Long-term dasatinib findings support first-line use in CML

In continuation of my update on dasatinib

Final DASISION study findings confirm dasatinib to be an effective, long-term treatment for patients with a new diagnosis of chronic phase-chronic myeloid leukaemia (CP-CML).

 dasatinib

After 5 years, 61% of 259 patients randomly assigned to receive dasatinib 100 mg/day were still taking the tyrosine kinase inhibitor (TKI), while 63% of the 260 patients started on imatinib 400 mg/day continued with their treatment, the investigators report in the Journal of Clinical Oncology.

The primary endpoint of complete cytogenetic response (CCyR) at 5 years had been achieved by 28% of dasatinib-treated patients and 26% of their imatinib-treated counterparts, although the researchers note that these values may have been higher if bone marrow samples had been tested in the patients at the end of the study.

Cumulative 5-year rates of major molecular response (MMR) and molecular responses with a 4.5-log (MR4.5) reduction in BCR-ABL1 transcripts from baseline were also comparable in the dasatinib and imatinib treatment arms, at 76% versus 64%, and 42% versus 33%, respectively, say Jorge Cortes, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors.

Five-year estimated overall survival was 91.0% for the dasatinib group and 90.0% for those given imatinib. And estimated progression-free survival was a corresponding 85.0% and 86.0% with 4.6% and 7.3% of patients transforming to accelerated or blast phase CML during a period of follow-up that continued beyond TKI discontinuation.

In all, 84% of dasatinib-treated patients and 64% of imatinib-treated patients achievedBCR-ABL1 of 10% or less within 3 months of treatment. Compared with patients who did not reach this target, these individuals were more likely to achieve CCyR, MMR and MR4.5over 5 years, had higher rates of overall and progression-free survival, and were less likely to have transformation.

Cortes et al note that no new adverse effects were reported for dasatinib or imatinib by the end of the 5-year study period and just 15% and 11% of adverse effects were grade 3 or 4 in the groups, respectively.

Patients given dasatinib had higher rates of grade 3 or 4 neutropenia (29 vs 24%), anaemia (13 vs 9%) and thrombocytopenia (22 vs 14%) but lower rates of other nonhaematological side effects, except for any grade of pleural effusion (28.0 vs 0.8%). Discontinuation for drug-related side effects occurred in 16% and 7% of dasatinib- and imatinib-treated patients, respectively.

Pulmonary hypertension was reported in 5.0% and 0.4% of the dasatinib and imatinib groups, respectively, with 12 of the 14 diagnoses deemed to be drug related. Arterial ischaemic events were "uncommon" in both groups, affecting 5.0% and 2.0%, respectively.

However, there was a "disproportionate number" of deaths from infection in the dasatinib versus imatinib groups (11 vs 1), with seven deaths reported between 69 days and 4.5 years after dasatinib discontinuation.

"It will be important to prospectively and intentionally look at a possible imbalance in the occurrence of infections and, if present, determine a possible mechanism(s) for dasatinib-related infectious complications", the investigators comment.

"These results suggest that first-line dasatinib should continue to be considered a standard first-line therapy for patients with newly diagnosed CML-CP", the researchers conclude.

While patients given dasatinib were more likely to achieve early treatment milestones, the authors explain that the high rates of CCyR and overall survival in both treatment arms mean a longer follow-up period and larger study population are likely needed to demonstrate any significant difference in survival between the TKIs.

Diabetes Drug Victoza May Help the Heart: Study

In continuation of my update on liraglutide

The blood sugar-lowering drug Victoza (liraglutide) cuts the risk of heart attack and stroke in type 2 diabetes patients, a new study finds.

Heart disease is the leading cause of death among people with type 2 diabetes, the researchers noted.

The study was funded by the drug's maker, Novo Nordisk, and the U.S. National Institutes of Health. It included more than 9,300 adults from 32 countries who have type 2 diabetes and a high risk of heart disease.

About half took Victoza, while the other half took an inactive placebo. Both groups also took other medications for health problems, such as high blood pressure and high cholesterol, the study authors said.

Tracking patients for three years, the researchers found that compared with patients in the placebo group, people who took Victoza had a 13 percent lower risk of heart attack or stroke. They also had a 22 percent lower risk of death from heart disease; a 15 percent lower risk of death from any cause; and a 22 percent lower risk of new evidence of advanced kidney disease.

Some patients did discontinue the drug due to "gastrointestinal events," according to the report.

