Tasimelteon

Vanda Presents Data From Tasimelteon Phase III Studies In Non-24-Hour Disorder

 WASHINGTON, June 5, 2013 /PRNewswire/ — Vanda Pharmaceuticals Inc. (Vanda) presented additional entrainment and patient-level clinical data at SLEEP 2013, the 27th Annual Meeting of Associated Professional Sleep Societies in Baltimore, from its SET (Safety and Efficacy of Tasimelteon) and RESET (Randomized-withdrawal study of the Efficacy and Safety of Tasimelteon to treat Non-24-Hour Disorder) Phase III studies of tasimelteon, a circadian regulator for the treatment of Non-24-Hour Disorder (Non-24) in totally blind individuals. Non-24 is a serious, rare and chronic circadian rhythm disorder that affects a majority of totally blind individuals who lack light perception and cannot entrain (synchronize) their master body clock to the 24-hour day. Currently there is no approved FDA treatment for Non-24.

In the SET study, tasimelteon achieved the primary endpoints of entrainment (synchronizing) of the melatonin (aMT6s) rhythm as compared to placebo and clinical response as measured by entrainment plus a score of greater than or equal to 3 on the Non-24 Clinical Response Scale (N24CRS). Tasimelteon also demonstrated significant improvement versus placebo across a number of sleep and wake parameters including measures of total sleep time, nap duration, and timing of sleep, as well as in the Clinical Global Impression of Change (CGI-C), an overall global functioning scale. In treated patients, daytime naps decreased by 46 minutes per day in the worst 25% of days in a cycle and nighttime sleep increased by 57 minutes per day during the worst 25% of nights in a cycle.

The RESET study demonstrated that continued treatment with 20mg of tasimelteon was required to maintain entrainment of melatonin and cortisol circadian rhythms in individuals with Non-24. Patients treated with tasimelteon maintained their clinical benefits while patients who received placebo showed significant deterioration in measures of nighttime sleep, daytime naps and timing of sleep. Furthermore, discontinuation of tasimelteon resulted in a rapid relapse of circadian entrainment and a return to misaligned circadian rhythms, reinforcing the importance of chronic therapy.

Study investigator, Steven W. Lockley, Ph.D., Associate Professor of Medicine, Division of Sleep Medicine, Brigham and Women’s Hospital, Harvard Medical School, commented, “the results clearly demonstrate that tasimelteon can entrain the circadian clock, and that continued treatment is necessary to maintain entrainment.”

About Tasimelteon: Tasimelteon is a circadian regulator in development for the treatment of Non-24. Tasimelteon is a dual melatonin receptor agonist (DMRA) with selective agonist activityat the MT1 and MT2 receptors.Tasimelteon’s ability to reset the master body clock in the suprachiasmatic nucleus (SCN) results in the entrainment of the body’s melatonin and cortisol rhythms with the 24-hour day-night cycle. The patent claiming tasimelteon as a new chemical entity extends through December 2022, assuming a 5-year extension to be granted under the Hatch-Waxman Act. Tasimelteon has been granted orphan drug designation for the treatment of Non-24 from both the U.S. and the European Union.

Fedratinib (SAR-302503)

Sanofi’s JAK2 Inhibitor Meets Primary Endpoint in Late-Stage Trial for Treatment of Myelofibrosis

Today, Sanofi announced that its JAK2 inhibitor met the primary endpoint in both dose groups during a Phase III study evaluating the drug for treatment of myelofibrosis.

The pivotal study, JAKARTA, evaluated once-daily, oral SAR302503 compared to placebo. The study consisted of 289 patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis, which were randomly assigned a 400mg dose of SAR302503, 500mg dose of SAR302503, or placebo for 24 weeks. The primary endpoint was the proportion of patients with a reduction in spleen volume ≥ 35 percent after 24 weeks of treatment. According to the company, the primary endpoint was met and full results will be presented at an upcoming medical congress.

“Patients with myelofibrosis in advanced stages are desperately ill and in need of treatments that will improve their outcomes. I am pleased with the results of JAKARTA and would like to thank the patients and the investigators in this trial,” Debasish Roychowdhury, MD, Senior Vice President and Head, Sanofi Oncology stated. “Since Sanofi’s acquisition of the molecule, SAR302503 has moved from Phase I to the completion of pivotal Phase III studies in less than three years, and now we are planning regulatory filings with authorities to make this medicine available for patients.”

