Drug Industry Daily - Nov. 18, 2010 Issue

Vol. 9 No. 225

First Pharma Exec to Be Excluded by OIG Resigns

The former CEO and chairman of the board of KV Pharmaceutical has become the first pharmaceutical company executive to be excluded from participation in federal healthcare programs under a new HHS Office of Inspector General (OIG) guidance.

Marc Hermelin, the son of KV’s founder, was recently notified by the OIG that he would be excluded effective Thursday, according to the company.

Hermelin, who is the largest single KV shareholder, voluntarily resigned from his position as chairman effective Nov. 10, the company added.

As part of a recent settlement agreement between the OIG, Hermelin, his wife and KV, Hermelin will divest his shares over an undisclosed period of time. According to the agreement, Hermelin also relinquishes all of his voting powers.

Compliance with the agreement means the OIG will not exercise its authority to exclude KV from federal healthcare programs, which can account for about half of a drug company’s U.S. business.

The company added that in a separate divestiture agreement with the OIG, it agreed to dissolve its generic subsidiary, Ethex Corporation, which was the source of several recalls and manufacturing issues in 2008. Ethex was cited for distributing oversized painkiller tablets as well as manufacturing interruptions and inefficiencies, according to the Department of Justice.

Following Hermelin’s resignation and the OIG agreements, KV’s press release said the company has resolved its remaining issues with the OIG and is positioned to continue to participate in federal healthcare programs now and in the future.

The OIG’s exclusion of Hermelin follows the organization’s Oct. 20 guidance, which states that it will begin holding company executives responsible for criminal activities conducted by pharmaceutical companies (DID, Oct. 29).

Hermelin has had a troubled history with KV. In 2008, he was fired with cause “for FDA regulatory and other compliance matters and management misconduct,” according to an SEC filing dated Dec. 5 of that year (DID, Dec. 30, 2008).

In May 2007, KV was told, along with 20 other companies, to stop marketing unapproved drug products containing guaifenesin before Nov. 2007. But KV continued to market and distribute the drugs, leading the FDA and U.S. Marshals to seize $24.2 million worth of unapproved drugs from the company (DID, July 31, 2008).

KV signed a consent decree with the FDA last year following recalls and holds of all of its products. In September, KV received the FDA’s approval to begin shipping its first products since the hold.

With Hermelin officially no longer part of the company’s decision-making process, KV is taking steps to improve its business ventures. In a separate announcement Wednesday, the company pronounced Greg Divis its permanent CEO. Divis has served as the interim CEO since June 10; he also serves as president of Ther-Rx Corporation, KV’s branded pharmaceutical subsidiary.

The company also decided to focus its future on developing and commercializing branded specialty pharmaceuticals. KV is working with the FDA to gain approval to begin shipping two of its key products, Clindesse (clindamycin phosphate) and Gynazole (butoconazole). KV hopes to add a drug to prevent premature birth, Gestiva (17-alpha hydroxyprogesterone), to that list if it gains FDA approval during this fiscal year.

These goals will be supported by KV’s recently secured debt financing package, worth up to $120 million. — Molly Cohen


Medicare Panel Supports Prostate Cancer Drug Provenge

Advisors to Medicare have voiced support for Dendreon’s prostate cancer drug Provenge as the Centers for Medicare & Medicaid Services (CMS) decides whether to adopt a national policy covering the immunotherapy.

The Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) voted Wednesday that Provenge (sipuleucel-T) improves survival in asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. Voting was done via a confidence scale, with the mean of voting members expressing intermediate confidence in the survival benefit.

The panel also voted that the drug significantly improves the avoidance of treatment burdens associated with anticancer therapy in the population.

However, a mean of panelists was less confident that the conclusions can be applied to unlabeled use in patients:

  • Whose prostate cancer has not metastasized;
  • Who belong to demographic groups that may have been under-represented in clinical trials;
  • Who have metastatic, castrate-resistant disease and symptoms more severe than minimally symptomatic; or
  • Who have metastatic prostate cancer but have not failed hormonal therapy.

During discussion, the panel generally agreed there is not adequate evidence to identify patients more or less likely to respond to Provenge based on factors such as hemoglobin levels or pain.

It also discussed evidence gaps regarding the health outcomes attributable to treatment.
“There is a great need to figure out the best way to coordinate this immunotherapy with chemotherapy,” Robert Steinbrook, adjunct associate professor of medicine at Dartmouth Medical School, said.

Ravi Madan, assistant clinical investigator at the National Cancer Institute, suggested studies of earlier disease states, such as pre-metastatic, and investigations of combination therapies and sequences of therapies.

