Cephalon, Inc. (Nasdaq: CEPH) announced that it has filed a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) seeking approval to market a fentanyl effervescent buccal tablet for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy for their underlying persistent pain.
The tablet delivers the opioid fentanyl through the oral mucosa utilizing a proprietary enhanced absorption technology, OraVescent, developed by CIMA LABS INC., a wholly-owned subsidiary of Cephalon. Upon approval, Cephalon intends to commercialize OraVescent fentanyl (OVF) in multiple dosage strengths (100, 200, 400, 600, and 800 micrograms). The medication will be listed as a Schedule II controlled substance.

"Expanding our pain care franchise is integral to Cephalon's growth strategy," said Dr. Paul Blake, Executive Vice President, Worldwide Medical & Regulatory Operations. "With OVF, we build on our expertise in breakthrough pain to bring innovation to a clinically important, but often inadequately managed, component of chronic pain."

This NDA, submitted on schedule, is the fourth of five new product opportunities that Cephalon is pursuing over a 15-month period. A supplemental New Drug Application (sNDA) for ATTENACE(TM) (modafinil) Tablets [C-IV], for the treatment of attention-deficit / hyperactivity disorder in children and adolescents, and an NDA for NUVIGIL(TM) (armodafinil) Tablets [C- IV], for excessive sleepiness, were submitted for FDA review in December 2004 and March 2005, respectively. Cephalon recently entered into an agreement to develop and commercialize naltrexone long-acting injection for the treatment of alcohol dependence with Alkermes, Inc., which submitted an NDA for the product in March 2005. Cephalon also is conducting a Phase 3 clinical trial of GABITRIL(R) (tiagabine hydrochloride) as a treatment for generalized anxiety disorder.

The NDA submitted for OVF includes results from 13 studies. The pivotal double-blind, placebo-controlled, variable-dose study assessed the safety and efficacy of OVF compared with placebo in opioid-tolerant cancer patients with breakthrough pain. Patients treated with OVF showed a statistically significant improvement on the primary endpoint, the Sum of Pain Intensity Differences through 30 minutes (SPID30) (p <0.01). Interim safety analyses from three on-going Phase 3 trials in opioid-tolerant patients as well as pharmacokinetic data from nine clinical pharmacology studies are included in the submission. Safety data from 360 patients participating in the Phase 3 studies demonstrated that OVF was generally well tolerated.

Cephalon has drawn on its experience with ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] to develop a comprehensive Risk Minimization Action Plan (RiskMAP) for OVF, which was submitted with the NDA. FDA considers RiskMAPs integral to the commercialization and safe use of opioids.

Source: Cephalon

− Clinical Trials Evaluated Safety and Efficacy Data for Contraception as Well as Menses Inhibition −

Wyeth Pharmaceuticals, a division of Wyeth (NYSE:WYE), announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company’s New Drug Application (NDA) for a new combination oral contraceptive containing levonorgestrel/ethinyl estradiol with a first-of-its-kind dosing regimen. The product is designed to be taken every day, without a placebo phase and eliminates the menstrual cycle, and may offer some women, over time, the potential to eliminate the associated bleeding.  Wyeth is seeking market approval for the product for the prevention of pregnancy in women who elect to use oral contraception and who have no known contraindications for this method of contraception. If approved, this product will contain a low daily dose of ethinyl estradiol and levonorgestrel.

“This NDA is an important event in the evolution of oral contraceptives. No combination oral contraceptive is currently approved with this continuous, uninterrupted regimen,” says Dr. Ginger Constantine, Vice President, Women’s Health Care and Bone Repair, Wyeth Pharmaceuticals. “Wyeth developed this contraceptive so that women may have an additional option to manage their cycles. The studies to support this product are a reflection of our longtime commitment to innovation in women’s health.”

The NDA submission included data from two one-year Phase III clinical trials. These trials enrolled a total of 2,775 women and evaluated the safety and efficacy of the product for contraception. In addition, one of the secondary endpoints included was menses inhibition.  In the clinical trials, the more commonly reported adverse events included headaches, vaginal bleeding and cramps.

