 20 in the U.S. District Court for the District of Delaware to prevent Barr from proceeding with the commercialization of its product.

In their complaint, the plaintiffs say Barr’s product would infringe on the patent covering Temodar and request an injunction to prevent Barr from selling a generic version of the drug.

Temodar is indicated for treating glioblastoma multiforme in addition to radiotherapy, as well as for treating refractory anaplastic astrocytoma. The product had U.S. sales of approximately $320 million during the 12-month period that ended in May, Barr said, citing IMS Health data. — Breda Lund


Merck to Acquire Cardiovascular Drug Firm NovaCardia

Merck said it will acquire NovaCardia, a privately held pharmaceutical company that specializes in cardiovascular diseases, for an amount of Merck stock equivalent to $350 million plus the amount of cash on hand at the time of closing, which is expected to be within 45 days. 

NovaCardia’s lead investigational drug, KW-3902, is currently undergoing two pivotal international Phase III clinical trials in patients with acute congestive heart failure. The drug is believed to block adenosine-mediated constriction of blood flow to the kidneys and inhibit reabsorption of salt and water by the kidneys, thereby increasing urine volume and maintaining renal function in patients with congestive heart failure.

NovaCardia recently presented preliminary results from a pilot Phase III trial of KW-3902 that “indicated a strong trend toward efficacy for the 30-mg dose,” Merck said. 

According to the company, patients who took KW-3902 experienced a higher rate of improvement in dyspnea, or shortness of breath, a common symptom of congestive heart failure, compared with the placebo group. The drug also enhanced diuresis and mitigated the deterioration of renal function that patients undergoing standard treatment often suffer from. The data were presented at the European Society of Cardiology’s Heart Failure 2007 Congress. — Martin Gidron


Spanish Court Upholds Lipitor Patent

A Spanish court has upheld Pfizer’s patent covering the calcium salt of atorvastatin, the active ingredient in Lipitor, while also ruling that a second patent is invalid, Pfizer announced.

Ranbaxy Laboratories had initiated the suit, which was decided by the Commercial Court of First Instance Number 4 in Barcelona, Pfizer said. Lipitor (atorvastatin calcium) is sold in Spain under the brand names Zarator and Cardyl.

This was the fourth time a generic company has challenged Pfizer’s calcium salt patent in Spain, Pfizer said. The patent was upheld in one previous case and invalidated in two others. The decisions have been appealed. Pfizer said the calcium salt patent expires in July 2010.

“This is a victory not only for Pfizer, but for all innovators pursuing high-risk medical discoveries and for the patients who benefit from those discoveries,” Pfizer General Counsel Allen Waxman said.

Ranbaxy has challenged Pfizer’s Lipitor patents in several other countries, including Ireland, where a court recently ruled in favor of Pfizer (DID, July 11).

A Norwegian court ruled in May that four of Pfizer’s Lipitor patents in are either invalid or not infringed on by Ranbaxy’s generic product. Pfizer said it planned to appeal (DID, May 30).

In Denmark, a court granted Pfizer a preliminary injunction earlier this year blocking the sale of Ranbaxy’s product pending a final decision (DID, Feb. 26). Previously, a Canadian court invalidated one Lipitor patent but upheld another (DID, Jan. 29). — Breda Lun

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