DID - Nov. 20, 2009 Issue

Vol. 8 No. 227

Jury Sides With Novartis in Generic Famvir Patent Case

Novartis has won a patent dispute in a district court with Teva Pharmaceutical Industries over the antiviral drug Famvir, which could make Teva liable for damages due to its short-lived at-risk 2007 launch of a generic version.

A jury in the U.S. District Court for the District of New Jersey decided that Novartis’ patent on Famvir (famciclovir) was not invalid based on obviousness and that the drugmaker did not withhold or misrepresent information to the PTO, according to court documents filed last week.

Teva did not provide clear and convincing evidence that an individual with ordinary skill in the art would have chosen Novartis’ Denavir (penciclovir) as a lead compound as Novartis did, been motivated to modify penciclovir to make famciclovir, or expected its successful properties, according to the verdict. The jury also cited unsuccessful attempts by others to find the solution provided by the patent indicated that the patent was not obvious.

Novartis sued Teva for patent infringement in 2005, the same year the generic-drug maker filed an ANDA containing a Paragraph IV certification on Novartis’ ’937 patent for Famvir.

Teva received final approval from the FDA in August 2007 to market generic Famvir tablets in the U.S. (DID, Aug. 28, 2007). The U.S. Court of Appeals for the Federal Circuit issued an injunction prohibiting Teva from selling its generic version of the drug a month later (DID, Sept. 11, 2007).

The jury also found that Teva did not provide evidence that Novartis knowingly withheld or misrepresented information to the PTO or intended to deceive the patent examiner in the case, and thus found that there was no inequitable conduct committed in the prosecution of the ‘937 patent, as Teva had tried to claim.

Novartis is encouraged by the jury’s advisory decision the company did not commit inequitable conduct and hopes that the judge reflects this in his final ruling, it says in a statement. Teva did not respond by press time to requests for comment.

The verdict in Novartis Pharmaceuticals Corporation, Novartis Pharma AG and Novartis International Pharmaceutical Ltd., v. Teva Pharmaceuticals USA, Inc. was filed Nov. 18. — David Belian


FDA Delays NDA Review for Exalgo Extended-Release Tablets

CDER pushed back the Prescription Drug User Fee Act action date for Mallinckrodt’s Exalgo extended-release tables until Feb. 22, to review new information.

The information submitted Nov. 18 is considered a major amendment to the NDA for Exalgo (hydromorphone HCI), Mallinckrodt’s parent company, Covidien, says in a statement Friday. The original date was Nov. 22. Covidien declined to discuss details of the data.

Mallinckrodt and Neuromed are seeking approval of Exalgo for once-daily use in managing moderate-to-severe pain in opioid-tolerant patients who require extended therapy. Neuromed developed Exalgo and filed an NDA in February. Mallinckrodt bought the rights to the drug in June.

The FDA’s Anesthetic Life Support Drugs and Drug Safety and Risk Management advisory committees met jointly in late September to compare Exalgo with other opioid drugs (DID, Sept. 24). During the meeting, evidence was presented that showed the drug is modestly stronger than the painkillers hydrocodone and oxycodone.

Although the committee took no votes, it determined that Exalgo is effective in treating certain patients but poses significant potential for abuse. The product has a risk evaluation and mitigation strategy (REMS) that the committee found acceptable as long as the strategy is phased in to assess the product’s use by particular practitioners and specific disease types. Doing so would ensure the product has a sustained presence on the market, committee chairman Jeffery Kirsch said at the meeting.

In February, the FDA told 16 drug companies that it would require REMS to reduce abuse of opioid pain medications (DID, Feb. 10). — Meg Bryant


Contamination Cited in P&G Recall of Vicks Sinex Products

Procter & Gamble (P&G) is conducting a voluntary recall of three lots of Vicks Sinex nasal spray after finding the bacteria Burkholderia cepacia in a small amount of product.

