DID - Sept. 15, 2008 Issue

Vol. 7 No. 180

Merck’s Gardasil Vaccine Gets Expanded Indications

The FDA approved the use of Merck’s human papillomavirus (HPV) vaccine Gardasil to prevent vulvar and vaginal cancer, according to a Sept. 12 approval letter.

Gardasil had been approved to prevent cervical cancer. Other indications for precancerous or dysplastic lesions, including vaginal, cervical and vulvar neoplasias remain unchanged. 

“There is now strong evidence showing that this vaccine can help prevent vulvar and vaginal cancers due to the same viruses for which it also helps protect against cervical cancer,” Jesse Goodman, director of CBER, says in a statement. “While vulvar and vaginal cancers are rare, the opportunity to help prevent them is potentially an important additional benefit from immunization against HPV.”

Gardasil’s labeling was updated to note that “available information is insufficient to support use beyond age 26, the current FDA-approved age,” the agency says. “Also, new information has been added showing that Gardasil does not protect against diseases caused by HPV types not contained in the vaccine.”

Merck previously received a complete response letter from the FDA regarding an expansion of the Gardasil patient population for women age 27–45 (DID, June 26). — Christopher Hollis


CDASH Version 1.0 Set for Publication This Month

The Clinical Data Interchange Standards Consortium (CDISC) hopes to publish the first version of its Clinical Data Acquisition Standards Harmonization (CDASH) initiative by the end of September.

“We’re in a conference room right now trying to finalize the standard,” Project Director Rhonda Facile told DID last week. She said the working group has received 1,800 public comments and is trying to take them all into account.

The goal of the initiative goal is to allow research sites to report data in a consistent format, even when sponsors use incompatible systems. CDISC is a global nonprofit organization whose goal is to promote interoperability. Since the FDA began asking drug companies to use the organization’s Study Data Tabulation Model (SDTM) for esubmissions, the industry increasingly has fallen into line.

The availability of CDASH will help to “some extent” with a common complaint of researchers — that they have to maintain more than one incompatible electronic data capture system, sometimes on different computers for different sponsors, Andrew Newbigging, vice president for integrations development at Medidata Solutions Worldwide, told DID. The company is an electronic data capture (EDC) and clinical data management provider.

“For example, entering vital signs data would be set up the same way in different systems although that wouldn’t address different designs [of various EDC systems], such as different ways of navigating,” he noted.

Earlier this year, Medidata obtained certification in CDISC’s Operational Data Model (ODM), which provides a format for representing the study metadata, study data and administrative data associated with a clinical trial.

The certification covers all the existing “use cases” of ODM. Examples of common ODM use cases are lab-data transfer, the ability to browse case report forms, transfer of data between a contract research organization and a sponsor, and multiple data vendors sending segments of data to a sponsor. — Martin Gidron


ImClone Turns Down Bristol-Myers Squibb Offer

ImClone Systems Chairman Carl Icahn turned down Bristol-Myers Squibb’s (BMS) $60-per-share offer in an open letter and invited BMS CEO and Chairman James Cornelius to increase his bid.

ImClone rejected the BMS offer as inadequate and says it has not yet determined whether a higher offer from an unnamed “large pharmaceutical company” for $70 per share in cash “would be adequate.”

BMS already owns 17 percent of the company and holds long-term marketing rights in the U.S. to ImClone’s Erbitux (cetuximab). BMS said ImClone was worth approximately $4.5 billion as of July 31 (DID, Aug. 1). ImClone representatives declined to comment on the total dollar amount for the $60-per-share BMS offer.

The offer from the unidentified bidder for the 83 percent stake in ImClone not held by BMS would be “subject to due diligence but not subject to financing,” ImClone says in a statement.

Cornelius wrote a letter about the $70-a-share bid to Icahn, in which he says the BMS board is “disappointed … that ImClone’s special committee unilaterally rejected our offer without discussing its merits with us and our advisors.” He adds that the new takeover bid for ImClone would have to undergo due diligence while the BMS offer “is not subject to due diligence and has been fully disclosed to ImClone’s stockholders.”

BMS “holds the exclusive long-term marketing rights in the United States to Erbitux [cetuximab] and related compounds, including IMC-11F8,” Cornelius writes, and “has no intention of agreeing to any modifications to these rights.” Moreover, he advises Icahn to “understand that our offer is for the entire company, and any potential restructuring of the company could severely jeopardize ImClone’s value and deprive ImClone’s stockholders of the benefits of our offer.”

Icahn replied last week that the July 31 offer had been unsolicited and that BMS had not sought “to have a conversation first” about it. He claims to have “tried to reach [Cornelius] to discuss our position before we made it public.”

As for the rights to IMC-11F8, which could compete with Erbitux if approved, “we disagree that [BMS’] rights are clear and do not waive any rights that we may have with regard thereto,” Icahn writes. “With respect to a potential restructuring of ImClone, rest assured that we will act in what we consider the best interests of all our shareholders and not just [BMS].” — Martin Gidron


Report: US Market for Neuropathic Pain, Fibromyalgia to Double

The market for drugs that treat neuropathic pain associated with such conditions as herpes, diabetes and fibromyalgia is valued at $2.6 billion in the U.S. and will top $5.1 billion in 2018, according to a market research firm.

There are 4.7 million patients with neuropathic pain in the U.S., and the population is expected to grow to 6.1 million by 2018, according to the report issued by WWMR.

Sales growth during the next five years is expected to be driven by prescriptions for drugs to treat fibromyalgia, WWMR says in a statement. The research firm notes Pfizer’s Lyrica (pregabalin) and Eli Lilly’s Cymbalta (duloxetine HCl) have been approved for fibromyalgia and diabetic neuropathic pain.

