“Complete Response” Letters

FDA stopped issuing “approvable” and “not approvable” letters in favor of “complete response” letters on Aug. 11, 2008. The following chart lists “complete response” actions that were recently announced, as well as still-pending “approvable” and “not approvable” actions.
Product/Sponsor		Indication	Effective Date
Recently Announced “Complete Responses”
Intermezzo Zolpidem tartrate, sublingual lozenge Transcept Pharmaceuticals/Purdue Pharmaceutical Products		Low-dose sublingual formulation of zolpidem ( Ambien ) using Transcept’s Bimucoral technology for use as needed to treat insomnia when a middle of the night awakening is followed by difficulty returning to sleep	Announced 7/14/2011 (FDA asked for further investigation of next-day driving impairment, and questioned the adequacy of the Digit Symbol Substitution Test that the sponsor has used to evaluate next-day residual effects to assess driving ability; FDA suggested studying the contribution of body weight and demographics to morning-after blood levels, developing strategies to decrease next-morning zolpidem levels, and then, after implementing risk mitigation strategies, demonstrate that next-morning blood levels do not present an unacceptable risk of impairment, which may include another driving study)
Remoxy Oxycodone, controlled-release^a King Pharmaceuticals (Pfizer)/ Pain Therapeutics		Abuse-resistant long-acting oral formulation of the opioid for twice-daily treatment of moderate to severe pain requiring continuous opioid use for an extended period of time, using Durect Corporation’s Oradur technology to produce a tamper-resistant, high-viscosity liquid formulation in a hard gelatin capsule	Announced 6/24/2011 (A manufacturing issue is believed to be central to the CRL; previously received CRL 12/2008)
Pending “Complete Responses”
Acetadote Acetylcysteine^a Cumberland Pharmaceuticals		New indication for the acetaminophen overdose treatment for use in patients with non-acetaminophen-induced acute liver failure	Announced 12/22/2010 (FDA noted that while transplant-free survival was numerically higher in some coma patients, evidence was insufficient for increasing survival in all patients with acute liver failure)
Afrezza Insulin monomer human [rDNA origin] Mannkind		Ultra rapid-acting inhalation powder formulation of prandial insulin for treatment of adults with type 1 or type 2 diabetes for control of hyperglycemia	1/18/2011 (FDA’s main concern is the adequacy of the data bridging the MedTone inhaler used in Phase III and the Dreamboat device MannKind plans to commercialize, and called for two clinical studies of the new inhaler, one of which must have an arm that allows for head-to-head comparison of the devices; FDA also asked for more information on Dreamboat performance characteristics, usage, handling, shipment and storage, and information on user training and device labeling and packaging, as well as an Afrezza safety update)
Alogliptin^b Takeda		Dipeptidyl peptidase-4 inhibitor for once-daily treatment of type 2 diabetes as monotherapy and as an add-on to other antidiabetic medications	Announced 6/27/2009 (Additional studies expected to delay launch until 2012 or later; FDA had found the data insufficient to meet statistical requirements of cardiovascular risk guidance for type 2 diabetes drugs)
Alogliptin/pioglitazone^a Takeda		Fixed-dose combination of the DPP-4 inhibitor and the thiazolidinedione Actos to improve blood glucose control for treatment of type 2 diabetes in adults	9/2/2009 (Letter requests cardiovascular safety study that meets 12/2008 guidance on CV risk and antidiabetics)
Ampligen Rintatolimod^b (formerly known as PolyI:polyC12U) Hemispherx Biopharma		Toll-like receptor 3 agonist for treatment of chronic fatigue syndrome	11/25/2009 (Firm reports FDA found two of the four pivotal studies did not provide credible evidence of efficacy and recommended at least one additional trial, including multiple dose regimens and a QT interval study; letter also addressed non-clinical safety assessment, quality and manufacturing. Firm announced 11/29/2010 that it had requested an extension of up to 12 months to respond to CRL issues while it explores new data on the interrelationship of the retrovirus XMRV and CFS)
Amyvid Florbetapir F 18^b Lilly (formerly Avid Radiopharmaceuticals)		Diagnostic agent that binds to amyloid plaque for use with positron emission tomography to detect beta-amyloid plaques in the brains of living patients as part of the diagnosis of Alzheimer’s disease	Announced 3/18/2011 (FDA focused on “the need to establish a reader training program for market implementation that helps to ensure reader accuracy and consistency of interpretations of existing Amyvid scans,” Lilly reported)
Aricept Donepezil, transdermal^a Eisai/Teikoku Pharma/Pfizer		New weekly transdermal patch formulation of the cholinesterase inhibitor for treatment of mild, moderate and severe Alzheimer’s disease	Announced 4/25/2011
Avastin Bevacizumab^a Genentech (Roche)		Anti-vascular endothelial growth factor monoclonal antibody for use in combination with docetaxel ( Taxotere ) for first-line treatment of women with metastatic HER2-negative breast cancer; sBLA based on the AVADO trial.	Announced 12/16/2010 (Genentech announced concurrently that FDA had started the process of withdrawing Avastin’s Subpart H approval of its approved first line breast cancer use, with paclitaxel)
Avastin Bevacizumab^a Genentech (Roche)		Anti-vascular endothelial growth factor monoclonal antibody for use in combination with either a taxane, anthracycline-based or capecitabine ( Xeloda ) chemotherapy for first-line treatment of women with advanced (metastatic) HER2-negative breast cancer; based on the RIBBON1 trial	Announced 12/16/2010 (Genentech announced concurrently that FDA had started the process of withdrawing Avastin’s Subpart H approval of its approved first line breast cancer use, with paclitaxel)
Avastin Bevacizumab^a Genentech (Roche)		Anti-vascular endothelial growth factor monoclonal antibody in combination with chemotherapy for second-line use in treatment of women with advanced (metastatic) HER2-negative breast cancer; based on the RIBBON2 trial	Announced 12/16/2010 (Genentech announced concurrently that FDA had started the process of withdrawing Avastin’s Subpart H approval of its approved first line breast cancer use, with paclitaxel)
Aveed (formerly Nebido ) Testosterone undeconate Endo		Long-acting oil-based depot injection formulation of testosterone for treatment of male hypogonadism	12/3/2009 (Second "complete response" letter requests further information on potential for rare but serious adverse events and states proposed REMS is insufficient)
Axanum Aspirin/esomeprazole^a AstraZeneca		Fixed-dose combination of low-dose acetylsalicylic acid and a proton pump inhibitor for prevention of cardio- and cerebrovascular events in patients requiring continuous low-dose ASA treatment and who are at risk for developing ASA-associated gastric and/or duodenal ulcers	Announced 6/1/2010