Myelofibrosis (MF) is a rare, serious blood disease. MF is characterized by an abnormal blood cell production and fibrosis (scarring) within the bone marrow. Scarring of the bone marrow interferes with blood cell production, which causes the spleen and liver to produce and store extra blood cells, causing an enlarged spleen. For patients with intermediate-2 and high-risk patients, median survival is approximately two and a half years and for MF patients overall is approximately six years.

Source: Sanofi

Bedaquiline

Bedaquiline
Fast-track approval for treatment of tuberculosis
May 3, 2013

Bedaquiline (Sirturo) represents a new class of anti-TB drugs called diarylquinolines that have a novel mechanism of action to stop replication of TB. It has FDA approval for treatment of multi-drug resistant pulmonary TB. The drug has not been evaluated with extra-pulmonary TB affecting the CNS. Standard treatment involves a four-drug regimen with isoniazid, rifampin and pyrazinamide (PZA). A recent meta-analysis showed the percentage of patients dying from TB was 3% in non-HIV patients, 9.2% in HIV-infected patients and 30.9% in HIV-infected patients with multi-drug resistant TB. This drug achieved fast-track approval by the FDA due to risks associated with multi-drug resistant TB.
Recent clinical trials included patients with pulmonary TB and used the same dosing strategy (400 mg orally twice daily for two weeks followed by 200 mg three times per week). The clinical endpoint was the time to convert to a normal sputum culture (culture conversion), which indicates cessation of mycobacterium growth.
A phase 2 study assessed the mycobacterial activity and safety of using bedaquiline added to standard therapy. Adult patients with the presence of acid-fast bacilli in sputum that were resistant to isoniazid and rifampin were included. Patients with uncontrolled HIV were excluded.
This eight-week study was conducted in South Africa and was a double-blind, placebo-controlled study. The study group (n = 47) had a median age of 33 years, 74% were male and 87% were HIV-negative. The study drug significantly decreased the time to culture conversion (p = 0.003), and resulted in a greater proportion of patients who were culture negative (48% versus 9%). Strengths of the study were achieving a 97% medication adherence rate.
A two-year follow-up of these patients found 23 patients (48.9%) in both treatment arms had discontinued the study. At week 24, 81% in the bedaquiline group and 65.2% in the placebo group maintained culture conversion.
Bedaquiline is effective against mycobacterium isolates resistant to isoniazid, rifampin PZA and others.5 It acts by inhibiting a proton pump affecting the cellular enzyme, ATP synthase, which depletes the cell’s stores of ATP and ultimately decreases mycobacterium survival.5,6 It has bactericidal activity and a minimum inhibitory concentration that is similar or lower than current drugs.
Dosage, Costs, Pharmacokinetics
Bedaquiline is used in combination with at least three other drugs. The initial dose is 400 mg orally once daily for two weeks, followed by a maintenance dose of 200 mg orally three times per week for 22 weeks. The treatment continues for a total of 24 weeks. Maintenance doses should be scheduled on specific days (e.g., Monday-Wednesday-Friday) to promote adherence.
In patients who are non-adherent or fail therapy, use Directly Observed Therapy. The doses are available in 100 mg tablets, and should be taken with water and food. Patients should store their medications in the original container. Tablets stored in a medication organizer can break down due to exposure to light and moisture.
Bedaquiline has a long half-life for the active drug (164 days) and M2 metabolite (159 days).1,4,6 The metabolite is less active than the parent drug. The drug is slowly released from the peripheral tissues, which accounts for the persistent concentration in the blood. The maximum concentration is achieved six hours after taking a 400 mg dose.
The drug is highly protein-bound (99%). It is metabolized by the hepatic cytochrome P450 3A4 enzyme and is susceptible to drug interactions by this pathway. The drug should be used cautiously in patients with severe kidney dysfunction. The benefits should outweigh the risks if used with severe liver dysfunction.
Drug Interactions & Side Effects
Common side effects are headache and nausea. Patients also reported arthralgia, hemoptysis and rash. The FDA prescribing information warns about the potential for developing harmful ventricular arrhythmias (long QT syndrome). In follow-up studies, QT interval was prolonged but there were no readings higher than 500 msec.
The proportion of patients dying during one clinical study was greater in the bedaquiline group versus the placebo group. The reasons for this are unclear. Therefore, the boxed warning cautions to only select this drug for patients who are not candidates for other approved drugs. This underscores the need to closely monitor patients with frequent follow-ups. Some adverse effects identified in clinical studies were not found to be significantly different than the placebo-group and include non-cardiac chest pain and deafness.
Take a medication history and advise patients to stop any CYP3A4 inhibitors for 14 days before starting bedaquiline.1 Carefully select and monitor drug therapy to avoid interactions that may cause QT interval prolongation on the electrocardiogram.
Drugs that may have an additive effect on prolonging the QT interval include clofazimine (a drug for TB), tricyclic antidepressants, dofetilide and others. Drugs that inhibit CYP3A4 are macrolide (erythromycin, clarithromycin) and fluoroquinolone (levofloxacin) antibiotics, and ketaconazole (antifungal). Rifampin, a main-stay of therapy for TB, and others in the class (rifabutin, rifapentine) are hepatic enzyme inducers and may decrease levels of bedaquiline. If used in HIV co-infected patients, current literature should be evaluated to determine if new information is available on interactions with HIV drugs.
Frequent monitoring should include checking hepatic transaminases (AST, ALT, alkaline phosphatase), total bilirubin and uric acid (hyperuricemia). Check an electrocardiogram to measure QT intervals at baseline, weeks two, 12 and 24. Order and maintain electrolytes within normal limits (calcium, magnesium, potassium)