Filing an NDA with the FDA is an important step in the approval process in the United States.  Acceptance for filing does not indicate that approval has been or will be issued, nor does it represent an evaluation of the adequacy of the data submitted.

Source: Wyeth

Discovery Laboratories, Inc. (Nasdaq: DSCO) announces the results from a comparative pharmacoeconomic analysis of Surfaxin® (lucinactant) versus leading animal-derived surfactants (Survanta® and Curosurf®) in the prevention of Respiratory Distress Syndrome (RDS) in premature infants.  The data was presented at the 46th Annual Meeting (August 31 -– September 3) of the European Society for Paediatric Research (ESPR) in Siena, Italy.

Conclusions from the comparative pharmacoeconomic analysis are:

• Survival represents the largest component of aggregate cost of  care and a significant increase in survival was observed with  Surfaxin versus the animal-derived surfactants (mortality rates at 36 weeks post-menstrual age, 20.3% vs 24.1%, P=0.04,  respectively).
• Surviving premature infants treated with Surfaxin had 4.09 fewer  days in the Neonatal Intensive Care Unit (NICU), compared to the  surviving premature infants treated with animal-derived surfactants.
• The average inpatient costs were $130,280 for infants treated  with Surfaxin compared to $136,150 to infants treated with animal-derived surfactants, a cost savings of $5,870 per surviving premature infant.

Robert Segal, MD, Chief Medical Officer of Discovery Laboratories commented, "This is a very extensive comparative pharmacoeconomic analysis of surfactants in the prevention of Respiratory Distress Syndrome in premature infants.  As previously reported, Surfaxin has shown a significant survival advantage over the animal-derived surfactants based upon a pooled analysis of Discovery's SELECT and STAR clinical trials.  Not only does Surfaxin save babies' lives, but what is most impressive about these pharmacoeconomic outcomes is that Surfaxin reduces the cost associated with the care of these surviving babies.  Surfaxin has the potential to transform the treatment of Respiratory Distress Syndrome in the NICU."

Source: Discovery Laboratories

Targepeutics, Inc. announces that the company has entered into a license agreement with the National Institutes of Health (NIH) for commercial rights to ten US patents: Nos. 5, 614,191; 5,919,456; 6,518,061; 4,892,827; 5,696,237; 5,863,745; 6,051,405; 5,705,156; 5,512,658 and 5,328,984. Combined with Targepeutics' other exclusively licensed issued patents and several pending applications, these additionally patents give Targepeutics broad rights to commercialize its Genetically Engineered Interleukin 13 (IL-13) platform. The agreement was negotiated under the lead counsel of Jorge Goldstein of Sterne Kessler Goldstein & Fox PLLC.

The patents licensed from the NIH provide certain background rights for Targepeutics' Genetically Engineered IL-13 platform that includes its lead compound, Glioblast-13, a singly mutated IL-13 molecule combined with a derivative of Pseudomonas exotoxin. Glioblast-13 and further generations of mutated IL-13 of the entire platform were designed to be more specific, safe and potent than the wild type-based IL-13 compounds. Comparative studies performed to date have shown that the mutated IL-13 compounds have a safer and more potent therapeutic profile than wild type IL-13 based compounds.

Targepeutics' Genetically Engineered IL-13 platform is expected to yield more specific compounds with multiple mutations of the IL-13 molecule described in the recently issued patents. This platform will explore products for both therapeutic and diagnostic applications. The specificity and safety profile to date of these mutants opens up the possibility of treating cancers expressing the IL-13 receptor alpha 2, such as brain, pancreatic, head and neck, melanoma and gastric cancers. Targepeutics envisions using the targeting mutated IL-13's to carry cytotoxins or radiation to these cancers. These applications are currently hampered by the nonspecific nature of wild type IL- 13 based compounds that appear to target vital organs as well as tumors.

Targepeutics is a biopharmaceutical company developing selective molecularly targeted therapeutics to fight cancer. Currently, Targepeutics' three pharmaceutical platforms are Targepeutics' Genetically Engineered Interleukin-13, Immunotherapy (applications in cancer and asthma), and Anti- tumor Progression (targeting growth and ability of solid tumors to create new blood vessels). Targepeutics is based in Hershey, Pennsylvania and is privately held.