Bupropion (CPI-300) Cary Pharmaceuticals/ IntelGenx		New, higher strength of the antidepressant formulated with IntelGenx’s oral controlled release technology for treatment of major depressive disorder	Announced 2/8/2010 (FDA identified two main issues to be addressed: qualification of a commercial manufacturing site and a food effect, that, according to IntelGenx, has been seen in CPI-300 and other extended-release bupropion products)
Bydureon Exenatide, sustained-release inj.^a (formerly Byetta LAR ) Amylin/Lilly/Alkermes		Once-weekly subcutaneous injection formulation of the incretin mimetic ( Byetta ) using Alkermes’ long-acting delivery technology, for treatment of type 2 diabetes	Announced 10/19/2010 (FDA requested a thorough QT study with exenatide exposures higher than typical therapeutic levels; FDA also asked for results of the DURATION-5 study to evaluate efficacy and labeling of the commercial formulation)
Cinryze C1 esterase inhibitor (human)^a ViroPharma/Lev		New claim for the plasma-derived C1 esterase inhibitor for treatment of acute attacks of hereditary angioedema	Announced 6/4/2009 (Firm reports FDA has requested an additional clinical trial but says agency had no safety concerns)
Cladribine Merck Serono (Merck KGaA)		Oral tablet formulation of the drug, which may interfere with lymphocyte proliferation, to reduce relapses in people with relapsing forms of multiple sclerosis	Announced 3/2/2011 (FDA requested an improved understanding of safety risks and overall risk-benefit profile through additional analyses or additional studies) (Development discontinued 6/2011)
Clolar Clofarabine ^a Genzyme		New indication for the oncologic for first-line therapy of previously untreated adults 60 years and older with acute myeloid leukemia who have at least one unfavorable prognostic factor	Announced 10/6/2009 (FDA recommends a randomized, controlled clinical study be conducted; firm will meet with FDA to determine if ongoing study will meet that requirement)
Comfyde Carisbamate^b Johnson & Johnson (Ortho-McNeil-Janssen Pharmaceuticals)		Anti-epileptic drug for adjunctive treatment of partial onset seizures in patients 16 years of age and older	Announced 8/21/2009
Contrave Naltrexone sustained-release/bupropion sustained-release Takeda/Orexigen		Fixed-dose combination of sustained-release formulations of naltrexone and bupropion for treatment of obesity	1/31/2011 (FDA is concerned about the drug’s cardiovascular safety when used long-term in overweight and obese patients and requested a randomized, double-blind, placebo-controlled trial of sufficient size and duration to assess if the risk of major adverse CV events affects the benefit-risk profile) Orexigen announced 6/3/2011 that it was discontinuing Contrave development in the U.S. and plans to appeal under FDA’s Formal Dispute Resolution process
CorVue Binodenoson^b King		Selective adenosine A2A receptor agonist for use as a cardiac pharmacologic stress SPECT imaging agent as an adjunct to non-invasive myocardial perfusion imaging tests to detect perfusion abnormalities in patients with or at risk for coronary artery disease who are unable to perform a cardiac exercise stress test	Announced 10/21/2009
Doxil Doxorubicin liposomal inj.^a Johnson & Johnson (Centocor Ortho Biotech)		New indication for the liposome-encapsulated chemotherapeutic for use in combination with Taxotere (docetaxel) for treatment of advanced breast cancer patients who have relapsed following prior anthracycline therapy	Announced 9/10/2009
Erbitux Cetuximab ^a ImClone (Lilly)/Bristol-Myers Squibb		New indication for the anti-EGFR monoclonal antibody for first-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based chemotherapy	Announced 3/2/2009 (FDA requests an additional pharmacokinetic study to confirm the comparability of clinical supplies used in the overseas EXTREME trial by Merck KGaA and Erbitux marketed in the U.S.; the same issue prompted the sponsors to withdraw an sBLA for advanced NSCLC 1/2009)
Esbriet Pirfenidone^b InterMune		Dual inhibitor of TGF-beta synthesis and TNG-alpha synthesis as an anti-fibrotic and anti-inflammatory agent to reduce declines in lung function in patients with idiopathic pulmonary fibrosis	5/4/2010 (FDA requested an additional efficacy trial, which, the agency suggested, could be another study using FVC as an endpoint or one using a mortality indicator.)
Fablyn Lasofoxifene tartrate^b Pfizer/Ligand		Selective estrogen receptor modulator for treatment of postmenopausal osteoporosis	Announced 1/16/2009 Pfizer withdrew NDA and is exploring strategic options as of 4/2011
Fentora Fentanyl, buccal tab. ^a Cephalon		New indication for the buccal tablet formulation of the opioid for management of breakthrough pain in opioid tolerant patients with chronic pain conditions	9/13/2008
Flutiform Fluticasone propionate/formoterol fumarate Skyepharma		Fixed-dose combination of the inhaled corticosteroid fluticasone and the long-acting beta agonist formoterol with hydrofluoroalkane propellant for metered dose inhaler use for maintenance treatment of asthma in patients 12 years of age and older	1/2010 ("Complete response" letter and subsequent meeting with FDA 6/2010 indicate "significant additional clinical work" is needed, including additional dose-ranging data. Skyepharma is determining if a "viable way forward" exists in the U.S.; Abbott returned U.S. marketing rights 8/2010)
Genasense Oblimersen Genta		Bcl-2 inhibitor in combination with chemotherapy for treatment of patients with relapsed or refractory chronic lymphocytic leukemia	Announced 12/2/2008 (In response to Genta’s 12/2008 appeal under FDA’s dispute resolution process, FDA determined available data to be inadequate to support approval and requested an additional trial, Genta announced 3/6/2009)
Gencaro Bucindolol HCl^b ARCA biopharma		Beta blocker and mild vasodilator for treatment of chronic heart failure in patients with a specific, common genetic variation	Announced 6/1/2009 (FDA requests additional clinical efficacy trial, as well as additional clinical pharmacology studies and non-clinical studies to further characterize metabolites. Firm notes amendments submitted 5/2009 were not reviewed prior to the action letter; amendments deal with comparative effectiveness, clinical pharmacology, pharmacogenetics and toxicology/metabolism and may be referenced in the response.)
Giazo Balsalazide^,1.1 g tab.^a Salix		New higher-strength tablet formulation of the 5-ASA prodrug balsalazide (marketed by Salix as Colazol 750 mg capsules), dosed as three tablets twice daily as opposed to Colazol's three capsules thrice-daily, for treatment of mild-to-moderate active ulcerative colitis in patients 18 years and older	4/27/2010 (FDA raised concerns about deficiencies at a contract manufacturing facility. Previously "approvable" 5/16/2008; FDA requested a new trial. Salix believed its NDA was sufficient and responded 6/2008 without a new trial; FDA issued a "complete response" 12/22/2008. Based on discussion with FDA, Salix reworked existing trial data and filed a response 10/2009.)
