DID - Aug. 20, 2009 Issue

Vol. 8 No. 162

Lilly Stops Development of Arzoxifene After Trial Results

Eli Lilly has decided not to seek regulatory approval for its osteoporosis treatment arzoxifene, citing its failure to meet secondary endpoints in a five-year Phase III trial and more frequent reports of some adverse events.

Patients taking the drug reported more frequent effects, including venous thromboembolism and hot flushes, compared with those taking a placebo, the company says.

The FDA’s potential consideration of the drug’s efficacy also was a factor, Teresa Shewman, a Lilly spokeswoman, told DID Wednesday. “We certainly knew what would be required for an osteoporosis treatment to be beneficial for patients,” she said.

Arzoxifene met the Phase III trial’s primary endpoint of significantly reducing the risk of vertebral fracture and invasive breast cancer in postmenopausal women, but it did not demonstrate a statistically significant difference compared with a placebo in secondary efficacy endpoints, including nonvertebral fractures, clinical vertebral fractures, and cardiovascular events, Lilly says in a statement this week.

The combination of the study results and the availability of other osteoporosis treatments also led the company to decide not to pursue arzoxifene development, Shewman said.

“It was the overall clinical profile of the compound,” Shewman said. “We took into consideration the study involved. We also took into consideration other therapeutic options out there, including Lilly’s own osteoporosis treatments.”

The decision to abandon the compound at such a late stage of development is a reminder of the high risks associated with pharmaceutical innovation, John Lechleiter, Lilly’s chairman and CEO, says in the statement. The company refused to disclose how much money had been spent on arzoxifene’s development, but Shewman said the average cost for the company to bring a new molecule to market is $1.2 billion. — David Belian


Teva Loses Court Bid to Sell Generic Singulair Before 2012

Teva Pharmaceuticals USA won’t be able to win FDA approval for a generic version of Merck’s blockbuster allergy drug Singulair until August 2012 after a federal judge ruled that it had infringed a patent on the product.

U.S. District Court for the District of New Jersey Judge Garrett Brown upheld Merck’s ’473 patent on Singulair (montelukast sodium) and ruled that Teva infringed the patent, in court documents filed Wednesday. Brown rejected Teva’s argument that the patent is obvious in light of prior art, saying the drugmaker hadn’t provided “clear and convincing evidence,” according to court documents.

Teva maintained Merck had failed to submit relevant prior art when it applied for the patent. Brown was not persuaded that Merck had committed inequitable conduct and ruled that the prior art in question “is only slightly, and not highly, material,” according to court documents.

The court ruled the Singulair patent is valid in the U.S., Bruce Kuhlik, executive vice president and general counsel of Merck, says in a statement Wednesday. “We invest heavily in the R&D that is needed to discover innovative medicines like Singulair, and we will vigorously defend our intellectual property rights.”

Teva is reviewing the court’s decision to determine its next course of action, the company says in an Aug. 19 statement.

The ’473 patent is being reviewed by the PTO as a result of a request by Article One Partners, an online group that looks for evidence that can legitimize or invalidate selected patents (DID, June 1). If the PTO decides further action is warranted, it may amend or revoke the claims in the patent — a decision Merck can appeal to the Court of Appeals for the Federal Circuit.

The Singulair franchise had worldwide sales of about $2.32 billion during the first half of the year, according to a Merck financial statement. Merck Sharp & Dohme Pharmaceuticals SRL v. Teva Pharmaceuticals, USA, Inc., et al. was filed in February 2007. — Elizabeth Jones


Sandoz, Medicis Settle Solodyn Patent Dispute

Medicis Pharmaceutical has agreed to settle a patent infringement suit with Sandoz over the acne drug Solodyn.

As part of the agreement, Sandoz acknowledged that the ’838 Medicis patent covering Solodyn (minocycline HCl) is valid and enforceable. Medicis in turn plans to drop its litigation against Sandoz.

Medicis filed a Solodyn-related citizen petition in February seeking 30-month stays of approval for generic versions of drugs containing old antibiotics to protect Solodyn sales (DID, March 19). The ‘838 patent expires February 2018.