Responding to a panelist’s question on Provenge supply, Mark Frohlich, Dendreon’s chief medical officer, said Dendreon is building new capacity, and the company should be ready to meet demand by the middle of next year.

The MEDCAC meeting was scheduled after CMS in late June opened a national coverage analysis for Provenge, which was approved in April, to determine if the agency adopts a national policy to pay for the treatment, which costs $93,000 for a treatment course (DID, July 2).

A proposed coverage decision is due next March and a determination is expected by June 30. — April Hollis


FDA Backs Solicitor General in Generic Drug Preemption Cases

Federal regulations do not categorically preempt a plaintiff’s “failure-to-warn” claims against generic drugmakers, because manufacturers are obligated to inform the FDA of risks that may warrant a labeling change, the agency says in an amicus brief filed this week with the U.S. Court of Appeals for the Sixth Circuit.

In the brief, the FDA says that although generic companies are prohibited from effecting changes to the labeling of their products that diverge from the brand drug label, they could have requested the agency coordinate appropriate warning letters to physicians or take other steps to address the labeling concerns.

“State law may not impose liability on an ANDA holder for failing to send such a letter unilaterally. But an ANDA holder certainly may provide FDA with any information it believes warrants such a letter,” the agency says.

Moreover, the ANDA process requires applicants to notify the FDA about new safety information they believe should be added to a product’s generic and brand labeling, the agency says.

The agency’s position on generic preemption mirrors that of the Solicitor General in an amicus brief filed last month with the Supreme Court (DID, Nov. 5).

The case involves three consolidated appeals alleging that generic and brand versions of Wyeth’s gastroesophageal reflex drug Reglan (metoclopramide HCI) failed to adequately warn of the risk of tardive dyskinesia with long-term use.

In each case, a district court ruled in favor of the drugmakers, saying the plaintiff’s failure-to-warn claims were preempted by federal law.

The FDA disagreed, saying that while “federal law may circumscribe the possible theories of recovery by plaintiffs, it does not present an outright bar to recovery.”

Further, the FDA says that making generic drugmakers liable for failure-to-warn claims does not weaken the Hatch-Waxman Amendments, since the intent is not to pursue low-cost generic drugs at any cost.

The FDA’s amicus brief is available at www.fdanews.com/ext/files/Metaclopramide-FDAAmicusrePreemption112010.pdf. — Meg Bryant


Waxman Urges Change to 12-Year Exclusivity Period for Biologics

Rep. Henry Waxman (D-Calif.) is vowing to amend the 12-year period of exclusivity granted to manufacturers of brand biologics in healthcare overhaul legislation earlier this year.

Saying he is “profoundly disappointed” by the policy, Waxman said Wednesday at the World Generic Medicines Congress Americas 2010 in Washington that the legislation as written would not help to lower the cost of biologic drugs and he would fight to have it changed.

“The legislation did not balance appropriately the incentives for innovation with the incentives for competition,” Waxman, Chairman of the House Committee on Energy and Commerce, said. “This was clearly an opportunity lost.”

Waxman, along with President Barack Obama, had been among those pushing for a 7-year period of exclusivity, arguing that a longer exclusivity period before biosimilar competition begins would harm patients and diminish innovation (DID, June 26, 2009).

That stance received significant pushback from the brand pharmaceutical industry, however, as well as from members of Congress, including Rep. Anna Eshoo (D-Calif.).

Despite a last-minute effort from Waxman and Obama, the 12-year period eventually made it into the final bill (DID, Jan. 15).

Waxman has long been among the generic-drug industry’s biggest allies in Congress, but with Republicans set to take control of the House in January, he acknowledged that it will be difficult for himself and other Democrats to advance legislation.

Still, Waxman said he will continue to press his case on several issues, with a legislative ban on pay-for-delay settlements also in his sights.

The deals are “a win-win for the brand and generic firms, but a loser for the public who will have to continue paying monopoly prices,” Waxman said. “Too frequently, these agreements are anti-competitive and improperly postpone generic entry.”

Legislation that would prohibit the deals is pending in the Senate. However, legislators from both parties have written to Senate Majority Leader Harry Reid (D-Nev.) urging him not to pursue the measure (DID, Nov. 1). — David Belian


Citing Cracked Vials, Anthera Suspends Dosing in Lupus Trial

Cracked vials may set back Anthera Pharmaceuticals’ development plans for its lupus candidate, A-623.

The company decided to suspend enrollment and dosing in the Phase IIb PEARL-SC trial after a site in the U.S. reported a number of cracked vials of the study product. A preliminary inspection of the site’s inventory and the company’s product storage facilities revealed the cracking was not an isolated problem, Anthera CEO Paul Truex said late Tuesday in a conference call.