Girosa Flibanserin^b Boehringer Ingelheim		Non-hormonal agent that acts as a serotonin 5-HT1A receptor agonist and a 5-HT2A receptor antagonist for treatment of hypoactive sexual desire disorder accompanied by substantial distress in premenopausal women	Late 8/2010 (Sponsor announced 10/8/2010 that it was discontinuing development following the action letter due to "the complexity and extent of further questions that would need to be addressed")
Granisetron (APF530)^a A.P. Pharma		Long-acting formulation of granisetron utilizing the company’s proprietary Biochronomer delivery system for the prevention of acute and delayed-onset chemotherapy-induced nausea and vomiting	Announced 3/19/2010 (FDA expressed concerns regarding the two-syringe administration system. FDA also requires resolution of manufacturing deficiencies identified during inspection and requested a change to terminal sterilization with gamma irradiation. No new efficacy studies are requested, but FDA asked for re-analysis of select Phase III data as well as two new bioavailability and metabolism studies and a thorough QT study.)
Hydrocodone controlled-release/acetaminophen ^a Abbott		Controlled-release formulation of hydrocodone with activity over 12 hours compared with four-to-six hour dosing for immediate-release hydrocodone ( Vicodin )/APAP products, for treatment of pain	Announced 10/20/2008
Iclaprim^b, I.V. Arpida		Synthetic diamino-pyrimidine antibiotic for treatment of complicated skin and skin structure infections, including methicillin-resistance S. aureus	Announced 1/19/2009 (FDA requested an additional clinical study or studies showing non-inferiority to an approved comparator)
Iluvien Fluocinolone acetonide, intravitreal insert^a Alimera Sciences/pSivida		Extended-release intravitreal insert formulation of the corticosteroid that delivers sub-microgram levels of drug for up to 36 months for treatment of diabetic macular edema	Announced 12/23/2010 (FDA found 24 month data in NDA insufficient and asks for analysis of third year of FAME trial; letter also cites manufacturing, packaging and sterilization issues) NDA resubmitted 5/12/2011
Imagify Perflubutane polymer microspheres, inj. suspension^b Acusphere		Ultrasound imaging agent to assess myocardial perfusion for the detection of coronary artery disease (amended to limit use to subsets of patients undergoing pharmacologic stress techniques)	Announced 3/11/2009 (FDA said additional clinical work would be required for the broad CAD indication; will discuss alternatives with sponsor, which had submitted a limited indication 2/2009)
Linjeta Modified recombinant human insulin (formerly VIAject ) Biodel		Proprietary injectable formulation of recombinant human insulin that allows insulin to disassociate from a hexameric form to a monomeric form, thus promoting a more rapid delivery of insulin to the blood than currently marketed rapid-acting insulin analogs for treatment of diabetes	Announced 11/1/2010 (FDA pointed to numerous deficient areas in the NDA, including clinical trial, statistical analysis and manufacturing issues; FDA requested two new Phase III trials, one each in type 1 and type 2 diabetes)
Lorqess Lorcaserin^b Arena/Eisai		First of a new class of selective serotonin 2C receptor agonists for weight management, including weight loss and maintenance of weight loss, in obese and significantly overweight patients	10/23/2010 (FDA requested further investigation of tumor findings in rats, noting that, if teratogenicity concerns cannot be alleviated with non-clinical data, additional clinical studies may be required; FDA also called weight loss efficacy marginal in non-diabetic patients and requested the final study report from the BLOOM-DM trial in obese type 2 diabetes patients)
Luveniq Voclosporin^b Lux Biosciences/ Isotechnika		Oral formulation of the next-generation calcineurin inhibitor for treatment of noninfectious uveitis involving the intermediate or posterior segments of the eye	Announced 8/4/2010 (FDA recommended an additional trial be conducted)
MenHibrix Vaccine, H. influenzae type b/ meningococcus C and Y GlaxoSmithKline		Combination vaccine for immunization of infants and toddlers against meningococcal serogroups C and Y and Haemophilus influenzae type b diseases at two, four, six and 12-15 months of age	6/11/2010 Submission of additional information in response to the CRL announced 4/15/2011
Naproxcinod^b NicOx		Nitric-oxide donating form of naproxen as the first of a new class of anti-inflammatory agents, cyclooxygenase-inhibiting nitric oxide donators, for treatment of symptoms of osteoarthritis	Announced 7/22/2010 (FDA recommended one or more long-term controlled studies to assess cardiovascular and gastrointestinal safety, as well as additional studies to demonstrate a clinically meaningful therapeutic benefit attributable to the nitric oxide donation) (NicOx plans to appeal the CRL under FDA’s Formal Dispute Resolution process in Q1 2011)
Neupro Rotigotine, transdermal patch^a UCB		New indications for the transdermal patch for treatment of advanced Parkinson’s disease and moderate to severe primary restless legs syndrome	Announced 4/23/2010 (While FDA agreed that UCB's 6/2009 sNDA proposal for new refrigerated storage conditions could alleviate the crystal formation problem that prompted the 3/2008 Neupro withdrawal, the agency recommended a definitive resolution of the crystallization problem by reformulating the product. A previous action letter of 12/15/2008 also addressed drug crystal formation. UCB says it is working on a room-temperature stable, improved formulation.)