The study was presented June 13 at the American Diabetes Association's annual meeting, in New Orleans. It was also published simultaneously in the New England Journal of Medicine.

"I've been excited about liraglutide for a long time because I think it's unique," said study senior author Dr. John Buse. He directs the Diabetes Care Center at the University of North Carolina, Chapel Hill.

"This is the first diabetes drug that has shown across-the-board benefits for cardiovascular diseases, and this suggests it plays a role in treating atherosclerosis [hardening of the arteries], which is what leads to heart attacks and strokes," Buse said in a university news release.

One diabetes expert called the study "encouraging."

Victoza "is a relatively new medication, given by daily injection," said Dr. Allison Reiss, who runs the inflammation laboratory at Winthrop-University Hospital in Mineola, N.Y.

Still, the long-term effectiveness of the drug is unknown, Reiss added. "It will be important to follow these patients over the next few years to see whether [Victoza] benefits continue and to investigate how it is working," she said.

The researchers explained that Victoza is from a newer class of diabetes drugs known as GLP-1 agonists. These medications work in the pancreas to cut the production of an anti-insulin hormone called glucagon. The drugs boost insulin production and help control blood sugar levels.

As a secondary mechanism, Victoza also works on the brain to help lower appetite and boost feelings of "fullness" when eating, Buse's team explained.

Reiss noted that because of this activity, Victoza can help spur weight loss -- and that might be the prime factor driving the improvements in heart health.

Dr. Gerald Bernstein coordinates the Friedman Diabetes Program at Lenox Hill Hospital in New York City. He said that Victoza -- and other drugs in its class -- are being increasingly used, so "decreased cardiovascular risk is an important finding."

FDA Issues Complete Response Letter for Mycapssa New Drug Application

Chiasma, Inc. , a late-stage biopharmaceutical company focused on improving the lives of patients with rare and serious chronic diseases, today announced that it received a Complete Response Letter (CRL) from the United States (U.S.) Food and Drug Administration (FDA) regarding the company’s New Drug Application for Mycapssa (octreotide) capsules for the maintenance treatment of U.S. adult patients with acromegaly. The FDA issues CRLs to indicate that the review cycle for an application is complete and that the application is not ready for approval in its present form. 

Mycapssa, octreotide (RG3806) (formerly Octreolin)

About Mycapssa

Mycapssa is an investigational new oral drug proposed for the maintenance therapy of adult patients with acromegaly. If approved, octreotide capsules may be the first oral somatostatin analog approved for acromegaly. Octreotide capsules have been granted orphan designation in the United States and the European Union for the potential treatment of acromegaly.

Octreotide capsules are an investigational drug that has not been approved for use in any jurisdiction.

About Chiasma

Chiasma is a late-stage biopharmaceutical company focused on improving the lives of patients suffering from orphan diseases by developing and commercializing novel oral forms of therapies that are available today only by injection. The company’s lead product candidate is Mycapssa (octreotide) capsules, an investigational new drug developed with Chiasma’s Transient Permeability Enhancer (TPE®) technology to facilitate gastrointestinal absorption of unmodified drug into the bloodstream safely. Mycapssa is a proposed tradename, and this investigational new drug has not been approved for use in any jurisdiction. Using TPE® technology, Chiasma is evaluating additional proteins, peptides and small molecule drugs that are currently only available by injection but could potentially be converted to oral delivery. TPE® technology is potentially well suited for drugs with chronic indications, where frequent dosing is required and the need for an oral alternative is greatest. Chiasma is a Delaware corporation with a wholly-owned Israeli subsidiary. Mycapssa and TPE® are trademarks of Chiasma.

Cempra Completes NDA Submissions for Solithromycin in the Treatment of Community-Acquired Bacterial Pneumonia

Cempra, Inc.  , a clinical-stage pharmaceutical company focused on developing antibiotics to meet critical medical needs in the treatment of bacterial infectious diseases, announced the completion of its rolling submission of the New Drug Applications (NDA) for solithromycin to the U.S. Food and Drug Administration (FDA) for the treatment of community-acquired bacterial pneumonia (CABP). Based on the Qualified Infectious Disease Product (QIDP) designation by the FDA of solithromycin, Cempra has Priority Review and has been granted Fast Track for both the oral capsule and intravenous formulations for the treatment of CABP, which could result in an FDA decision on solithromycin's NDA within eight months, or by the end of 2016, based on the Prescription Drug User Fee Act (PDUFA) performance goals.