Warner Chilcott, Roche and Stiefel Laboratories also submitted citizen petitions. They were seeking information on whether a 30-month stay of approval would be imposed on ANDAs that include a Paragraph IV certification on certain patents involving drugs that contain an old antibiotic. Such antibiotics were approved by the FDA before the Nov. 21, 1997, effective date of the FDA Modernization Act (FDAMA).

Data on the antibiotic patents at issue were submitted to the FDA after the generic companies had submitted their ANDAs.

The other products in question include Warner Chilcott’s Doryx (doxycycline hyclate) and Stiefel’s Evoclin (clindamycin phosphate), which are used to treat acne, and Roche’s Cellcept (mycophenolate mofetil), which is used to prevent organ rejection.

The FDA rejected the brand companies’ arguments, saying the drugmakers were applying Hatch-Waxman as it was originally written, not as revised by subsequent legislation.

Medicis filed the suit, Medicis Pharmaceutical Corporation v. Mylan Inc., et al., in the U.S. District Court for the District of Delaware Jan. 13 against Teva Pharmaceutical Industries’ Barr Laboratories subsidiary. The suit also named Mylan and Matrix Laboratories. Teva has already settled with Medicis (DID, March 20). — Elizabeth Jones


Par Partner Gets FDA Approval for Oral Yeast Infection Treatment

The FDA has accepted an NDA for Lauriad tablets to treat oropharyngeal candidiasis (OPC) from Strativa Pharmaceuticals, a Par Pharmaceutical subsidiary.

Lauriad (miconazole) would be the first oral miconazole therapy available in the U.S., John MacPhee, Strativa’s president, says in a statement. The NDA submission for Lauriad mucoadhesive buccal tablets was based primarily on data from a Phase III study demonstrating that the product was not inferior to Bayer HealthCare’s Mycelex (clotrimazole) lozenges in the complete resolution of signs and symptoms of OPC, according to Par’s statement Wednesday.

The randomized, double-blind, double-dummy study was conducted in 577 HIV-positive patients in 40 sites in the U.S., Canada and South Africa. In a double-dummy study, participants receive a mix of active and inactive product.

The drug’s delivery system and daily dosing will be an effective alternative to therapies that must be taken in several doses a day, MacPhee added.

Strativa will be the exclusive U.S. distributor of the product under a licensing agreement with BioAlliance Pharma. Upon FDA approval of the product, Strativa will pay BioAlliance $20 million, as well as a royalty on future net sales, Par says in the statement.

Miconazole MBT has been approved in 11 countries and is marketed in France, Germany and the UK under the trade name Loramyc.

Separately, Par is ready to begin shipping a generic version of Boehringer Ingelheim’s Catapres TTS (clonidine), a transdermal patch to treat hypertension, after its partner Aveva Drug Delivery Systems received final FDA approval for the product.

The product is the first generic seven-day patch indicated to treat hypertension, and Par has exclusive U.S. rights to market, sell and distribute the generic Catapres TTS, Par says in a statement Aug. 18. Aveva will manufacture the patch and the companies will share profits.

Clonidine TDS is available in 0.1-, 0.2 - and 0.3-mg/day strengths and has annual U.S. sales of about $297 million, according to the statement, which cites IMS Health data. — Elizabeth Jones


Bayer Seeks Approval for New Levitra Formulation

Bayer Schering Pharma has begun applying worldwide for approval of a dissolvable tablet formulation of its blockbuster erectile dysfunction drug Levitra.

The company has submitted an application in Europe for regulatory approval of the new Levitra (vardenafil HCl) formulation, orally dissolving 10-mg tablets, and has begun submitting and translating documents for the application process in the U.S. and other countries, Yvonne Moller, a Bayer spokeswoman, told DID Wednesday.

“The documentation is already with the FDA, but we haven’t got the confirmation that they have everything together to start the process,” Moller said. The company expects to hear within weeks that the FDA has what it needs to begin reviewing the drug, she added.

The company also expects Australia’s Therapeutic Goods Administration to accept its filing for the new formulation this month, and it plans to launch the formulation in all of the countries where Levitra is being sold, Moller said.

Bayer expects prescriptions for the drug, which had sales of $243 million in the first half of 2009, to increase if the new formulation is approved but declined to estimate potential sales growth. — David Belian

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