Neutroval Granulocyte colony-stimulating factor (Marketed in the EU as TevaGrastim ) Teva		Granulocyte colony-stimulating factor for the reduction in the duration of severe neutropenia and the incidence of febrile neutropenia in patients treated with established myelosuppressive chemotherapy for cancer; developed as a biosimilar version of Amgen's Neupogen (filgrastim)	Announced 9/30/2010 (Sponsor reports that the letter requests several items that it is reviewing, but asserts that no additional pre-marketing clinical trials are needed)
Nexium Esomeprazole^a AstraZeneca		New claim for the proton pump inhibitor for reduction in risk of low-dose aspirin-associated peptic ulcers	Announced 6/1/2010
Nucynta ER Tapentadol, extended-release^a Johnson & Johnson		Extended release formulation of the dual mu-opioid/norepinephrine reuptake inhibitor for management of moderate to severe chronic pain in patients age 18 and older	Announced 10/4/2010 (FDA requested data on conversion of the ER formulation used in the trial program to a different ER formulation designed to increase mechanical resistance to breaking or crushing)
Nuvigil Armodafinil^a Cephalon		New indication for the wakefulness agent for improved wakefulness in patients with excessive sleepiness associated with jet lag disorder resulting from eastbound travel	Announced 12/27/2010 (FDA reiterated concerns from 3/29/2010 action letter, like questioning the robustness of one of the two primary endpoints, the Patient Global Impression of Severity) (Cephalon will not pursue development further)
Omapro Omacetaxine^b ChemGenex		Cetaxine compound for treatment of patients with chronic myeloid leukemia who have failed treatment with imatinib ( Gleevec ) and who have developed the Bcr-Abl T315I mutation	Announced 4/12/2010 (FDA echoed the advisory committee's recommendation to delay approval until a validated assay to determine which patients have the T315I mutation is available)
Onrigin (formerly Cloretazine ) Laromustine^b Vion		Alkylating agent for use as a single agent for remission induction treatment for patients 60 years of age or older with de novo poor-risk acute myeloid leukemia	Announced 12/14/2009 (FDA has requested a randomized clinical trial to support the indication, but Vion says it does not have the funds for another clinical trial and is exploring options, including liquidation)
Opana ER Oxymorphone, extended-release^a Endo Pharmaceuticals/ Grunenthal		Crush-resistant extended-release formulation of the opioid for treatment of moderate-to-severe pain in patients requiring continuous around-the-clock opioid treatment for an extended period of time while deterring abuse, based on Grunenthal’s Tamper Resistant Formulation technology, which imposes mechanical stability using a combination of excipients	Announced 1/7/11 (Sponsor says no new clinical trials are required)
Oritavancin^b Targanta		Lipoglycopeptide antibiotic for treatment of complicated skin and skin structure infections, including cSSSI caused by methicillin-resistant Staphylococcus aureus	12/8/2008 (FDA requested an additional clinical trial enrolling sufficient number of patients with MRSA)
Pancrecarb Pancrelipase Digestive Care		Enteric-coated, bicarbonate-buffered pancreatic enzyme replacement therapy for treatment of exocrine pancreatic insufficiency	Announced 9/14/2009 (Company says no additional clinical trials were requested)
Pixuvri Pixantrone^b Cell Therapeutics		Major groove binder with an aza-anthracenedione structure that differentiates it from anthracyclines for treatment of relapsed or refractory, aggressive non-Hodgkin’s lymphoma	4/9/2010 (FDA advised the sponsor to conduct another trial pairing pixantrone with standard therapy. CTI announced it had filed an appeal under FDA's Formal Dispute Resolution process 12/3/2010.)
Prolia Denosumab^b Amgen		RANK ligand inhibitor for treatment and prevention of postmenopausal osteoporosis in women, and treatment and prevention of bone loss in patients undergoing hormone ablation for either prostate or breast cancer	Announced 10/19/2009 (Letter requests additional information on post-marketing surveillance program, updates safety information and a new clinical program for the prevention of PMO claim) (Class 2 response submitted in late 1/2010 for PMO treatment claim only; approved 6/1/2010)
Qnexa Phentermine/topiramate, controlled-release Vivus		Once-daily, controlled-release, fixed-dose combination of low dose phentermine and topiramate to address appetite and satiety in the treatment of obesity, including weight loss and maintenance of weight loss, in patients who are obese or overweight with co-morbidities	10/28/2010 (FDA requested a comprehensive assessment of teratogenic potential and evidence that elevation of heart rate seen with Qnexa does not increase risk for major adverse cardiovascular events)
Rabeprazole, extended-release^a Eisai		New extended-release 50 mg capsule formulation of the proton pump inhibitor (marketed in a delayed-release 20 mg tablet as Aciphex ) for the healing and maintenance of healing of erosive gastroesophageal reflux disease and for the treatment of symptomatic GERD	Announced 2/2/2011
Raxibacumab^b (formerly ABthrax ) Human Genome Sciences		Human monoclonal antibody that binds to protective antigen produced by Bacillus anthracis for the treatment of inhalation anthrax	Announced 11/16/2009 (Firm maintains that the letter "appears to be inconsistent" with FDA's animal rule for approval of new drugs when human efficacy studies are not feasible or ethical)
Restanza Cethromycin^b Advanced Life Sciences		Second-generation ketolide antibiotic for once-daily, oral treatment of mild-to-moderate community acquired pneumonia	7/31/2009 (FDA requested additional clinical data; company believes another trial in more severe CAP patients will likely be required) Advanced Life Sciences suspended operations 5/2011 due to lack of liquidity
Rezield Motavizumab^b MedImmune (AstraZeneca)		Monoclonal antibody that targets F-protein for prevention of serious respiratory syncytial virus disease in pediatric patients at high risk of RSV	Announced 8/30/2010 (FDA requested a new trial that supports a satisfactory risk/benefit profile in the indicated population) AstraZeneca announced withdrawal of BLA and discontinuation of RSV prophylaxis development 12/21/2010
Rituxan Rituximab ^a Genentech/Biogen Idec		New indication for the anti-CD20 antibody for treatment of earlier stage rheumatoid arthritis patients who have failed to respond to disease-modifying anti-rheumatic drugs, including methotrexate	Announced 10/19/2009 (Letter cites risk of progressive multifocal leukoencephalopathy with the biologic; firm will meet with FDA to discuss path forward)