 Solithromycin

"Completion of the rolling submission of our first NDAs during Cempra's ten year anniversary year represents a major milestone for the company and a significant step toward our goal of developing antibiotics to meet the critical medical needs of patients in the treatment of bacterial infectious diseases," stated Prabhavathi Fernandes, Ph.D., president and chief executive officer of Cempra. "We believe the intravenous and capsule formulations will provide dosing flexibility that could lead to fewer hospital admissions, earlier discharge if admitted, and increased treatment of CABP on an outpatient basis. We are confident we have a strong data package for solithromycin."

"The management of CABP remains a challenge to healthcare professionals and I firmly believe that solithromycin has the potential to be a significant part of the treatment of this life threatening illness, given its published clinical efficacy and potential for multiple formulations," stated Thomas M. File, M.D., principal investigator for solithromycin clinical trials, Northeast Ohio Medical University. "Solithromycin's potency, spectrum of activity and tolerability could help to offset the rising problem of bacterial resistance, and it is gratifying to note that patients could be closer to benefiting from this potential new treatment."

The FDA has a 60-day filing review period to determine whether the NDAs are complete and acceptable for filing, and to confirm that Priority Review has been granted. Cempra expects to communicate the agency's decision regarding acceptance of the NDAs and its PDUFA date when it is known. Cempra's submissions in the EU remain on track for completion by the end of June 2016.

About Solithromycin

Solithromycin is a highly potent next-generation macrolide, the first fluoroketolide, which has potent activity against most macrolide-resistant strains. In vitro and in vivo studies have shown potent activity against S. pneumoniae as well as an extended spectrum of activity against CA-MRSA, streptococci, Haemophilus, enterococci, Mycobacterium avium and in animal models of malaria. It is also active against atypical bacteria, such as legionella, chlamydia, mycoplasma and ureaplasma, and against gonococci and other organisms that cause genitourinary tract infections. It is 8-16 times more potent than azithromycin against many bacteria and is active against azithromycin-resistant strains. Solithromycin's activity against resistant strains is driven by its ability to interact with three sites on the bacterial ribosome, compared to one for current macrolides. The binding to bacterial ribosomes and interaction with three ribosomal sites is expected to limit the development of bacterial resistance to solithromycin.

FDA Grants Soligenix “Fast Track” Designation for SGX943 for the Treatment of Melioidosis

Soligenix, Inc. (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, announced today that its SGX943 (dusquetide) development program has received “Fast Track” designation from the US Food and Drug Administration (FDA) as adjunctive therapy with other antibacterial drugs, for the treatment of melioidosis, a serious and potentially life-threatening condition.

 SGX943 (dusquetide)

Fast track is a designation that the FDA reserves for a drug intended to treat a serious or life- threatening condition and one that demonstrates the potential to address an unmet medical need for the condition. Fast track designation is designed to facilitate the development and expedite the review of new drugs. For instance, should events warrant, Soligenix will be eligible to submit a new drug application (NDA) for SGX943 on a rolling basis, permitting the FDA to review sections of the NDA prior to receiving the complete submission. Additionally, NDAs for fast track development programs ordinarily will be eligible for priority review, which imparts an abbreviated review time of approximately six months.

“We are very pleased to have been granted fast track designation from the FDA,” stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. “We believe that the FDA’s action in granting fast track designation validates the unmet medical need that currently exists for the treatment of melioidosis and for the potential key role SGX943 can serve as a therapy in this rare, life-threatening disease. We look forward to working with the federal government to advance this biodefense development program.”

About Melioidosis

Melioidosis is a potentially fatal infection caused by the Gram-negative bacillus, Burkholderia pseudomallei(Bps). Highly resistant to many antibiotics, Bps can cause an acute disease characterized by a fulminant pneumonia and a chronic condition that can recrudesce. There is no preventive vaccine or effective immunotherapy for melioidosis. Therefore, there is a significant medical need for improved prevention and therapy.

Bps and the closely related Burkholderia mallei (Bm) are considered possible biological warfare agents by the Department of Health and Human Services (DHHS) because of the potential for widespread dissemination through aerosol. Bps is classified as a Tier 1 biothreat and a category B priority pathogen by the NIAID and is a top 5 priority in the most recent Public Health Emergency Medical Countermeasure Enterprise (PHEMCE) Strategy document.

