Newron, Zambon announce re-submission of safinamide NDA to FDA

In continuation of my update on safinamide 

Newron Pharmaceuticals S.p.A. ("Newron"), a research and development company focused on novel CNS and pain therapies, and its commercial and development partner Zambon S.p.A., an international pharmaceutical company, announced  that the NDA for safinamide has been re-submitted to the US FDA. This follows the announcement last week that the CHMP has given a positive opinion on safinamide for Europe.

The submission covers the indications "safinamide as add-on therapy to a stable dose of a single dopamine agonist" in early Parkinson's disease patients and "safinamide as add-on therapy to levodopa alone or in combination with other Parkinson's disease treatments" in mid-to late stage Parkinson's disease patients.

The first submission of safinamide to the US FDA was made in May 2014. On review, the FDA issued a Refusal to File (RTF) letter based on organizational and navigational problems, largely due relating to the hyperlinking of tables, folders and the organization of the table of contents in the submission.

Ravi Anand, Newron's CMO, stated: "Newron has been in frequent contact with the FDA to propose solutions to the technical issues and obtain their concurrence with the proposals. These discussions lead Newron to conclude that the RTF issues have been addressed in this submission."

Newron, Zambon announce re-submission of safinamide NDA to FDA

Can-Fite BioPharma completes RA Phase III study of lead drug candidate CF101

Can-Fite BioPharma Ltd.  a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, announced today that it completed the design of the Rheumatoid Arthritis (RA) Phase III study of its lead drug candidate CF101. Dr. M. Silverman, Can-Fite Medical Director, and Dr. Lee Simon, a key opinion leader in the field of autoimmune inflammatory diseases, designed the Phase III clinical study.

The Phase III study will be a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that will investigate the efficacy and safety of daily CF101 administered orally as a monotherapy for 12 weeks to patients with active RA. The study will have three arms, a 2 mg CF101 dose, a 3mg CF101 dose and placebo, given orally twice daily in the form of tablets. Approximately 300 patients are expected to be enrolled in the study, where sample size for each treatment group will be approximately 100 patients and will provide a statistical power of at least 90%. The study primary end point will be ACR 20 response at Week 12. The A3 adenosine receptor biomarker will be evaluated prior to treatment and its correlation to patients' response to the drug will be analyzed upon study conclusion.

Can-Fite BioPharma completes RA Phase III study of lead drug candidate CF101

Combination of bedaquiline and verapamil reduces side effects, improves outcomes for TB patients

In continuation of my update on Bedaquiline

While an effective treatment is available for combating multidrug-resistant tuberculosis, it carries serious side effects for patients. New research conducted at the Center for Tuberculosis Research at the Johns Hopkins University School of Medicine shows that lower doses of the toxic drug bedaquiline — given together with verapamil, a medication that's used to treat various heart conditions — can lead to the same antibacterial effects as higher toxic doses of bedaquiline. The combination of the two drugs could potentially shorten treatment time, reduce the side effects of bedaquiline and improve patient outcomes for those suffering from TB.

The study will be published in the January 2014 issue of Antimicrobial Agents and Chemotherapy. The lead author is William Bishai, M.D., Ph.D., co-director of the Center for Tuberculosis Research.

"Using a mouse model of tuberculosis, we have shown lower doses of bedaquiline together with verapamil have the same antibacterial effect as the higher toxic doses," says Shashank Gupta, Ph.D., a research fellow at Johns Hopkins. "A lower dose of bedaquiline will cause no or less severe side effects."

Two years ago, bedaquiline became the first drug in the last four decades to be approved by the U.S. Food and Drug Administration for the treatment of multidrug-resistant TB. The drug works by inhibiting an enzyme used by Mycobacterium tuberculosis to replicate and spread throughout the body. While it can be a lifesaving therapy against one of the world's deadliest diseases, bedaquiline can also cause serious side effects in the heart and liver. Therefore, strategies to reduce the dose of bedaquiline while retaining its antibacterial activity would provide significant benefits to patients.

"Shortening treatment regimens and reducing the required doses may be a promising strategy to reduce the incidence of bedaquiline-related adverse effects and thereby improve multidrug-resistant TB treatment outcomes," says Gupta.