Serdolect Sertindole^b Lundbeck		Atypical antipsychotic for treatment of schizophrenia	Announced 6/25/2009 (FDA requested additional data to buttress its understanding of the appropriate patient population)
Seroquel XR Quetiapine, extended-release^a AstraZeneca		New indication for the extended-release formulation of the atypical antipsychotic for treatment of generalized anxiety disorder in adults	Announced 2/27/2009 (AstraZeneca said 7/30/2009 that it was prioritizing the major depression sNDA over the GAD sNDA)
Sodium oxybate^a, oral solution (formerly Rekinla and JZP-6) Jazz		Sodium salt form of gamma-hydroxybutyrate that interacts with GABA(B) and GHB receptors in a 375 mg dose strength (as opposed to the 500 mg strength Jazz markets for cataplexy and narcolepsy as Xyrem ) for treatment of fibromyalgia	Announced 10/11/2010 (Additional clinical studies are needed; FDA asked sponsor to address appropriate patient population, methods for ensuring safe use and the proposed REMS, as well as the concentration and trade name)
Sollpura Liprotamase^b (formerly Altus' Trizytek , TheraCLEC ) Lilly (formerly Alnara)		Non-porcine, recombinant enzyme replacement therapy comprising amylase, lipase and protease to improve maldigestion in people with exocrine pancreatic insufficiency	Announced 4/15/2011 (FDA said another clinical trial would be necessary)
Stacatto loxapine Loxapine, inhaled Alexza		Antipsychotic approved in oral and injectable forms formulated for use in the company's Stacatto system, which vaporizes unformulated drug for deep lung inhalation, for the rapid treatment of agitation in patients with schizophrenia or bipolar disorder	10/8/2010 (FDA said NDA was not ready in present form. Primary clinical safety concern relates to FEV1 decreases in Phase I pulmonary safety studies; letter also questions suitability of stability studies. CDRH consulted on delivery system and added request for human factors testing and consideration of "worst case" manufacturing scenario)
Stedesa Eslicarbazepine^b Sepracor (Dainippon Sumitomo)/BIAL		Voltage-gated sodium channel blocker for adjunctive treatment of partial-onset seizures in adults with epilepsy	5/3/2010
Surfaxin Lucinactant^b Discovery Labs		Peptide-containing synthetic surfactant replacement therapy for prevention of respiratory distress syndrome in premature infants	4/17/2009 (FDA cited aspects of a biological activity test)
Symbicort Budesonide/formoterol fumarate ^a AstraZeneca		New pediatric indication for the inhaled corticosteroid/long-acting beta-2 agonist combination for long-term maintenance treatment of patients ages six to 11 with severe, persistent asthma	Announced 4/6/2009 (FDA said data was inadequate to establish dose and to establish how individual components contribute to the combination product in pediatrics)
Toremifene GTx		Selective estrogen receptor modulator, used at a higher dose than is approved for breast cancer (80 mg vs. 60 mg), for prevention of bone fractures in advanced prostate cancer patients taking androgen deprivation therapy	Announced 11/2/2009 (FDA requested a second Phase III trial and a clinical trial showing treatment does not have a detrimental effect on either time-to-disease progression or overall survival)
Uplyso ^b Taliglucerase alfa Pfizer/Protalix		Plant-cell expressed recombinant form of human glucocerebrosidase for the treatment of the lysosomal storage disorder Gaucher disease	2/25/2011 (FDA requested additional data from a switchover trial and a long-term extension trial, which were not available at the time of NDA submission; FDA also requested chemistry, manufacturing and controls information regarding testing specifications and assay validation)
Vibativ Telavancin^a Theravance/Astellas		New indication for the lipoglycopeptide antibiotic, for treatment of hospital-acquired (nosocomial) pneumonia caused by Gram-positive bacteria including methicillin-resistant S. aureus	11/27/2009 (FDA has requested submission of all available all-cause mortality data, company says, but did not request additional study; agency also requested further rationale for pooling data from two ATTAIN studies. Sponsor announced 1/27/2010 that FDA found its response to the CRL incomplete.)
Xifaxan Rifaximin 550 mg tabs.^a Salix Pharmaceuticals		New indication for the high-dose 550 mg tablet formulation of the gut-selective antibiotic for treatment of non-constipation irritable bowel syndrome and IBS-related bloating	3/7/2011 (FDA’s concerns relate primarily to what Salix calls a “newly expressed need” for retreatment information)
Yondelis Trabectedin^b Johnson & Johnson (Centocor Ortho Biotech)/PharmaMar		DNA minor groove binder in combination with Doxil (liposomal doxorubicin) for treatment of relapsed ovarian cancer	Announced 9/10/2009 (Letter requests overall survival data from ongoing pivotal trial and additional clinical pharmacology studies; FDA later said a new Phase III would be needed) J&J announced withdrawal of NDA 4/29/2011
Zalbin (formerly Albuferon )^b Albinterferon alfa-2b Human Genome Sciences/Novartis		Albumin-fusion biosimilar version of interferon for the treatment of chronic hepatitis C	Announced 10/5/2010 (Sponsors simultaneously announced they were choosing to discontinue development)
Zavesca Miglustat^a Actelion		New indication for the substrate reduction therapy for treatment of progressive neurological manifestations in adult and pediatric patients with Niemann-Pick type C disease	Announced 3/9/2010 (FDA requested additional preclinical and clinical information.)
Pending “Approvables”
Accretropin Recombinant human growth hormone ^a Cangene	Recombinant human growth hormone for treatment of growth failure in children with growth hormone deficiency and short stature associated with Turner syndrome		3/11/2007
Accutane Isotretinoin, capsule ^a (21-177) Roche	Once-daily formulation of the severe recalcitrant nodular acne treatment		10/27/2000
Akten Ophthalmic gel, 3.5% Akorn	Ocular anesthetic in a preservative-free, unit-dose topical gel formulation for use in any ocular procedure that requires a topical anesthetic agent		Announced 6/4/2008
Alvesco Ciclesonide Sanofi-Aventis/Altana	Inhaled corticosteroid for treatment of persistent asthma in patients four years of age and older		10/21/2004
Ariflo Cilomilast^b GlaxoSmithKline	Phosphodiesterase-4 inhibitor for treatment of chronic obstructive pulmonary disease in patients poorly responsive to albuterol		10/23/2003
Arixtra Fondaparinux ^a GlaxoSmithKline	Synthetic factor Xa inhibitor for use in patients with acute coronary syndromes		2/1/2007
Arxxant Ruboxistaurin ^b Lilly	Oral protein kinase C-beta inhibitor for treatment of diabetic retinopathy		8/17/2006
Bonefos Clodronate^b Berlex	Oral bisphosphonate for use as adjuvant treatment for reducing occurrence of bone metastases in stage II/III breast cancer		1/6/2005