NX-1207

New Study Supports Favorable Sexual Function Profile For Nymox’s NX-1207 For Prostate Enlargement

 BY GlobeNewswire|04/16/13 – 10:32 AM EDT

HASBROUCK HEIGHTS, N.J., April 16, 2013 (GLOBE NEWSWIRE) — Nymox Pharmaceutical Corporation (Nasdaq:NYMX) reported today positive new study findings which have demonstrated that the Company’s NX-1207 Phase 3 treatment for benign prostatic hyperplasia (BPH or prostatic enlargement) has no detectable effect on key male structures involved in sexual function. This study has provided new data which offers further scientific support of highly selective sparing of prostatic nerves after NX-1207 treatment. In addition, over 1000 patients in clinical trials who have received Nymox’s NX-1207 have not shown any clinical sexual problems related to the drug. One of the several major problems with other existing prostate treatments is the predictable collateral damage to sexual organs which produces serious problems such as impotence, loss of libido, and retrograde ejaculation.

In other studies, intraprostatic NX-1207 has been shown to have no effects on adjacent key organs such as penis and testis, seminal vesicles, urethra and bladder. Male hormone levels are unaffected by NX-1207 treatment.

Surgical and other minimally invasive treatments for benign prostatic hyperplasia (BPH) are non-selective in their effects on the prostate. The end result is improved urinary function at the undesirable cost of lost sexual function. These treatments are known to cause long-term impairment or loss of sexual function in a significant percentage of treated patients.

Drugs that provide only minor improvement in urination frequently produce sexual problems. For example, 5-α-reductase inhibitors (5ARI) often lead to loss of libido, impotence, or male breast enlargement (gynecomastia). Alpha-blocker drugs frequently cause retrograde ejaculation (ejaculation into the bladder) or impotence.

NX-1207 is a novel patented drug developed by Nymox which is currently in Phase 3 trials for BPH and Phase 2 for localized prostate cancer. The drug has successfully completed a series of blinded controlled multi-center U.S. clinical trials where a single dose of NX-1207 has been found to produce on average symptomatic improvements about double that reported for currently approved BPH drugs without causing the sexual or cardiovascular side effects associated with those drugs. Follow-up studies have shown evidence of long lasting benefit with a significant proportion of men who received a single dose reporting maintained improvement in BPH symptoms without other treatments for up to 7½ years.

Fostamatinib

AstraZeneca Reports Mixed Phase III Results For Rheumatoid Arthritis Candidate

4/5/2013 3:39 AM ET

Anglo-Swedish drug maker AstraZeneca Plc, on Friday said that a phase III study to assess the efficacy and safety of its drug candidate Fostamatinib for rheumatoid arthritis met one primary endpoint, while it failed in its second primary goal.