Source: Targepeutics

TheraQuest Biosciences, a development stage pain management company, announced that the FDA Office of Orphan Products Development has granted a second Orphan Drug Designation for TQ-1017, its abuse deterrent once-daily extended release tramadol for the management of postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a chronic, debilitating neuropathic pain syndrome that occurs as a complication of shingles or herpes zoster infection.

The pain of PHN is unrelenting and is often described as burning, stabbing or aching. According to Dr. Richard Payne, Professor of Medicine and Director, End of Life Care Institute at Duke University, "In addition to persistent pain, patients with PHN experience episodic pain due to abnormal sensations from normal daily activities such as putting on a shirt or contact with a cool gentle breeze. If untreated, postherpetic neuralgia can adversely affect a patient's quality of life. Patients frequently fail to obtain complete pain relief with existing treatments or develop troublesome side effects."

Topical lidocaine patch (Lidoderm(R)), gabapentin (Neurontin(R)) and pregabalin (Lyrica(R)) are the only approved treatments for postherpetic neuralgia. Tramadol's pain relieving effects are due to multiple mechanisms of action, including serotonin and norepinephrine reuptake inhibition and opioid receptor activation. The current consensus is that multimodal analgesic therapy may be necessary to exploit the benefits of drugs with different mechanisms of action.

Najib Babul, PharmD, Chief Executive Officer of TheraQuest stated "New, long-acting formulations of tramadol in development are designed to gradually release their much larger tramadol content over a 24-hour period. TQ-1017 was engineered from the outset as a secure-release formulation of once-daily tramadol. It cannot be easily crushed for inhalation or to obtain rapid euphoria from high blood levels when swallowed. It is also difficult to extract tramadol from our once-daily formulation using common solvents, including alcohol. TheraQuest believes that these features may provide a greater margin of safety in the event of intentional or inadvertent attempts to defeat the timed release mechanism."

Babul adds, "We are particularly pleased to have been granted a second Orphan Drug Designation for tramadol for an important neuropathic pain indication. Orphan status affords us seven years of market exclusivity, 50% R&D Tax Credits, exemption from FDA Prescription Drug User Fee and access to research grants from the Office of Orphan Products Development."

Source: TheraQuest Biosciences

Cellumen, Inc., the systems cell biology company, and RheoGene Inc. announced that they have entered into a nonexclusive commercial licensing agreement under which Cellumen will use RheoGene's RheoSwitch® inducible gene regulation technology and RheoPlex™ multigene regulation technology to develop systems cell biology screening products including discovery collaborations, advanced reagents for High Content Screening (HCS) and stable cell lines.

Cellumen will offer these products to its pharmaceutical and biotechnology company customers.
The companies will also collaborate on the development and validation of mammalian cell lines to be used in Cellumen's proprietary systems cell biology profiling assays. Cellumen will provide expertise in molecular cell biology, High Content Screening and development of advanced reagents for cell analysis. RheoGene will contribute expertise in RheoSwitch® and RheoPlex™ system optimization, gene expression and development of stable cell lines.

Cellumen is creating new classes of reagents that "measure and manipulate" cell constituents used in multiplexed assays to yield a systems cell biology profile for drug discovery. The combined technologies will enable customers to manipulate the expression levels of one or two regulated cellular components including biosensor reporter molecules, functional proteins and siRNAs for both coding and noncoding RNAs. HCS profiling assays will be run on Cellumen's platforms. This emphasis on whole cell functions will allow better decisions to be made on what compounds to continue in the pipeline.

"We are pleased to have established a licensing agreement and collaboration with RheoGene," stated D. Lansing Taylor, CEO of Cellumen. "The incorporation of the RheoGene technologies into our advanced reagents for systems cell biology profiling will enhance our ability to deliver our 'measure and manipulate' approach to our customers. This approach will significantly increase the functional information on the impact of compounds on specific targets and cell functions."

"This opportunity to work with Cellumen is another excellent example of high value applications for our RheoSwitch® and RheoPlex™ technologies, that we will now extend into systems cell biology," said Thomas Tillett, CEO of RheoGene. "We will also collaborate with Cellumen on several projects that integrate our respective expertise."

Source: RheoGene