Byetta Exenatide ^a Lilly/Amylin	Incretin mimetic for use as monotherapy in type 2 diabetes; simultaneously approved for adjunctive therapy		4/28/2005
CIP-Isotretinoin Cipher	Formulation of the retinoid for treatment of severe recalcitrant nodular acne unresponsive to conventional therapy, including systemic antibiotics		Announced 4/27/2007 (Also “approvable” 5/1/2006)
Combigan Brimonidine tartrate 0.2% & timolol maleate 0.5% ophthalmic solution^a Allergan	Combination of firm’s brimonidine product Alphagan with timolol for reduction of elevated intraocular pressure in patients with glaucoma or ocular hypertension who require adjunctive or replacement therapy due to inadequately controlled IOP		Announced 12/22/2006
Concerta Methylphenidate^a McNeil	New patient population, allowing use in adolescents with attention deficit/hyperactivity disorder, and new 72 mg dosing regimen		3/4/2004
Efaproxyn Efaproxiral^b (RSR-13) Allos	Radiation sensitizer for use as an adjunct to whole brain radiation therapy for the treatment of brain metastases from breast cancer		5/27/2004 (FDA requested results from ongoing ENRICH study; trial completed enrollment 8/2006)
Emend Fosaprepitant dimeglumine, inj. ^a Merck	Injectable formulation for treatment of chemotherapy-induced nausea and vomiting		Announced 5/14/2007 (Firm cites manufacturing validation and stability data)
Extravan Travoprost 0.004% & timolol 0.5% ^a Alcon	Fixed combination of firm’s prostaglandin analog travoprost ( Travatan ) and the beta blocker timolol for the treatment of glaucoma		Announced 9/17/2004
Fuzeon Enfuvirtide^a Roche/Trimeris	New claim for use with needle-free injector		Announced 11/23/2005 (Letter requests additional information from supporting trial; firms plan resubmission in H1 2007)
Galvus Vildagliptin^b Novartis	DPP-4 inhibitor for treatment of type 2 diabetes		2/23/2007
Hemopure Hemoglobin glutamer, bovine (HBOC-201) Biopure	Oxygen therapeutic delivered intravenously for treatment of signs and symptoms of acute anemia in adults undergoing orthopedic surgery, and to eliminate, delay or reduce the need for red blood cells in these patients		7/30/2003 (Firm has submitted proposed protocols for three requested preclinical studies)
Indiplon, immediate-release capsule^b Neurocrine	Non-benzodiazepine GABA-A receptor agonist for treatment of insomnia in adult and elderly patients		12/12/2007 (Second approvable letter requested three additional studies: clinical safety and efficacy studies in the elderly and a preclinical pregnancy study. Complete response announced 6/14/2007 to the first approvable letter of 5/15/2006)
Indiplon, modified-release tab.^a Neurocrine	Non-benzodiazepine GABA-A receptor agonist for treatment of insomnia in adult and elderly patients		5/15/2006
Intal HFA Cromolyn^a, nebulizer solution (20-957) King (acquired from Aventis)	Non-CFC formulation of the asthma therapy		Announced 10/30/2003; earlier letter issued 5/1999
Kynapid Vernakalant^b Astellas/Cardiome	Intravenous anti-arrhythmic for conversion of acute atrial fibrillation to sinus rhythm		8/8/2008 (FDA seeks data regarding previously identified events in a subset of patients)
Lercanidipine^b (21-377) Forest	Calcium channel blocker for treatment of hypertension		8/1/2002 (FDA asked for further clinical studies; as of 1/2006, firm says it has not yet responded and may evaluate modified release formulations)
Livial Tibolone^b Organon	Selective tissue estrogenic activity regulator (STEAR) for treatment of vasomotor symptoms, vulvar and vaginal atrophy and prevention of osteoporosis		6/1/2006 (Firm is stopping all efforts to market agent in U.S.)
Luvox CR Fluvoxamine, controlled-release ^a Jazz Pharmaceuticals/Solvay	Extended-release formulation of the selective serotonin reuptake inhibitor for treatment of obsessive compulsive disorder and social anxiety disorder		Announced 12/21/2007 (Second approvable letter; requests clarification regarding chemistry, manufacturing and controls)
Mucinex with codeine Guaifenesin/dextromethorphan/codeine, tab. ^a Adams Respiratory Therapeutics	Additional use for extended-release combination formulation for prescription treatment of cough associated with the common cold, inhaled irritants and stable chronic bronchitis		Announced 10/29/2007 (FDA requested data on use with food)
Namenda Memantine^a Forest	New claim for use of the NMDA receptor antagonist for treatment of mild to moderate Alzheimer’s disease		Announced 7/25/2005
Nexium Esomeprazole^a AstraZeneca	New claim for use of the proton pump inhibitor in healing gastric ulcers associated with NSAID therapy		11/24/2004
Omnaris Ciclesonide ^a Altana	Claim for use of the corticosteroid in treating nasal symptoms associated with seasonal and perennial allergic rhinitis in children ages 2-11 years		10/23/2006 (sNDA submitted 11/21/2007 for seasonal allergic rhinitis in children ages 6-12 years was also approved 11/21/2007)
Oxyprim Oxypurinol Cardiome	Active metabolite of the xanthine oxidase inhibitor allopurinol for the treatment of allopurinol-intolerant hyperuricemia (gout)		6/23/2004
Paxil Paroxetine GlaxoSmithKline	Six-month pediatric exclusivity extension based on studies in obsessive compulsive disorder		10/2002
Photrex Rostaporfin Miravant	SnET2-photodynamic therapy for treatment of wet age-related macular degeneration with any classic component (includes predominantly and minimally classic as well as lesions with or without occult components)		9/30/2004 (Letter requests additional confirmatory clinical trial)
Preos Parathyroid hormone ^a NPS	Recombinant full-length human parathyroid hormone to stimulate bone growth for treatment of osteoporosis in postmenopausal women with or without a previous fracture, subcutaneous injection formulation		3/9/2006
Prestara (formerly Aslera ) Prasterone^b Genelabs (licensed to Watson)	Treatment of women with systemic lupus erythematosus to limit bone loss while on low-dose glucocorticoids		8/12/2002 (FDA requested confirmatory study, initiated by firm 1/2003)
Prolacria Diquafosol tetrasodium (INS365), 2% ophthalmic solution^b Allergan/Inspire (firms will co-market)	Ocular P2Y2 receptor stimulator that enhances secretion of water, salt, mucin and lipids for treatment of dry eye		Announced 12/2/2005 & 12/19/2003
Pulminiq Cyclosporine, nebulizer solution Chiron	Aerosolized cyclosporine to increase survival and prevention of chronic rejection in patients receiving allogeneic lung transplants, for use in combination with standard immunosuppressive therapy		7/14/2005 (Letter requests confirmatory clinical study)
Requip CR Ropinirole ^a GlaxoSmithKline	14-hour controlled-release version of the non-ergot dopamine agonist for the treatment of restless legs syndrome		Announced 8/10/2007
Risperdal Risperidone ^a Johnson & Johnson	Atypical antipsychotic for treatment of schizophrenia in children ages 13-17		Announced 6/21/07