The trial, dubbed OSKIRA-1, had two primary endpoints namely, assessing signs and symptoms of rheumatoid arthritis as measured by ACR20 response rates, and an X-ray endpoint known as mTSS (modified Total Sharp Score). While Fostamatinib achieved a statistically significant improvement in ACR20 response rate compared to placebo in the trial, it failed to achieve statistical significance in mTSS.

The company added that the safety and tolerability findings for Fostamatinib observed in the OSKIRA-1 study were generally consistent with those previously reported for the TASKi Phase II program. In the study, the most commonly reported adverse events were typical of those seen in earlier studies, including hypertension, diarrhoea, nausea, headache and nasopharyngitis or common cold.

RA is a systemic autoimmune disease in which the immune system attacks the joints, causing pain, swelling to the surrounding tissue and damage to the cartilage and bone. If not adequately treated, RA can destroy cartilage and bone within joints, leading to serious disability. Clinical-stage drug development company Rigel Pharmaceuticals, Inc. developed the compound, and in February 2010, AstraZeneca signed a worldwide license agreement to develop and commercialise fostamatinib, previously referred to as R788.
Briggs Morrison, Executive Vice President of Global Medicines Development and Chief Medical Officer, said, “We will await the results of the remaining Phase III studies, OSKIRA-2 and OSKIRA-3, to further evaluate and characterise the profile of fostamatinib as a potential treatment for rheumatoid arthritis.”The ongoing OSKIRA program has been designed to investigate fostamatinib as a potential new oral treatment option for RA and an alternative to injectable therapies for patients with an inadequate response to conventional Disease Modifying Anti-Rheumatic Drugs, including methotrexate and those with an inadequate response to TNF-a antagonists.

The OSKIRA-2 and OSKIRA-3 results are expected later in the second quarter of 2013.

Lomitapide (Juxtapid)

Lomitapide (Juxtapid)

FDA approved  on 21 December 2012

Lomitapide is a cholesterol-lowering medication. It reduces blood levels of “bad” cholesterol, such as low-density lipoprotein (LDL) or non-high-density liproprotein (non-HDL), as well as a protein that carries bad cholesterol in the blood. Lomitapide is used together with a low-fat diet and other treatments to lower total cholesterol in people with homozygous familial hypercholesterolemia (an inherited type of high cholesterol).

It is not known whether lomitapide will lower your risk of heart disease.

What is the most important information I should know about lomitapide?

Do not use lomitapide if you are pregnant. Some medicines can interact with lomitapide and should not be used at the same time. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with lomitapide.

Grapefruit and grapefruit juice may interact with lomitapide and lead to unwanted side effects. Do not drink grapefruit juice while taking lomitapide.

Stop using lomitapide and call your doctor at once if you have nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

What should I discuss with my healthcare provider before taking lomitapide?

Lomitapide is available only under a special program called the Juxtapid REMS Program. You must be registered in the program and understand the risks and benefits of taking this medication. You should not use lomitapide if you are allergic to it, if you have severe liver disease, or if you are pregnant.

Some medicines can interact with lomitapide and should not be used at the same time. Your doctor may need to change your treatment plan if you use any of the following drugs:

• aprepitant, cimetidine, conivaptan, cyclosporine, haloperidol, imatinib, isoniazid.
• To make sure lomitapide is safe for you, tell your doctor if you have:

• an antibiotic–ciprofloxacin, clarithromycin, doxycycline, erythromycin, metronidazole, norfloxacin, telithromycin, tetracycline;
• an antidepressant–desipramine, nefazodone, sertraline;
• antifungal medication–clotrimazole, fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole;
• the hepatitis C medications boceprevir or telaprevir;
• heart or blood pressure medicine–amiodarone, diltiazem, dronedarone, lidocaine, nicardipine, quinidine, verapamil; or
• HIV or AIDS medicine–atazanavir, darunavir when given with ritonavir, delavirdine, efavirenz, fosamprenavir, indinavir, nelfinavir, saquinavir.

• liver disease;
• kidney disease (or if you are on dialysis); or
• hereditary galactose intolerance, severe lactase deficiency, or glucose galactose malabsorption.

How should I take lomitapide?

Your doctor will perform blood tests to make sure lomitapide is safe for you to take.