Combination of bedaquiline and verapamil reduces side effects, improves outcomes for TB patients

FDA approves Myriad’s BRACAnalysis CDx for use with ovarian cancer drug

In continuation of my update on Olaparib

Myriad Genetics, Inc.    announced that it has received approval from the U.S. Food and Drug Administration (FDA) for BRACAnalysis CDx to be used as the only companion diagnostic in conjunction with AstraZeneca’s drug Lynparza™ (olaparib). Lynparza is the first poly ADP-ribose polymerase (PARP) inhibitor for patients with germline mutations in BRCA1/2 advanced ovarian cancer who have had three or more lines of chemotherapy. BRACAnalysis CDx is Myriad’s first FDA-approved companion diagnostic for use with a novel PARP inhibitor.

FDA approves Myriad’s BRACAnalysis CDx for use with ovarian cancer drug

Final Phase 1 data of zoptarelin doxorubicin Phase 1/2 trial published in Clinical Cancer Research

Aeterna Zentaris Inc. (NASDAQ: AEZS, TSX: AEZ) (the "Company")  announced that an article on final data for the Phase 1 portion of the ongoing Phase 1/2 trial in prostate cancer with zoptarelin doxorubicin (formerly AEZS-108), a hybrid molecule composed of a synthetic peptide carrier and a well-known chemotherapy agent, doxorubicin, has been published in the December issue of Clinical Cancer Research. The article outlines data previously disclosed in June 2013 at the American Society of Clinical Oncology's ("ASCO") Annual Meeting, which demonstrated the compound's safety profile and promising anti-tumor activity in heavily pre‑treated men with castration- and taxane-resistant prostate cancer. These results led to the current investigator-driven Phase 2 portion in this same indication under the supervision of lead investigator, Jacek Pinski, MD, PhD, of the USC Norris Comprehensive Cancer Center. Titled, "Phase I, Dose-Escalation Study of the Targeted Cytotoxic LHRH Analog AEZS-108 in Patients with Castration- and Taxane-Resistant Prostate Cancer", Liu SV, Tsao-Wei DD, Xiong S, Groshen S, Dorff TB, Quinn DI, Tai YC, Engel J, Hawes D, Schally AV, Pinski J., the article is available at this link: Clin Cancer Res.

Final Phase 1 data of zoptarelin doxorubicin Phase 1/2 trial published in Clinical Cancer Research

Broccoli can help reduce HGPS-related defects

In continuation of my update on broccoli...

Children who suffer from Hutchinson-Gilford Progeria syndrome age prematurely due to a defective protein in their cells. Scientists at Technische Universität München have now identified another important pathological factor: the system responsible for removing cellular debris and for breaking down defective proteins operates at lower levels in HGPS cells than in normal cells. The researchers have succeeded in reactivating protein breakdown in HGPS cells and thus reducing disease-related defects by using a substance from broccoli.

Most Hutchinson-Gilford Progeria Syndrome (HGPS) patients carry a mutation that produces a defective form of the protein lamin A. This defective protein is referred to as progerin. Normal lamin A is a key component of the matrix surrounding the DNA in the cell nucleus and plays a role in gene expression. By contrast, the defective form, progerin, is not functional but is nevertheless continuously synthesized. The result is that progerin accumulates in the nucleus and causes the cell to "age". Consequently, HGPS patients develop classic diseases of old age such as atherosclerosis, osteoporosis, heart attacks and strokes. The disease is therefore regarded as a possible model system for the natural aging process in cells.

A window on the cell nucleus

In order to find out which specific metabolic pathways are affected by the mutation and the defective protein, Prof. Karima Djabali and her team from the TUM School of Medicine and the Institute for Medical Engineering conducted a comparative study of diseased and healthy tissue cells in which they investigated the composition of proteins in the cell nuclei and looked for differences.

Broccoli can help reduce HGPS-related defects

Ganciclovir drug resistance may occur more frequently in cystic fibrosis patients

A drug called ganciclovir is given to lung transplant patients to protect against a life-threatening virus that is common after transplantation.

Ganciclovir reduces mortality due to the virus from 34 percent to between 3 and 6 percent. But between 5 percent and 10 percent of patients infected with the virus have strains that are resistant to the drug.

A Loyola University Medical Center study found that such resistance may occur more frequently in cystic fibrosis patients. These patients were found to have insufficient levels of the drug in their bloodstream, enabling the virus to continually replicate. This in turn may increase the chance that mutations will occur and result in drug resistance.

The study suggests that cystic fibrosis patients should be monitored to ensure there are therapeutic levels of ganciclovir in their bodies, said James Gagermeier, MD, first author of the study. The study is published online ahead of print in the journal Transplant Infectious Disease.