Rufinamide^b Eisai	Triazole derivative for use as adjunctive therapy in Lennox-Gastaut syndrome in children 4 years and older; and as adjunctive therapy for partial-onset seizures with and without secondary generalization in adults and adolescents ages 12 and olderr		9/15/2006 (Approved for the Lennox-Gastaut syndrome indication 11/14/2008)
Saforis Glutamine MGI	Powder for oral suspension form of glutamine for prevention and treatment of oral mucositis in patients receiving mucotoxic therapy; uses firm’s proprietary UpTec delivery system		10/12/2006 (Letter requests additional trial to establish efficacy)
SPD465 Shire	Extended-release formulation of the triple-beaded mixed amphetamine salts for symptom control of attention deficit/hyperactivity disorder for adults; contains same active ingredient as firm’s Adderall		Announced 5/18/2007 (FDA is seeking clarification of additional data)
Tacrolimus (FK506), modified-release ^a (formerly Prograf MR ) Astellas	Once-daily formulation of the immunosuppressant for prophylaxis of organ rejection in kidney transplant patients		3/13/2008 (Previous “approvable” letter received 1/19/2007)
Tacrolimus (FK506), modified-release ^a (formerly Prograf MR ) Astellas	Once-daily, modified-release formulation of firm’s immunosuppressant for prevention of organ transplant rejection in liver transplant patients		4/30/2008 (Previously approvable 1/19/2007)
Thelin Sitaxsentan ^b Encysive (acquired by Pfizer 6/10/2008)	Endothelin receptor antagonist for the treatment of pulmonary hypertension		Announced 6/15/2007 (Third “approvable” letter; FDA recommends additional clinical trial) Pfizer discontinued all clinical studies of Thelin for PAH and withdrew the drug from markets where it was approved 12/2010
Topamax Topiramate ^a Ortho-McNeil	New indication for use as monotherapy in newly diagnosed epileptic adults and children six years and older		11/26/2003
Tygacil Tigecycline^a Wyeth	New indication for the glycylcycline antibiotic for treatment of community-acquired pneumonia		Announced 5/29/2008
Valstar Valrubicin Indevus	Sterile solution of valrubicin for intravesical instillation therapy of bacillus Calmette-Guerin-refractory carcinoma in situ of the urinary bladder		Announced 8/17/2007 (FDA cites need for CMC clarification)
Viviant Bazedoxifene^b Wyeth	Selective estrogen receptor modulator for treatment of postmenopausal osteoporosis		5/21/2008
Viviant Bazedoxifene ^b Wyeth	Second-generation selective estrogen receptor modulator for prevention of postmenopausal osteoporosis		Announced 12/24/2007 (Second approvable letter; requested further data on stroke and venous thromboembolism, also raises data collection and reporting issues. First approvable letter issued 4/23/2007)
Zentase (tradename under dispute with Ferring; formerly EUR-1008) Pancrealipase Eurand	Highly stable formulation of eight porcine-derived pancreatic enzymes and coenzymes and cofactors for treatment of exocrine pancreatic insufficiency		Announced 6/18/2008
Zortress Everolimus (formerly Certican ) Novartis	Rapamycin derivative macrolide immunosuppressant/mTOR inhibitor (approved with different dosing for renal cancer as Afinitor ) for use with cyclosporine to prevent acute rejection episodes following heart and kidney transplantation		8/27/2004 & 10/20/2003 (Novartis has continued to study kidney transplant use but has not responded on the heart indication. The 2004 letter referenced Novartis' 2/27/2004 NDA amendment containing two open-label kidney transplant studies; FDA cited limited regulatory value of studies lacking a control group. Novartis submitted a full response on 6/30/2009 with a new Phase III kidney transplant study) (Approved for kidney transplant patients 4/20/2010)
Pending “Complete Reviews”
Aranesp Darbepoetin alfa ^a Amgen	New claim for once every-two-week and maintenance once-monthly dosing regimens for chronic kidney disease patients with anemia not on dialysis		Announced 10/13/2006
Avastin Bevacizumab ^a Genentech	New claim for treatment of recurrent or metastatic breast cancer in combination with taxane chemotherapy for patients who have not previously received chemotherapy for metastatic breast cancer		Announced 9/11/2006
Doribax Doripenem, inj. ^a Johnson & Johnson	New indication for the carbapenem antibiotic for treatment of nosocomial pneumonia		8/19/2008
FluMist Influenza vaccine live ^a MedImmune	Refrigerator-stable formulation of the intranasal influenza vaccine		7/18/2006
Gardasil Quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine ^a Merck	Labeling expansion to include efficacy data showing cross-protection against additional cervical cancer-causing HPV types responsible for greater than 10 percent of cervical cancers, data on protection against additional gynecological cancers (vaginal and vulvar) and data on immune memory		Announced 6/25/2008 (FDA said that the data submitted do not support extending Gardasil’s indication to include non-vaccine HPV types) (Approved for prevention of vaginal and vulvar cancer caused by HPV types 16 and 18 in girls and women ages 9 to 26 on 9/12/2008)
Rebif Interferon beta-1a ^a Merck Serono	Human serum albumin-free and fetal bovine serum-free formulation of the relapsing multiple sclerosis therapy		Announced 2/7/2007
Pending “Not Approvables”
Advair Diskus 500/50 Fluticasone/salmeterol inhalation powder^a GlaxoSmithKline	Higher dosage form of the long-acting beta agonist bronchodilator for the treatment of chronic obstructive pulmonary disease		8/6/2007 (FDA asks for head-to-head data with firm’s 250/50 mcg strength
Altabax Retapamulin^b GlaxoSmithKline	Topical pleuromutilin for treatment of uncomplicated skin and skin structure infections due to susceptible strains of Staphylococcus aureus and Streptococcus pyogenes		4/20/2007 (FDA initially issued approvable decision 12/2006)
Altabax Retapamulin^b GlaxoSmithKline	Topical pleuromutilin for treatment of secondarily-infected dermatoses		Announced 12/22/2006
Angiomax Bivalirudin ^a The Medicines Company	New indication for the thrombin-specific antithrombotic for treatment of acute coronary syndromes initiated in the emergency setting		Announced 5/28/2008
Arcoxia Etoricoxib^b Merck	Follow-on to firm’s withdrawn COX-2 inhibitor Vioxx for treatment of osteoarthritis		4/27/2007
Bifeprunox^b Wyeth/Solvay	Atypical antipsychotic for the treatment of schizophrenia		Announced 8/10/2007 (Firms will pursue “maintenance” indication for stable adult patients with schizophrenia)
Bijuva Synthetic conjugated estrogens, A, cream^a Barr	Topical estrogen formulation for treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause		4/26/2005 (Letter requests additional clinical data)
Bridion Sugammadex^b Schering-Plough	Selective relaxant binding agent to reverse neuromuscular blockade induced by rocuronium and vecuronium as part of general anesthesia during surgical procedures		Announced 8/1/2008