Lomitapide is usually taken once daily, at least 2 hours after your evening meal. Your doctor may occasionally change your dose to make sure you get the best results. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended. Take this medicine with a full glass of water. Do not crush, chew, break, or open a lomitapide capsule. Swallow it whole.

Your doctor may have you take vitamin E or essential fatty acid supplements while you are taking lomitapide. Take only the type and amount of vitamins or supplements your doctor has prescribed. While using lomitapide, you may need frequent blood tests at your doctor’s office.

Lomitapide is only part of a treatment program that may also include diet, exercise, and weight control. Follow your doctor’s instructions very closely.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking lomitapide?

Grapefruit and grapefruit juice may interact with lomitapide and lead to unwanted side effects. Do not drink grapefruit juice while taking lomitapide. Avoid drinking alcohol. It may increase your risk of liver damage while you are taking lomitapide.

If you also take cholestyramine or colestipol, take these medicines at least 4 hours before or after you take lomitapide. Do not take either of these medicines at the same time you take lomitapide. Avoid eating foods that are high in fat or cholesterol. Lomitapide will not be as effective in lowering your cholesterol if you do not follow a cholesterol-lowering diet plan.

Lomitapide side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using lomitapide and call your doctor at once if you have signs of a liver problem, such as:

• nausea, upper stomach pain, loss of appetite;
• dark urine, clay-colored stools; or
• itching, or jaundice (yellowing of the skin or eyes).

• Common side effects may include:

• vomiting, gas, indigestion, stomach pain;
• diarrhea, constipation;
• chest pain; or
• weight loss.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Lomitapide Dosing Information

Usual Adult Dose for Hyperlipidemia:

Lomitapide should be taken with a glass of water on an empty stomach at least 2 hours after the evening meal.

Initial dose: 5 mg orally once daily. Dose should be escalated gradually based on acceptable safety and tolerability.

Dosing escalation: 5 mg orally daily for at least 2 weeks; then 10 mg orally daily for at least 4 weeks; then 20 mg orally daily for at least 4 weeks, then 40 mg orally daily for at least 4 weeks; then 60 mg orally daily

Maintenance dose: Should be individualized, taking into account the goal of therapy and the response to treatment

Maximum dose: 60 mg orally daily

Usual Adult Dose for Homozygous Familial Hypercholesterolemia:

Lomitapide should be taken with a glass of water on an empty stomach at least 2 hours after the evening meal.

Initial dose: 5 mg orally once daily. Dose should be escalated gradually based on acceptable safety and tolerability.

Dosing escalation: 5 mg orally daily for at least 2 weeks; then 10 mg orally daily for at least 4 weeks; then 20 mg orally daily for at least 4 weeks, then 40 mg orally daily for at least 4 weeks; then 60 mg orally daily

Maintenance dose: Should be individualized, taking into account the goal of therapy and the response to treatment

Maximum dose: 60 mg orally daily

What other drugs will affect lomitapide?

Many drugs can interact with lomitapide. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with lomitapide, especially:

• ambrisentan;
• colchicine;
• dabigatran;
• fexofenadine;
• loperamide (Imodium);
• maraviroc;
• saxagliptin or sitagliptin (for type 2 diabetes);
• tolvaptan;
• warfarin, Coumadin;
• birth control pills;
• drugs to treat cancer or leukemia–lapatinib, nilotinib, topotecan, vinblastine;
• heart or blood pressure medicine–aliskiren, digoxin, ranolazine;
• medicine to prevent organ transplant rejection–everolimus, sirolimus; or
• other cholesterol-lowering medications, especially atorvastatin, lovastatin, simvastatin.

• This list is not complete and many other drugs can interact with lomitapide. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

LDK-378

Novartis compound LDK378 receives FDA Breakthrough Therapy designation for ALK+ non-small cell lung cancer

• LDK378 is an investigational selective inhibitor of ALK[1], a target found in a variety of cancers including metastatic non-small cell lung cancer (NSCLC)
• Breakthrough Therapy designation is based on positive early data in patients with ALK+ NSCLC who have been previously treated with crizotinib
• First filing for LDK378 anticipated in early 2014

Basel, March 15, 2013 – Novartis announced today that its investigational compound LDK378 has received Breakthrough Therapy designation by the US Food and Drug Administration (FDA) for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who had progressed during treatment with, or were intolerant to, crizotinib. There are limited treatment options for patients with ALK+ NSCLC, who tend to be non-smokers and younger than NSCLC patients without an ALK translocation[2].