Ganciclovir drug resistance may occur more frequently in cystic fibrosis patients

Palatin begins bremelanotide phase 3 study for treatment of female sexual dysfunction

Palatin Technologies, Inc. (NYSE MKT: PTN), a biopharmaceutical company developing targeted, receptor-specific peptide therapeutics for the treatment of diseases with significant unmet medical needs and commercial potential, today announced that it has started its bremelanotide pivotal registration program. The Company has initiated its phase 3 reconnect study in the United States for the treatment of female sexual dysfunction (FSD).

"We are pleased to achieve this major milestone in the bremelanotide program with the initiation of our phase 3 reconnect study in the U.S," stated Carl Spana, Ph.D., President and CEO of Palatin. "This is a key step in our global strategy to bring bremelanotide to market for the millions of women who have FSD and are seeking a safe and effective treatment." Dr. Spana further stated that, "Our recent $30 million financing has provided the financial resources to start the bremelanotide phase 3 pivotal registration program and timing flexibility regarding partnering for the U.S. and other non-European territories."

Palatin begins bremelanotide phase 3 study for treatment of female sexual dysfunction

Can-Fite BioPharma begins dosing in CF102 Phase II liver cancer trial

Can-Fite BioPharma Ltd. , a biotechnology company advancing a pipeline of proprietary small molecule drugs that address cancer and inflammatory diseases, today announced that it has dosed the first patient in a Phase II trial for the treatment of hepatocellular carcinoma (HCC), the most common form of liver cancer.

The Phase II randomized, double-blind, placebo controlled trial is to be conducted in the U.S., Europe and Israel with an estimated 78 patients to be enrolled. CF 102 is being evaluated for efficacy and safety as a second-line treatment for advanced HCC in subjects with Child-Pugh B who failed Nexavar as a first line treatment. The first patient was dosed at the study's Israeli site, the Rabin Medical Center. The primary endpoint of the study is overall patient survival.

Can-Fite BioPharma begins dosing in CF102 Phase II liver cancer trial

Intriguing small molecule directs activity of key ‘clock proteins’

In research published in Nature Communications, Thomas Burris, Ph.D., chair of pharmacological and physiological science at Saint Louis University, reports intriguing findings about a small molecule that directs the activity of key "clock proteins," offering the potential to manage circadian rhythm and treat problems that are associated with its dysfunction, like sleep and anxiety disorders.

 

Circadian rhythm refers to biological processes that cycle every 24 hours. In mammals, the internal clock that maintains circadian rhythm is essential for normal physiological functions. The rhythms can, however, be disrupted, and dysregulation of circadian rhythm is associated with many disorders, including metabolic disease and neuropsychiatric disorders including bipolar disorder, anxiety, depression, schizophrenia and sleep disorders.

Burris and his colleagues examined compounds that target a protein called REV-ERB, which appears to play a key role in regulating mammals' internal clocks.

"It has been suggested that REV-ERB is a core component of our clock," said Burris. "Mice without it are arrhythmic. This study demonstrated that when we give mice a synthetic compound that turns REV-ERB on, it altered their circadian rhythm."

The team examined effects of the REV-ERB drug on patterns of sleep and wakefulness and found that the compound increases wakefulness, reduces REM and slow-wave sleep, and, notably, decreases anxiety.

This is an interesting finding because it is unusual. Frequently, drugs that increase arousal (wakefulness) also increase anxiety (ex. cocaine, amphetamines). And, vice versa: Drugs that decrease anxiety also decrease arousal (ex. benzodiazepines and ethanol). An exception to this common pattern is nicotine.

Intriguing small molecule directs activity of key ‘clock proteins’

Actavis receives complete response letter for nebivolol/valsartan FDC for treatment of hypertension

In continuation of my  update on Valsartan

Actavis plc , confirmed that the Company has received a complete response letter from the U.S. Food and Drug Administration (FDA) for its New Drug Application (NDA) for the fixed-dose combination (FDC) of nebivolol (below structure)  and valsartan for the treatment of hypertension.

"Although we are disappointed in the receipt of a complete response letter, Actavis remains committed to bringing treatments to market that address the significant public health issue of cardiovascular disease," said David Nicholson, Senior Vice President, Actavis Global Brands R&D. "Bystolic is a safe and effective option that is commonly used in combination with other antihypertensive medications to help patients reach blood pressure treatment goals. We will review the complete response and determine the appropriate next steps."