The contamination was discovered during routine quality control in a U.S. lot imported from the company’s Gross Gerau, Germany, facility, the company says in a statement Thursday. P&G is testing UK and German lots produced from a single batch of raw material mixture.

A thorough investigation is under way to establish the root cause, spokesman Paul Fox told DID. He noted the issue seemed to be limited to the three lots and that P&G was working closely with the FDA and other regulators.

There have been no reports of illness, but B. cepacia could cause serious infections in patients with a compromised immune system or chronic lung conditions, the statement says.

The products involved in the recall are:

  • Vicks Sinex (oxymetazoline HCl) VapoSpray 12-hour Decongestant UltraFine Mist, 15 mL, distributed in the U.S.;
  • Vicks Sinex Micromist Aqueous Nasal Spray Solution, 15 mL, distributed in the UK; and
  • Wick Sinex Schnupfenspray Dosiersystem, 15 mL, distributed in Germany.

A recent FDA analysis of recalls shows drugmakers may be ignoring B. cepacia, which was cited in a warning letter this year to Sage Products (DID, Feb. 5). Contamination with the same bacteria was cited as the reason for a recent Tylenol recall by a Johnson & Johnson subsidiary (DID, Sept. 25).

Industry generally does not consider product contamination with B. cepacia a major problem because there is a low risk to healthy people, Lynn Torbeck, contractor for the FDA’s recall root cause research project, said at the Parenteral Drug Association–FDA 2009 Joint Regulatory Conference in Washington, D.C., in September. — April Hollis


FDA Debars Two Clinical Investigators, One for Selling Counterfeit Drugs

The FDA is permanently barring two clinical investigators from participation in studies to support drug product applications because of their felony convictions.

The clinical investigators, Niaja Kane and Anthony Albanese, were convicted in separate cases of drug-related felonies under federal law, according to the debarment notices slated to be published in the Federal Register Nov. 23 that take effect the day of publication.

Kane pleaded guilty in January 2007 in the U.S. District Court for the Eastern District of Pennsylvania to trafficking in counterfeit goods, holding counterfeit drugs for sale with the intent to defraud and attempted possession with intent to distribute counterfeit controlled substance. The case involved 2,040 tablets of fake Viagra (sildenafil citrate) and 1,200 tablets of counterfeit Cialis (tadalafil), both for erectile dysfunction, as well as 2,333 7.5-mg and 6,573 10-mg tablets purported to be the painkiller Percocet (oxycodone HCl/acetaminophen).

In addition, the counterfeit Percocet that Kane attempted to sell contained oxycodone, a Schedule II controlled substance, the debarment order says.

Anthony Albanese was convicted in November 2004 in the U.S. District Court for the District of Rhode Island of four counts related to the sale of drug samples: conspiracy to sell drug samples, unlawful sale of drug samples, healthcare fraud and money laundering.

According to the debarment order, Albanese “paid cash and goods” to a physician for samples that were then removed from their packaging and resold as prescription drugs at Albanese’s pharmacy from July 2000 to August 2002.

The FDA sent Kane and Albanese separate notices Aug. 13 proposing permanent debarment, and both of them failed to respond, the Federal Register notices say.

The debarment order against Niaja Kane can be found at www.fdanews.com/ext/files/2009-28083_PI.pdf. The order disbarring Anthony Albanese is available atwww.fdanews.com/ext/files/2009-28084_PI.pdf. — Meg Bryant


GSK Recalls One Lot of H1N1 Vaccine Over Anaphylaxis Concerns

GlaxoSmithKline (GSK) is recalling one lot of its influenza A (H1N1) vaccine Arepanrix in Canada after a higher-than-expected number of reports of anaphylaxis in patients given vaccine from that lot compared with other patients.

GSK is investigating the reports with Health Canada and the Public Health Agency of Canada and advises healthcare providers to set aside vaccines from lot No. A80CA007A until the investigation is complete, the company told DID Friday.