According to the FDA, Breakthrough Therapy designation is intended to expedite the development and review of drugs that treat serious or life-threatening conditions if the therapy has demonstrated substantial improvement over an available therapy on at least one clinically significant endpoint. The designation includes all of the fast track program features, as well as more intensive FDA guidance. The Breakthrough Therapy designation is a distinct status from both accelerated approval and priority review, which can also be granted to the same drug if relevant criteria are met[3].

“LDK378 is a strong example of our research approach, which focuses on identifying the underlying cause of disease pathways,” said Alessandro Riva, Global Head, Oncology Development & Medical Affairs, Novartis Oncology. “This Breakthrough Therapy designation will allow us to collaborate more closely with the FDA and potentially to expedite the availability of an important new treatment option for patients with ALK+ NSCLC.”

Initial results from a Phase I study investigating the maximum tolerated dose, safety, pharmacokinetics and antitumor activity of LDK378 in 88 patients with ALK+ advanced malignancies, as detected by an FDA-approved test and who had progressed during treatment with, or were intolerant to, crizotinib, were presented at the European Society of Medical Oncology 2012 annual congress. The data showed marked responses in a majority of patients with ALK+ NSCLC[1]. A response rate (including complete response [CR], partial response [PR] and unconfirmed PR) of 80% was observed in the patients who had experienced disease progression after crizotinib treatment[1].

Novartis has initiated two Phase II clinical trials to further evaluate the compound in this patient population with plans to initiate several Phase III clinical trials later this year. First regulatory filing is anticipated by early 2014.

About LDK378: LDK378 is a highly selective inhibitor of an important cancer target, anaplastic lymphoma kinase (ALK)[1],[4]. Because it is an investigational compound, the safety and efficacy profile of LDK378 has not yet been established. Access to this investigational compound is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of this compound. Because of the uncertainty of clinical trials, there is no guarantee that LDK378 will ever be commercially available anywhere in the world.

References
[1]	Shaw A, et al. Results of a First-in-Human Phase I Study of the ALK Inhibitor LDK378 in Advanced Malignancies. Abstract #4400. 2012 European Society for Medical Oncology (ESMO) Annual Meeting, Vienna, Austria.
[2]	Shaw A, et al. Targeting Anaplastic Lymphoma Kinase in Lung Cancer. Clin Cancer Res 2011;17:2081-2086.
[3]	U.S. Food and Drug Administration. Frequently Asked Questions: Breakthrough Therapies. Available at: http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/ SignificantAmendmentstotheFDCAct/FDASIA/ucm341027.htm. Accessed Mar 12, 2013.
[4]	Mehra R et al. First-in-Human Phase I Study of the ALK Inhibitor LDK378 in Advanced Solid Tumors. Abstract #3007. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.
[5]	American Cancer Society. Lung Cancer – Non-Small Cell Detailed Guide. Available at: http://www.cancer.org/Cancer/LungCancer-Non-SmallCell/DetailedGuide/non-small-cell-lung- cancer-what-is-non-small-cell-lung-cancer. Accessed Mar 12, 2013.

Read more: Novartis compound LDK378 receives FDA Breakthrough Therapy designation for ALK+ non-small cell lung cancer – FierceBiotech http://www.fiercebiotech.com/press-releases/novartis-compound-ldk378-receives-fda-breakthrough-therapy-designation-alk#ixzz2O5u7mAu4

TTP-488 for Alzheimer’s Disease

FDA Grants TransTech Pharma Inc. Fast Track Designation for TTP488 for the Treatment of Alzheimer’s Disease

 BusinessWire · Mar. 18, 2013 | Last Updated: Mar. 18, 2013 6:00 PM ET

TransTech Pharma Inc. announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for TTP488, a new small-molecule chemical compound being developed for the treatment of Alzheimer’s disease. TTP488 prevents the interaction of amyloid beta (Aβ), a material found in the cells of Alzheimer’s patients, and a member of the immunoglobulin supergene family of molecules known as the Receptor for Advanced Glycation Endproducts (RAGE). TTP488 is the first drug related to RAGE, a relatively new biological target in Alzheimer’s disease research, with demonstrated success in multiple clinical trials. TransTech Pharma discovered, developed and owns the rights to this drug candidate.