Bps infection (melioidosis) is a major public health concern in the endemic regions of Southeast Asia and Northern Australia. Moreover, the organism has a worldwide distribution and the full extent of global spread is likely underestimated. Bps activity is seen in Southeast Asia, South America, Africa, the Middle East, India, and Northern Australia. The highest pockets of disease activity occur in Northern Australia and Northeast Thailand, Burma and Vietnam, and is likely under-reported in China. In Northeast Thailand, the mortality rate associated with Bps infection is over 40%, making it the third most common cause of death from infectious disease in that region after HIV/AIDS and tuberculosis.

About SGX943

SGX943 is the drug product designation for the active ingredient dusquetide in the treatment of melioidosis. Dusquetide is an IDR, a new class of short, synthetic peptides that has a novel mechanism of action in that it has simultaneous anti-inflammatory and anti-infective activity. IDRs have no direct antibiotic activity but modulate host responses, increasing survival after infections with a broad range of bacterial Gram-negative and Gram-positive pathogens, as well as accelerating resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma and chemo- and/or radiation-therapy. Dusquetide has demonstrated safety in a Phase 1 clinical study in 84 healthy human volunteers and preliminary efficacy and safety in an exploratory Phase 2 clinical study in 111 patients with oral mucositis due to chemoradiation therapy for head and neck cancer. Dusquetide has also previously demonstrated efficacy in numerous animal disease models including melioidosis, mucositis, colitis, skin infection and other bacterial infections. Dusquetide and related analogs have a strong intellectual property position, including composition of matter. Dusquetide was developed pursuant to discoveries made by Professors B. Brett Finlay, PhD and Robert Hancock, PhD of the University of British Columbia.

Charleston Laboratories, Inc. and Daiichi Sankyo, Inc. Announce FDA Acceptance of New Drug Application (NDA) for CL-108

In continuation of my updates on hydrocodone, Promethazine & acetaminophen

Charleston Laboratories, Inc. and Daiichi Sankyo, Inc.  announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for CL-108   (is a novel bi-layered tablet containing 12.5mg of immediate release promethazine with a modified release of 7.5 mg of hydrocodone and 325mg of acetaminophen) for the relief of moderate to severe pain while preventing or reducing the associated opioid-induced nausea and vomiting (OINV). CL-108 is a fixed-dose, immediate-release bi-layered tablet with a rapid release layer containing 12.5 mg of promethazine and a second layer containing 7.5 mg of hydrocodone and 325 mg of acetaminophen. The FDA has set a target action date under the Prescription Drug User Fee Act (PDUFA) of January 31, 2017.

 promethazine

"With this NDA acceptance, patients are one step closer to being able to have an option for relieving pain while also preventing or minimizing the nausea and vomiting side effects of opioid treatment," said Paul Bosse, President and Chief Executive Officer of Charleston Laboratories, Inc. "At Charleston Laboratories, a key part of our mission is to develop and commercialize products that provide patients with novel solutions for improving their pain management. This acceptance represents an important contractual milestone under our relationship with Daiichi Sankyo."

"Daiichi Sankyo is dedicated to bringing innovative medicines to patients with unmet medical needs in the area of pain management," said Mahmoud Ghazzi, MD, PhD, President and Global Head of Development for Daiichi Sankyo. "We look forward to working closely with the FDA during the review process for CL-108 and support the Agency's efforts to foster the safe and responsible use of opioid medications."

The NDA for CL-108 is supported by two pivotal randomized, double-blind, placebo- and active-controlled Phase 3 clinical studies, one following oral surgery (molar removal) and the other after bunionectomy surgery (removal of bunions from the foot), as well as by an additional Phase 3 open-label, actual use safety study in patients with moderate-to-severe acute pain, or "flares," associated with osteoarthritis of the knee or hip. More than 1,000 patients have been enrolled in the CL-108 Phase 3 clinical trial program. A human abuse liability study has also been conducted.

Shionogi Announces Acceptance of NDA for Naldemedine for the Treatment of Opioid-Induced Constipation

Shionogi announced that the New Drug Application (NDA) submitted in the U.S. for naldemedine, a once-daily, oral 0.2 mg tablet, has been accepted for review. In the U.S., the proposed indication is for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain (CNCP). The target action date under the Prescription Drug User Fee Act (PDUFA) is March 23, 2017. The company also submitted an NDA in Japan on March 30, 2016 for the proposed indication of the treatment of OIC in adult patients.