Generally, the frequency of anaphylaxis following immunization is less than one per 100,000 doses, the company said, adding this does not exceed the rates reported for other vaccines. Common side effects include swelling, redness or pain at the injection site. Fever, headache, fatigue and muscle aches have been reported less frequently.

At least some rare adverse reactions, not detectable during clinical trials, can occur with H1N1 pandemic vaccine campaigns, underscoring the need for rigorous safety monitoring, the World Health Organization (WHO) said last week in a statement. The frequency of reactions that have been reported is well within the expected range, the WHO added. — April Hollis


Pfizer’s Injectable Pulmonary Drug Revatio Wins Approval

The FDA has approved Pfizer’s injectable formulation of the pulmonary arterial hypertension (PAH) drug Revatio.

Revatio (sildenafil) injection is indicated for continued treatment of patients who have been prescribed Revatio tablets but are temporarily unable to take oral medication, Pfizer says in a statement Nov. 20.

Revatio is indicated to improve exercise ability and delay clinical worsening of the disease for adult PAH patients. It was approved in 2005 (DID, June 7, 2005). Pfizer’s drug is the only FDA-approved phosphodiesterase-5 inhibitor available in both tablet and intravenous formulations, the company says.

Third-quarter sales of Revatio worldwide rose 18 percent to $111 million compared with $95 million in the same quarter in 2008, according to a company earnings report.

Also Friday, the FDA approved a new indication for Pfizer’s antipsychotic Geodon (ziprasidone HCl) as an adjunctive maintenance treatment with lithium or valproate for bipolar I disorder in adults, according to the company’s statement. — April Hollis


EMEA Warns of Risks Associated With MRI Scan Drugs

Manufacturers of contrast agents containing gadolinium that are used for magnetic resonance scans are being asked to revise the drug labeling to warn of the risk of patients developing nephrogenic systemic fibrosis (NSF), the European Medicines Agency (EMEA) says.

The recommendation was issued by the agency’s Committee for Medicinal Products for Human Use (CHMP) after its review of the association between the drugs and NSF, a rare condition characterized by thickening of connective tissues in the skin, joints, muscles and internal organs in patients with severe kidney problems, the EMEA says in a statement Friday. The drugs are used to prepare patients for MRIs and magnetic resonance angiography.

The committee classified drugs carrying the highest risk including: Mallinckrodt’s Optimark (gadoversetamide), GE Healthcare’s Omniscan (gadodiamide), Bayer Healthcare’s Magnevist (gadopentetate dimeglumine), and Insight Agents’ Magnegita (gadopentetate dimeglumine), according to the statement. The CHMP recommends the drugs be contraindicated for newborns younger than four weeks, patients with severe kidney impairment, and patients who are scheduled for or have recently received a liver transplant.

New warnings should be added to prescribing information for medium- and low-risk drugs, including Epix Pharmaceuticals’ Vasovist (gadofosveset trisodium), Bayer Schering Pharma’s Primovist (gadoxetate disodium), Bracco’s MultiHance (gadobenate dimeglumine), Guerbet’s Dotarem (Gd-DOTA), Bracco’s ProHance (gadoteridol) and Bayer Schering Pharma’s Gadovist (gadobutrol), the committee recommends. The labeling should warn of the risk of the drugs’ use in liver-transplant patients and those with severe kidney damage. The committee also recommends patients be screened for kidney damage before receiving the drugs.

Prescribing information for all gadolinium-containing contrast agents should:

  • Warn that the elderly may be at particular risk of NSF due to impaired ability of their kidneys to clear gadolinium from the body;
  • State that there is no evidence to support the initiation of kidney dialysis to prevent or treat NSF in patients not already undergoing the procedure; and
  • Recommend that the type and dose of contrast agent used should be recorded.

Despite the warnings, CHMP still considers the drugs to have a positive risk-benefit ratio but recommends that further studies be carried out on the long-term retention of gadolinium in human tissues. — David Belian

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