The FDA’s Fast Track designation is granted to development products intended for the treatment of a serious or life-threatening condition that demonstrate the potential to address unmet medical needs. The Fast Track program facilitates the development and expedites the review of qualifying new drugs. Under Fast Track designation, drugs are eligible for accelerated FDA approval and are likely to be considered appropriate to receive priority during the review process.

“We are very pleased to see that TTP488 has received Fast Track designation,” said Dr. Adnan Mjalli, Chairman and Chief Executive Officer of TransTech Pharma. “This development reflects a recognition that TT488 has the potential to address huge unmet medical needs for the treatment of millions of patients suffering from Alzheimer’s disease, a devastating and life-threatening disease with profound consequences for our aging population.”

About TTP488: Substantial data suggest that RAGE is involved in the pathogenesis of Alzheimer’s disease, and that sustained Aβ interaction with RAGE at the blood-brain barrier (BBB), or in neuronal or microglial cells, is an important element of amyloid plaque formation and chronic neural dysfunction. TTP488 is a novel, small-molecule, orally active antagonist of RAGE. In a recent double-blind clinical trial where data was taken over 18 months, TTP488 slowed cognitive decline in patients with mild to moderate Alzheimer’s disease. TransTech Pharma discovered and developed TTP488 using its proprietary drug discovery platform TTP Translational Technology®.

 

About TransTech Pharma: TransTech Pharma is a privately held, clinical-stage pharmaceutical company focused on the discovery, development, and commercialization of human therapeutics to fill unmet medical needs. The Company’s high-throughput drug discovery platform, Translational Technology®, translates the functional modulation of human proteins into safe and effective medicines. TransTech Pharma has a pipeline of small-molecule clinical and pre-clinical drug candidates for the treatment of a wide range of human diseases, including central nervous system disorders, diabetes, obesity, cardiovascular disease, inflammation and cancer. For further company information, visithttp://www.ttpharma.com.

Contacts

TransTech Pharma, Inc.
Adnan M.M. Mjalli, Ph.D, 336-841-7770
amjalli@ttpharma.com

 

Lymphoseek

FDA Approves Lymphoseek

FDA Approves Lymphoseek to Help Locate Lymph Nodes in Patients with Certain Cancers

March 13, 2013 — The U.S. Food and Drug Administration today approved Lymphoseek (technetium Tc 99m tilmanocept) Injection, a radioactive diagnostic imaging agent that helps doctors locate lymph nodes in patients with breast cancer or melanoma who are undergoing surgery to remove tumor-draining lymph nodes.

Lymph nodes filter lymphatic fluid that flows from the body’s tissues. This fluid may contain cancer cells, especially if the fluid drains a part of the body containing a tumor. By surgically removing and examining the lymph nodes that drain a tumor, doctors can sometimes determine if a cancer has spread.

Lymphoseek is an imaging drug that helps locate lymph nodes; it is not a cancer imaging drug. Lymphoseek is the first new drug used for lymph node mapping to be approved in more than 30 years. Other FDA-approved drugs used for lymph node mapping include sulfur colloid (1974) and isosulfan blue (1981).

“Removal and pathological examination of lymph nodes draining a primary tumor is an important diagnostic evaluation for some patients with breast cancer or melanoma,” said Shaw Chen, M.D., deputy director of the Office of Drug Evaluation IV in the FDA’s Center for Drug Evaluation and Research. “To use Lymphoseek, doctors inject the drug into the tumor area and later, using a handheld radiation detector, find lymph nodes that have taken up Lymphoseek’s radioactivity.”

Lymphoseek’s safety and effectiveness were established in two clinical trials of 332 patients with melanoma or breast cancer. All patients were injected with Lymphoseek and blue dye, another drug used to help locate lymph nodes.

Surgeons subsequently removed suspected lymph nodes for pathologic examination. Confirmed lymph nodes were examined for their content of blue dye and/or Lymphoseek. Results showed Lymphoseek and blue dye had localized most lymph nodes, although a notable number of nodes were localized only by Lymphoseek.

The most common side effects identified in clinical trials was pain or irritation at the injection site.

Lymphoseek is marketed by Navidea Biopharmaceuticals, Inc. based in Dublin, Ohio.

Source: FDA

Posted: March 2013