Naldemedine is an investigational peripherally-acting mu-opioid receptor antagonist (PAMORA) being studied in the US for the treatment of OIC in adult patients with CNCP. Opioid-induced constipation is characterized by any of the following: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency after initiating opioid therapy.

"If approved, naldemedine will offer a new therapeutic option for chronic non-cancer pain patients living with opioid-induced constipation, a common and often debilitating condition," said Dr. John Keller, President and CEO, Shionogi Inc. "Shionogi is committed to developing new treatments to improve the lives of patients around the world. We look forward to working with U.S. and Japanese health authorities to bring naldemedine to market for their respective indications."

The NDA submissions include data supporting the efficacy and safety of naldemedine from the Phase III COMPOSE program.

About COMPOSE

The COMPOSE program is a global comprehensive development program comprised of seven clinical studies being conducted in patients with OIC and cancer or chronic non-cancer pain.

COMPOSE I and II were 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies. Both studies were designed to evaluate the efficacy and safety of naldemedine therapy versus placebo in patients on opioid therapy for at least three months and on a stable dose of opioids for at least four weeks, and who experience chronic non-cancer pain accompanied by OIC. The sample population for COMPOSE I and II included 547 and 553 patients, respectively.

Shionogi previously announced that naldemedine met its primary and key secondary endpoints in COMPOSE I, II and IV. COMPOSE IV was conducted in Japan.

In the studies, a bowel movement occurring within 24 hours after rescue laxative therapy was not considered a spontaneous bowel movement (SBM).

About Opioid-Induced Constipation (OIC)

Opioid-induced constipation (OIC) is characterized by any of the following after initiating opioid therapy: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency.1 Approximately half of all chronic non-cancer pain patients who have OIC are dissatisfied with laxatives.2 Managing OIC and its clinical consequences places a significant burden on the healthcare system and the patient.

Shionogi Announces Acceptance of NDA for Naldemedine for the Treatment of Opioid-Induced Constipation

FDA Issues Complete Response Letter for Apadaz New Drug Application

KemPharm, Inc.  a clinical-stage specialty pharmaceutical company engaged in the discovery and development of proprietary prodrugs,  announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the New Drug Application (NDA) for Apadaz™ (benzhydrocodone and acetaminophen), KemPharm’s investigational abuse-deterrent product candidate for the short-term management of acute pain.

 benzhydrocodone         acetaminophen

The FDA issues CRLs to indicate that the Agency considers the review cycle for an application is complete and that the application is not ready for approval in its present form. Included in the CRL is guidance that describes all specific deficiencies that the FDA has identified in the application. When possible, the FDA recommends actions that the applicant may take to place the application in condition for approval.

“After last week’s amendment request, a Complete Response Letter from the FDA was received for the Apadaz NDA,” said Travis C. Mickle, Ph.D., President and CEO of KemPharm. “We are currently evaluating the points raised in the CRL and intend to request an End of Review meeting with the Agency to determine the pathway forward for Apadaz.”

Allergan Announces FDA Acceptance of NDA Filing for Oxymetazoline HCI Cream 1.0%

Allergan plc  announced that the New Drug Application (NDA) filing for oxymetazoline HCl cream 1.0%, an investigational topical prescription product for the treatment of persistent facial erythema (redness) associated with rosacea in adults, has been accepted by the U.S. Food and Drug Administration (FDA) for standard review. Allergan expects the Prescription Drug User Fee Act (PDUFA) date to be in the first half of 2017.

"While rosacea is a common chronic skin condition that affects more than 16 million people in the U.S. alone1, there is a significant unmet need in effective, FDA-approved treatments for the condition," said David Nicholson, Chief R&D Officer, Allergan. "The NDA filing of oxymetazoline speaks to our strong commitment to ongoing innovation of our medical dermatology portfolio, and we look forward to bringing a new treatment option to patients with rosacea."

About Oxymetazoline

Oxymetazoline is a sympathomimetic agonist that is selective for the α1A-adrenoceptor over other α1-adrenoceptors and non-selective for the α2-adrenoceptors. As such, oxymetazoline is a potent vasoconstrictor of the cutaneous microvasculature. The NDA submission for oxymetazoline HCL cream 1.0% was based on data collected from two phase 3 pivotal clinical trials of a 29-day treatment duration and a 1-year open label clinical trial. These studies enrolled male and female patients ≥ 18 years of age with moderate to severe persistent facial erythema associated with rosacea.