Anthera notified the FDA of the problem Tuesday morning and is waiting for the agency’s response so it can develop short- and long-term plans to move forward.

The trial was initiated in August, so fewer than 30 subjects had started dosing so far at sites in Colombia, Mexico, the Philippines and the U.S. There have been no reports of patient-related side effects attributed to the cracked vials and no serious adverse events, Truex said. A-623 is delivered subcutaneously and targets elevated levels of B-lymphocyte stimulator.

“Getting to the root of this issue and resuming the clinical program for A-623 is a top priority,” Truex said, adding that the trial will not resume until the problem is fully addressed.

Anthera’s investigation involves both its manufacturing and distribution facilities, and Truex promised a thorough inspection of 100 percent of the inventory and supply chain. The vials are being analyzed by a lab to determine why they cracked.

“We’re going to move mountains to get things answered as quickly as possible,” Truex said.

There is no evidence that the problem is with the drug itself, Anthera’s Chief Financial Officer Chris Lowe told DID Wednesday. It appears to be more of a physical problem with the vials, he added.

The inspection of all product should be completed in the next few weeks, he noted, and the lab results are expected within a month, if not sooner. By then, the company should know what steps the FDA wants it to take to resume the trial.

Truex listed three possibilities: The agency could ask for a Type A meeting, request data for an IND or place a hold on the trial.

Although the PEARL-SC trial is a Phase IIb, Anthera had hoped it could be one of two pivotal trials for the drug, Lowe said. The trial is modeled on the BLISS studies Human Genome Sciences and GlaxoSmithKline used for their lupus drug Benlysta, which received overwhelming support from an advisory committee Tuesday (DID, Nov. 17).

The worldwide PEARL-SC trial is to enroll up to 600 lupus patients in three dosing arms and a control arm. The primary endpoint is based on the Systemic Responder Index, the same as for Benlysta, Lowe said.

The trial has two components: a 24-week treatment and an optional safety extension. Anthera had expected to have results from the first component by the first quarter of 2012, Lowe said, adding that it’s too soon to tell how long the trial may be delayed because of the vial issue.

Although the company has other products in clinical trials, they are oral drugs, so they will not be affected by the cracking problem, Lowe said.

While he is not aware of cracked vials in other clinical trials, Truex noted that several drugmakers have had similar problems with marketed products. For instance, Johnson & Johnson subsidiary Ortho Biotech recalled more than 44,000 vials of the erythropoiesis-stimulating agent Procrit in 2008 because of cracks found in a small number of vials (DID, Aug. 7, 2008). — Mari Serebrov


FDA Target of Contempt Motion Over Access to Plan B

The Center for Reproductive Rights (CRR) has filed a motion for contempt against the FDA for failing to obey a court order to reconsider restricting OTC access to Teva’s emergency contraceptive Plan B.

The CRR argues that the agency has not made any meaningful efforts to comply with a March 2009 order to reconsider its denial of OTC Plan B (levonorgestrel) use by women younger than 17, according to the motion filed Tuesday in the U.S. District Court for the Eastern District of New York.

In April 2009, however, the FDA lowered the minimum age for Plan B access to 17.

“The FDA has patently ignored the order and has continued its administrative stall” on the CRR’s 2001 citizen petition, the motion says. That petition asked the FDA to give OTC status to Plan B, which was granted in 2006.

It notes that in August, the FDA “indicated that it has no plans to rule on the citizen petition any time soon” and believes the best way to comply with the order is to wait for an sNDA “that may or may not be filed at some unknown point in the future” and would include OTC access to women of all ages.

Despite the motion, the FDA still feels an sNDA is the best way to comply with the order, agency spokeswoman Karen Riley told DID Wednesday.

The FDA has stated Teva plans to file an sNDA regarding use by women younger than 17, according to the motion. But the CRR is requesting that the court act now to:

  • Schedule oral arguments on the motion;
  • Hold the FDA in contempt of the court order; and
  • Direct the FDA to issue a ruling on the citizen petition within 45 days of the court’s ruling on the motion.

The CRR first took the FDA to court in 2005 in Tummino v. von Eschenbach after the agency refused to rule on the citizen petition.

In 2009, the court found the FDA had acted in “bad faith and in response to political pressure,” not science, when it delayed making a decision, and that it had departed from its normal procedures (DID, March 24, 2009). The court told the FDA to reconsider whether to approve a switch to OTC status without age or point-of-sale restrictions.

The motion, filed in Tummino v. Hamburg, is available at www.fdanews.com/ext/files/MemSupportMotionContemptFINAL111610.pdf. — April Hollis

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