Actavis receives complete response letter for nebivolol/valsartan FDC for treatment of hypertension

Mirati begins dosage in MGCD265 Phase 1b clinical trial for NSCLC

Mirati Therapeutics, Inc. (NASDAQ: MRTX) today announced that the first patient with Non-Small Cell Lung Cancer (NSCLC) has been dosed in a Phase 1b clinical trial of MGCD265 in selected patients exhibiting genetic alterations of MET or Axl. In this segment of the study, one of the expansion cohorts will enroll patients with NSCLC and another will enroll patients with other solid tumors. Both cohorts will enroll only those patients that have specific MET driver mutations including MET gene point mutations, gene amplification, and MET or Axl gene rearrangements.

"In the dose escalation phase of this trial, we identified an optimal dose that achieved serum levels that we believe will result in greater than 90% inhibition of MET and Axl," said Charles M. Baum, M.D., Ph.D., president and CEO of Mirati. "We are focused on patients whose tumors harbor the specific MET and Axl genetic alterations that MGCD265 is designed to treat. By selecting and treating only those patients who carry the targeted mutations, there is strong rationale that we'll see proof of concept based on a high overall response rate in early 2015 that supports accelerated drug development."

Mirati begins dosage in MGCD265 Phase 1b clinical trial for NSCLC

FDA approves Namzaric drug for treatment of moderate to severe Alzheimer's disease

FDA approves Namzaric drug for treatment of moderate to severe Alzheimer's disease

Pre-clinical studies confirm TRXE-009 as new potential treatment for melanoma

Novogen Limited (ASX:NRT; NASDAQ: NVGN), Australian/US biotechnology company, announces that it has confirmed that its lead candidate product, TRXE-009, originally developed for the treatment of brain cancers, has been shown in pre-clinical studies also to be highly active against melanoma.

The Company believes this is an important breakthrough discovery for two reasons. The first is that it confirms that TRXE-009 is an important new potential treatment for melanoma, including for the treatment of secondary brain cancers due to melanoma, for which there currently are no effective therapies. The second is that it offers evidence for the first time of an hypothesized link between brain cancer and melanoma.

The link has long been considered a possibility because nerve cells and melanocytes (the melanin pigment-bearing cells in skin that lead to melanoma) have a common origin in the embryo known as the neural crest. This primitive tissue gives rise to the neural cells that go on to form the brain, spinal cord, and peripheral nerves, as well as cells that form the structures of the skull; melanocytes also come from this embryonic tissue. Up till now, no functional link has been found between brain cells and melanocytes, or between brain cancer and melanoma. TRXE-009 is the first compound to demonstrate the possibility of a common link, suggesting that is the first drug with the ability to identify cancers arising in cells that have the neural crest as their common origin.

Pre-clinical studies confirm TRXE-009 as new potential treatment for melanoma

Isis Pharmaceuticals begins ISIS-DMPK Rx clinical study in DM1 patients

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced  that it has initiated a study for ISIS-DMPKRx in patients with Myotonic Dystrophy Type 1 (DM1). DM1 is a rare genetic neuromuscular disease caused by the production of toxic dystrophia myotonica-protein kinase (DMPK) RNA in cells. ISIS-DMPKRx is specifically designed to reduce toxic DMPK RNA.

"The Myotonic Dystrophy Foundation is pleased that Isis is advancing to the next phase of clinical trials for ISIS-DMPKRx," said Molly White, executive director of the Myotonic Dystrophy Foundation. "Myotonic Dystrophy, the most common form of muscular dystrophy, is a devastating disease with no therapeutic option. Myotonic dystrophy research has accelerated significantly in the last 10 years, helping bring about the innovative science behind ISIS-DMPKRx, a drug that specifically targets the genetic defect that causes myotonic dystrophy type 1. We applaud Isis for investing in and leading drug development efforts for myotonic dystrophy type 1, and we appreciate the commitment Isis Pharmaceuticals has made to improve the lives of patients in our community."

"We have an innovative and productive partnership with Biogen Idec in developing drugs to treat severe and rare diseases, like DM1. In just under two and a half years, we have been able to discover and complete early development on ISIS-DMPKRx, which includes completing a Phase 1 single ascending-dose study in healthy volunteers. Today we advance this program into patients," said B. Lynne Parshall, chief operating officer at Isis. "The speed at which we have advanced ISIS-DMPKRx highlights the productive and collaborative nature of our partnership."

Isis Pharmaceuticals begins ISIS-DMPK Rx clinical study in DM1 patients