AstraZeneca Receives Complete Response Letter from FDA for Sodium Zirconium Cyclosilicate (ZS-9) for Hyperkalemia

AstraZeneca today announced that the US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the New Drug Application (NDA) for sodium zirconium cyclosilicate (ZS-9), the investigational medicine being developed for the treatment of hyperkalemia (high potassium level in the blood serum) by ZS Pharma, a wholly-owned subsidiary of AstraZeneca.

The CRL refers to observations arising from a pre-approval manufacturing inspection. The FDA also acknowledged receipt of recently-submitted data which it has yet to review. The CRL does not require the generation of new clinical data. AstraZeneca and ZS Pharma are evaluating the      (see structure of  ZS-9 (sodium zirconium cyclosilicate) content of the CRL and will work closely with the FDA to determine the appropriate next steps for the NDA.AstraZeneca remains committed to the development of sodium zirconium cyclosilicate as a treatment option for patients with hyperkalemia. Interactions are ongoing with other health authorities in the European Union and Australia, where sodium zirconium cyclosilicate is currently under separate regulatory review.

About Sodium Zirconium Cyclosilicate (ZS-9) for Oral Suspension

Sodium zirconium cyclosilicate (ZS-9) is an insoluble, non-absorbed compound with a structure that was designed to preferentially trap potassium ions. The unique potassium selectivity of sodium zirconium cyclosilicate enables high in-vitro binding capacity for potassium ions even in the presence of other competing ions. Sodium zirconium cyclosilicate has been studied in three double-blind, placebo controlled trials and in one ongoing 12 month open label clinical trial in patients with hyperkalemia which represents over 1,600 patients treated. Sodium zirconium cyclosilicate is an investigational product that is not currently approved for any indication in any market.

About Hyperkalemia

Hyperkalemia (high potassium levels > 5.0 mEq/L in the blood serum) occurs in 23-47% of patients with advanced chronic kidney disease and/or chronic heart failure, and may lead to cardiac arrest and death (mortality of up to 30% in patients with severe hyperkalemia if not treated rapidly). Treatment with common heart medicines (RAAS inhibitors) can also be responsible for increases in hyperkalemia. Current therapeutic options are limited, leaving high unmet medical need.

Lexicon Announces FDA Priority Review of NDA for Telotristat Etiprate for the Treatment of Carcinoid Syndrome

Lexicon Pharmaceuticals, Inc.  announced that the U.S. Food and Drug Administration has accepted for filing the New Drug Application for telotristat etiprate, an oral drug for the treatment of carcinoid syndrome. The FDA has granted a Priority Review of the NDA filing and set a Prescription Drug User Fee Act (“PDUFA”) target action date of November 30, 2016.

“The granting of priority review by the FDA underscores the need for improving the lives of the patients and caregivers who live with carcinoid syndrome on a daily basis,” said Lexicon President and Chief Executive Officer, Lonnel Coats. “If approved, telotristat etiprate would be the only approved therapy for patients who are no longer able to control their carcinoid syndrome with the current standard of care alone.”

Carcinoid syndrome is a rare disease affecting thousands of cancer patients with metastatic neuroendocrine tumors (mNETs) that have spread to the liver and other organs from the gastrointestinal tract. The condition is characterized by frequent and debilitating diarrhea that often prevents patients from leading active, predictable lives, as well as facial flushing, abdominal pain, fatigue and, over time, heart valve damage.

About Telotristat Etiprate

Discovered using Lexicon’s unique approach to gene science, telotristat etiprate is the first investigational drug in clinical studies to target tryptophan hydroxylase, an enzyme that triggers the excess serotonin production within mNET cells that leads to carcinoid syndrome. While existing treatments for carcinoid syndrome work to reduce the release of serotonin outside tumor cells, telotristat etiprate works at the source to reduce serotonin production within the tumor cells. By specifically inhibiting serotonin production, telotristat etiprate seeks to control this important driver of carcinoid syndrome and, in turn, provide patients with more control over their disease.

Telotristat etiprate has received Fast Track and Orphan Drug designation from the U.S. Food and Drug Administration.

Lexicon retains rights to market telotristat etiprate in the U.S. and Japan, and is building the in-house commercial infrastructure to serve the U.S. market. Lexicon has a license and collaboration agreement with Ipsen to commercialize telotristat etiprate in Europe and other countries outside the U.S. and Japan.