Dapoxetine^b Johnson & Johnson	Selective serotonin reuptake inhibitor for prevention of premature ejaculation		10/26/2005
Emezine Prochlorperazine BioDelivery Sciences	Transmucosal formulation of the antiemetic for treatment of nausea and vomiting		2/28/2006
Firazyr Icatibant^b, inj. Shire (formerly Jerini)	Bradykinin blocker for treatment of hereditary angioedema		Announced 4/24/2008 (Sponsor full response submission announced 2/28/2011)
Gepirone ER,^b tab. Fabre-Kramer Pharmaceuticals	Serotonin receptor agonist for treatment of adults with major depressive disorder		Announced 11/2/2007 (Third approvable letter; firm cites efficacy concerns)
Injectafer Ferric carboxymaltose, I.V. ^a Daiichi Sankyo/Luitpold	Intravenous iron replacement product for iron deficiency anemia in postpartum patients and women with heavy uterine bleeding		Announced 3/12/2008 (FDA requested additional clinical trials to collect more information about mortality signal vs. oral iron; first “not approvable” letter in 6/2006 also cited mortality signal)
Istradefylline^b Kyowa	Adenosine A2A antagonist as an adjunct to carbidopa/levodopa to improve motor functioning in Parkinson’s disease patients with motor response complications		2/25/2008 (FDA questioned if efficacy findings support clinical utility, and requested summary of nonclinical mineralization findings and clinical pharmacology follow-up information)
Lexapro ^a Escitalopram Forest	New indication for use of the SSRI in panic disorder		Announced 3/1/2005 (Also not approvable 2/25/2004)
Lexapro ^a Escitalopram Forest	New indication for use of the SSRI in social anxiety disorder		3/25/2005 (Letter raises questions about single study center)
Loratadine/montelukast ^a Merck/Schering-Plough	Combination of Merck’s leukotriene antagonist Singulair and Schering-Plough’s Claritin for treatment of allergic rhinitis symptoms in patients who want relief from nasal congestion		4/25/2008
Marqibo Vincristine Ilex/Enzon	Liposomal-encapsulated vincristine for single-agent treatment of patients with relapsed aggressive non-Hodgkin’s lymphoma previously treated with at least two combination chemotherapy regimens		1/14/2005 (Letter recommends additional clinical studies with improved designs)
Mifamurtide^b IDM Pharma	Immunomodulator for the treatment of nonmetastatic osteosarcoma		Announced 8/27/2007 (Firm says FDA requested additional data from additional clinical trials)
Fablyn Lasofoxifene^b Pfizer/Ligand (formerly Oporia )	Next-generation selective estrogen receptor modulator for prevention of osteoporosis in postmenopausal women		Announced 9/13/2005 (Pfizer withdrew NDA and is exploring strategic options as of 4/2011)
Orapem Faropenem medoxomil^b Forest/Replidyne	Orally bioavailable ester prodrug of faropenem for treatment of acute bacterial sinusitis, community-acquired pneumonia, acute exacerbations of chronic bronchitis and uncomplicated skin and skin structure infections		10/20/2006
orBec Oral beclomethasone dipropionate, tab. ^a Dor Biopharma	New use for tablet formulation to treat acute gastrointestinal Graft-versus-Host disease		Announced 10/19/2007 (FDA requests additional clinical data)
Parecoxib^b Pfizer	Injectable pro-drug of firm’s withdrawn COX-2 inhibitor Bextra (valdecoxib)		Announced 9/20/2005 (Also not approvable in 2001)
Prexige Lumiracoxib ^b Novartis	COX-2 inhibitor for the treatment of osteoarthritic pain		Announced 9/27/2007 (Second “not approvable” letter; FDA requests additional studies, data on liver profile)
Prograf MR Tacrolimus ^a Astellas	Once-daily, modified-release formulation of firm’s immunosuppressant for prevention of organ transplant rejection in heart transplants		1/19/2007
Pulzium Tedisamil^b Solvay	Potassium channel blocking Class III anti-arrhythmic drug for treatment of recent onset atrial fibrillation or atrial flutter		1/18/2008
Risperdal Risperidone ^a Johnson & Johnson	New indication for treatment of psychosis in Alzheimer’s dementia		Announced 5/26/2005
Symlin Pramlintide ^a Amylin	Additional claim for the glucose metabolism regulator for treatment of type 2 diabetes in combination with basal insulin alone (without mealtime insulin)		Announced 10/1/2007 (FDA cites inadequate efficacy; firm says it plans to pursue the indication)
T-Pred Prednisolone acetate/tobramycin Ista	Topical, fixed-dose combination of the corticosteroid and aminoglycocide antibiotic for treatment of inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial ocular infections or a risk of bacterial infection exists		5/3/2007
Tredaptive (formerly Cordaptive ) Laropiprant ^b/niacin Merck	Combination of extended-release niacin and firm’s novel DP1 flushing pathway inhibitor, which selectively blocks the binding of the prostaglandin PGD2 to its DP1 receptor, for treatment of elevated LDL cholesterol, low HDL cholesterol and elevated triglyceride levels either alone or with a statin, as an adjunct to diet and exercise		4/28/2008
Vadova Carbidopa/levodopa Impax	Extended-release formulation of the Parkinson’s disease combination treatment		Announced 3/7/2006 (Letter cites chemistry deficiencies); second “not approvable” letter announced 1/30/2008, cites concerns about nomenclature and medication errors)
Valstar ^a Valrubicin Indevus	Sterile solution of valrubicin for intravesical instillation to treat bacillus Calmette-Guerin-refractory carcinoma in situ of the urinary bladder		Announced 12/19/2007 (Manufacturing facilities deficiencies cited for previously approvable sNDA to return Valstar to market. Drug was withdrawn in 2002 due to impurities in original formulation.)
Velac Clindamycin/tretinoin Connetics	Combination therapy for acne vulgaris		6/10/2005
Vitaros (formerly Alprox TD ) Alprostadil, cream NexMed/Warner Chilcott	Topical treatment of erectile dysfunction		Announced 7/22/2008 (Transgenic mouse carcinogenicity study is the major issue)
Xcytrin Motexafin gadolinium^b Pharmacyclics	Paramagnetic thioredoxin reductase inhibitor for treatment of non-small cell lung cancer with brain mestastases		Announced 12/21/2007
Xinlay Atrasentan^b Abbott	Selective endothelin-A receptor antagonist for treatment of metastatic, hormone-refractory prostate cancer		10/13/2005
Zarnestra Tipifarnib^b Johnson & Johnson	Farnesyl transferase inhibitor for treatment of newly diagnosed acute myeloid leukemia		Announced 6/30/2005 (Letter requests additional information on pivotal trial’s patient population)
Zimulti (formerly Acomplia ) Rimonabant ^b Sanofi-Aventis	Selective cannabinoid-1 receptor blocker for use in smoking cessation		2/17/2006
^a Submission is for a new use or new formulation of product that sponsor already markets ^b New molecular entity or combination product with NME as component