WWMR cites two other drugs under review by the FDA to treat fibromyalgia and neuropathic pain. “Forest Laboratories and Cypress Biosciences’ antidepressant milnacipran and Schwarz Pharma’s lacosamide (Vimpat), a sodium ion channel antagonist/CRMP2 modulator, will compete for market share as well as provide the benefit of an additional mechanism of action,” the company says.

Schwarz has submitted an NDA to the FDA for lacosamide to treat neuropathic pain, and a milnacipran application is awaiting FDA approval for fibromyalgia.

“Worldwide, approximately 76 agents are in active clinical trials for the treatment of neuropathic pain,” WWMR writes. In addition to lacosamide and milnacipran, three new neuropathic pain treatments are registered or pre-registered with the FDA for marketing approval:

  • NeurogesX’s transdermal capsaicin;
  • GW and Bayer’s dual cannabinoid receptor agonist; and
  • Cephalon’s buccal fentanyl. — Christopher Hollis


CV Therapeutics Taps Menarini to Market Ranexa in Europe

Menarini will pay CV Therapeutics $70 million upfront and $385 million in potential developmental and commercialization milestone payments for the rights to market CV’s angina drug Ranexa in 63 countries, including the 27 EU nations and Russia.

About two-thirds of the additional $385 million is for sales and development milestones, such as new indications, with one-third for the number of promotion and detailing commitments, Louis Lange, CEO for CV Therapeutics, said Friday in a conference call.

In addition, Menarini will pay CV Therapeutics “significant double-digit” royalties on Ranexa (ranolazine) sales, Lange said.

“Our strong label in Europe provides Menarini with an excellent platform for success,” Lange said. “The approved Ranexa labeling in Europe highlights first-in-class, late sodium-channel effects … including data showing statistically significant reductions” in ventricular tachycardia.

He expects Menarini to launch the drug in the UK and Germany in the first quarter of 2009 and says treatment would cost from $2.80–$4.25 a day in big European markets. The drug’s price in Europe may be higher because it is approved as an add-on therapy for patients whose stable angina pectoris is inadequately controlled or who are intolerant of first-line anti-anginal therapies, Lang said.

The angina market in Europe, with 13.5 million patients, is probably larger than in the U.S., according to Lang. Strong growth of the drug’s sales in Turkey and Russia also is expected.

“This product label clearly differentiates Ranexa in a large market with declining rates of stent use and should allow for broad patient acceptance,” he said.

Menarini had the fourth-largest sales force in Europe with 6,000 representatives, Lang said. The firm makes 9 million sales calls annually, he noted. Ranexa is expected to be in the leading position for Menarini sales representatives, 1,000 of whom will detail the product during the first year of the agreement.

Menarini, which recorded $2.5 billion in sales for 2007, has a strong cardiovascular and metabolic sales organization — marketing products such as Pfizer’s Lipitor (atorvastatin calcium) and AstraZeneca’s Nexium (esomeprazole magnesium) in Europe, Lange said.

Ranexa was approved by the FDA two years ago to treat patients with chronic angina who did not respond adequately to other treatments (DID, Jan. 31, 2006).

CV Therapeutics previously said the FDA would miss a July 27 user fee date for an sNDA that requested expanded labeling for Ranexa. The company wants to market the drug as a first-line treatment for angina patients. The application also includes claims for reductions in hemoglobin A1c and ventricular arrhythmias in patients with coronary artery disease.

During the conference call, Lang said the firm was in labeling discussions with the FDA and expects the sNDA to be approved later this year. Ranexa had $25.4 million in sales during the second quarter of 2008, the company says, but Lang predicted the drug could become a blockbuster in Europe without additional indications. — Christopher Hollis


Takeda Files Lawsuit Against Taiyo Over Recall

Japan’s Takeda Pharmaceutical is suing Taiyo Pharmaceutical Industry for damages related to a recall of injectable antibiotics.

A piece of glass was found in a vial of Pansporin (cefotiam HCl), which had been manufactured for Takeda under a contract with Taiyo Pharmaceutical. Takeda recalled other lots when it could not rule out the possibility of more glass. The drugs were recalled last year in May and June, according to the suit filed in the Osaka District Court.

Takeda alleges that Taiyo failed to implement sufficient quality control procedures to prevent the commingling of glass in the production process and did not prepare and maintain production records that would allow identification of defective products.

Takeda had been in discussions with Taiyo regarding roughly $26 million in damages it had wanted as a settlement. The companies were unable to reach an agreement.

Takeda says it now produces all of its injectable antibiotics at its Hikari plant in Yamaguchi Prefecture. — Elizabeth Jones


Sun Gets Approval for Generic Fosamax

The FDA has granted final approval for Sun Pharmaceutical Industries’ ANDA for generic Fosamax in 5-, 10-, 35- and 70-mg strengths.

Merck’s Fosamax (alendronate sodium) tablets are used to treat glucocorticoid-induced osteoporosis and Paget’s disease, to increase bone mass in men with osteoporosis and to prevent or treat postmenopausal osteoporosis.

Fosamax tablets have annual sales of roughly $560 million in the U.S., according to Sun.

Merck lost patent protection for Fosamax in February, and Barr Pharmaceuticals and Teva Pharmaceutical Industries subsequently shared 180-day marketing exclusivity (DID, Feb. 6).

Several other companies have approval for generic Fosamax tablets, including Aurobindo Pharma, Mylan Laboratories and Watson Pharmaceuticals, which sold the authorized generic version in 35- and 70-mg strengths. — Elizabeth Jones

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