Radius Announces FDA Acceptance for Filing of NDA for for the Treatment of Postmenopausal Women with Osteoporosis

Radius Health, Inc. ), a science-driven biopharmaceutical company that is committed to developing innovative therapeutics in the areas of osteoporosis, oncology and endocrine diseases, announced that its New Drug Application (NDA) for abaloparatide—SC has been accepted for filing by the U.S. Food and Drug Administration (FDA). The acceptance of the NDA reflects the FDA's determination that the application is sufficiently complete to permit a substantive review.

"The FDA's acceptance for filing of our abaloparatide-SC NDA is a major milestone for Radius and we look forward to continuing to work with the FDA as they review our application," said Robert E. Ward, President and CEO of Radius Health. "Given the high unmet medical need in osteoporosis, we believe that abaloparatide-SC, if approved, has the potential to become a promising new treatment option for the approximately 10 million postmenopausal women with osteoporosis, many of whom remain untreated."

The NDA is supported by data from the entire abaloparatide-SC development program, including the results from the 18-month Phase 3 ACTIVE trial in 2,463 postmenopausal women with osteoporosis and the first six months of the ACTIVExtend trial in 1,139 of the ACTIVE participants. Positive results for abaloparatide-SC treatment groups from the ACTIVE and ACTIVExtend trials have met the primary and secondary endpoints essential for submission of the NDA, including the primary endpoint of reduction of vertebral fractures as well as key endpoints of reduction of nonvertebral, clinical, and major osteoporotic fractures. In these and the other trials submitted in the NDA, abaloparatide-SC administered at a dose of 80 mcg daily was generally safe and well tolerated in postmenopausal women with osteoporosis.

As previously reported, Radius submitted a Centralised Marketing Authorisation Application (MAA) for abaloparatide-SC in the European Union on November 17, 2015, which was validated by the European Medicines Agency (EMA) in December 2015, and is currently undergoing active regulatory assessment by the Committee for Medicinal Products for Human Use of the EMA (CHMP). The EMA has granted Radius an additional 3-month extension to the procedural timetable for response in the ongoing MAA assessment. As a result of this extension to the procedural timetable, the Company now anticipates that the CHMP may adopt an Opinion regarding the MAA in late 2016 or in 2017.

Abaloparatide-SC is an investigational treatment for postmenopausal women with osteoporosis and its safety and efficacy have not been established.

Teva Announces FDA Approval of ProAir RespiClick (albuterol sulfate) Inhalation Powder for Pediatric Asthma Patients Ages 4 to 11

Teva Pharmaceutical Industries Ltd.,  announced  that the U.S. Food and Drug Administration (FDA) has approved ProAir RespiClick (albuterol sulfate) Inhalation Powder for the treatment or prevention of bronchospasm in children 4 to 11 years of age with reversible obstructive airway disease and for the prevention of exercise-induced bronchospasm (EIB).

ProAir RespiClick was approved by the FDA for use in patients 12 years of age and older in March 2015 and remains the only breath-activated, multi-dose, dry powder, short-acting beta-agonist (SABA) inhaler available in the U.S.

Flexion Therapeutics Receives Positive Guidance from FDA on NDA Submission for Zilretta for Osteoarthritis of the Knee

Flexion Therapeutics, Inc. announces that yesterday it received written responses from the U.S. Food & Drug Administration (FDA) to questions the company had submitted in advance of a pre-NDA meeting regarding Flexion's lead product candidate, Zilretta (also known as FX006). The FDA clearly indicates in its responses that the safety and efficacy data from the registration program for Zilretta are "acceptable to support filing of an NDA submission." Based on this positive FDA feedback, the in-person pre-NDA meeting has become unnecessary and the FDA responses will serve as the official meeting minutes.

Michael Clayman, M.D., President and Chief Executive Officer of Flexion, stated, "The endorsement from the FDA for the Zilretta NDA submission represents a major milestone in the development of this drug candidate and brings us one step closer to making it available to the many millions of knee osteoarthritis (OA) patients who lack good pain-relief options. We intend to submit the NDA in the fourth quarter of this year."

Allergan Receives FDA Approval of Teflaro (ceftaroline fosamil) for Pediatric Patients

Allergan plc, a leading global pharmaceutical company,  announced the U.S. Food and Drug Administration (FDA) has approved the company's supplemental New Drug Application (sNDA) for Teflaro (ceftaroline fosamil), granting new indications for pediatric patients 2 months of age to less than 18 years of age with acute bacterial skin and skin structure infections (ABSSSI), including infections caused by methicillin-resistant Staphylococcus aureus (MRSA), and community-acquired bacterial pneumonia (CABP) caused by Streptococcus pneumoniae and other designated susceptible bacteria.

"The impact of ABSSSI and CABP among children is significant, as these infections often require hospitalization and are met with limited pediatric treatment options, particularly as resistance increases among the pathogens that cause these infections," said David Nicholson, Chief R&D Officer, Allergan. "These new indications are yet another testament to our ongoing research and development in anti-infectives to address the evolving challenges of serious infections. Importantly, it allows us to educate physicians on the data they need to prescribe Teflaro to appropriate pediatric patients in need of an option that is safe and effective against some of the most difficult-to-treat pathogens in ABSSSI and CABP."

ABSSSI and CABP are common causes of healthcare visits and hospitalizations among children. Studies show more than 70,000 hospitalizations for ABSSSI occur among children per year – a rate that has more than doubled over the past 13 years.1 A study conducted by the Centers for Disease Control and Prevention (CDC) also found children younger than 5 years of age accounted for 70 percent of children hospitalized for community-acquired pneumonia.

These new indications were approved based on results from clinical studies evaluating TEFLARO in pediatric patients (2 months to less than 18 years of age), including one active-controlled study in ABSSSI and two active-controlled studies in CABP. In the ABSSSI active-controlled study, the efficacy and safety of Teflaro was compared with vancomycin or cefazolin (each with optional aztreonam). In the CABP studies, Teflaro was compared with ceftriaxone. Use of Teflaro in pediatric patients 2 months to less than 18 years of age is supported by evidence from adequate and well-controlled studies of Teflaro in adults, as well as additional pharmacokinetic and safety data from pediatric trials.

The primary objective of the pediatric ABSSSI and CABP studies was to evaluate the safety and tolerability of Teflaro. These studies were not powered for comparative inferential efficacy analysis, and no efficacy endpoints were identified as primary.

To evaluate the treatment effect of Teflaro in the ABSSSI pediatric trial, an analysis was conducted in 159 patients with ABSSSI in the Modified Intent-to-Treat (MITT) population. This analysis evaluated responder rates based on achieving both cessation of lesion spread and absence of fever on Study Day 3. Patients treated with Teflaro showed a higher response at Study Day 3 versus the comparator group, with clinical response achieved in 80.4 percent (86/107) of patients treated with Teflaro and 75 percent (39/52) of patients in the comparator group, with a treatment difference of 5.4 percent (95 percent Confidence Interval [CI] -7.8, 20.3). Clinical cure rates at the test of cure (TOC) visit (8 to 15 days after the end of therapy) for the ABSSSI pediatric trial were 94.4 percent (101/107) for patients treated with Teflaro and 86.5 percent (45/52) for the comparator, with a treatment difference of 7.9 (95 percent CI -1.2, 20.2).

To evaluate the treatment effect of Teflaro in the CABP trial submitted for this pediatric filing, an analysis was conducted in 143 patients with CABP in the MITT population. This analysis evaluated responder rates at Study Day 4 based on achieving improvement in at least two out of seven symptoms (cough, dyspnea, chest pain, sputum production, chills, feeling of warmth/feverish and exercise intolerance or lethargy), and worsening in none of these symptoms. The clinical response at Study Day 4 was 69.2 percent (74/107) for patients treated with Teflaro and 66.7 percent (24/36) for the comparator, with a treatment difference of 2.5 percent (95 percent CI -13.9, 20.9). Clinical cure rates at TOC were 87.9 percent (94/107) for patients treated with TEFLARO and 88.9 percent (32/36) for the comparator, with a treatment difference of -1.0 (95 percent CI -11.5, 14.1).

Results from the clinical studies in pediatric patients showed that Teflaro demonstrated a safety profile that was compatible with treatment of ABSSSI and CABP at the clinical dosages studied. The safety findings were similar to those seen in the adult studies, and no safety concerns were identified beyond those already known to be cephalosporin class effects.

Teflaro is the first and only cephalosporin indicated in adults and pediatric patients 2 months of age and older for the treatment of ABSSSI and CABP due to designated susceptible pathogens that can be administered by intravenous (IV) infusion in five minutes to one hour.