Fight against Ventilator-Associated Pneumonia....

In continuation of my update on "Pneumonia and its prevention..."

When I read an article from  Emedicine,  was surprised to see the analysis by the author. I quote the following lines...

 Hospital-acquired pneumonia (HAP) is pneumonia that develops 48 hours or longer after admission to a hospital.

• Ventilator-associated pneumonia (VAP) is pneumonia that develops 48 hours or longer after mechanical ventilation is given by means of an endotracheal tube or tracheostomy.
• Health care–associated pneumonia is pneumonia that occurs in persons in one of the following groups:
  • Patients who have been hospitalized in an acute care facility for 2 or more days within 90 days of the infection
  • Residents of a nursing home or long-term care facility
  • Patients who received intravenous antibiotic therapy, chemotherapy, or wound care within the last 30 days of the current infection
  • Patients who receive hemodialysis in any setting

HAP is the second most common nosocomial infection. HAP increases a patient's hospital stay by approximately 7-9 days and can increase hospital costs by an average of $40,000 per patient. and 

 Frequency

VAP is a complication in as many as 28% of patients who receive mechanical ventilation. The incidence of VAP increases with the duration of mechanical ventilation. Estimated rates are 3% per day for the first 5 days, 2% per day for days 6-10, and 1% per day after day 10.

Mortality/Morbidity

The crude mortality rate for VAP is 27-76%. Pseudomonas or Acinetobacter pneumonia is associated with increased mortality rates compared with other organisms. Studies have consistently shown that a delay in starting appropriate and adequately dosed antibiotic therapy increases the mortality risk...

We had "International Infection Prevention Week" a forth night ago,  but still we need to create awareness about such infections.   I think we need to give due importance for VAP too. Though,  there are many organizations, which are trying to create awareness and solutions for this problem, I find Kimberly Clark corporation's efforts really  interesting and  commendable. So let us join hands with the corporation to spread the awareness....

One can get more info with the link :

http://vap.kchealthcare.com

FDA Approves Xenleta (lefamulin) to Treat Community-Acquired Bacterial Pneumonia (CABP)

Nabriva Therapeutics plc (NASDAQ: NBRV), a biopharmaceutical company engaged in the commercialization and development of innovative anti-infective agents to treat serious infections, announced the U.S. Food and Drug Administration (FDA)  approval of Nabriva’s new drug applications for the oral and intravenous (IV) formulations of Xenleta (lefamulin) for the treatment of community-acquired bacterial pneumonia (CABP) in adults. As the first IV and oral antibiotic with a novel mechanism of action approved by the FDA in nearly two decades, Xenleta represents an important new empiric monotherapy treatment option for adults with CABP.

“Today’s approval of Xenleta is a significant breakthrough in the collective fight against the growing threat of antimicrobial resistance and provides a desperately needed IV and oral empiric monotherapy treatment option for adults with CABP,” said Ted Schroeder, chief executive officer of Nabriva Therapeutics. “We are especially proud of this approval because Xenleta was discovered in our labs over a decade ago and the entire development program was designed and executed by our dedicated and passionate team. We are indebted to the patients and researchers who collaborated with us and are excited to bring to patients and healthcare providers a novel, short course, empiric monotherapy treatment option for CABP. Xenleta has a mechanism of action that is different than other approved antibiotics, resulting in a low propensity for the development of resistance, as well as a lack of cross-resistance with the beta-lactam, fluoroquinolone, glycopeptide, macrolide, and tetracycline antibiotic classes. Xenleta has a targeted in vitro spectrum of activity against the most common causative Gram-positive, Gram-negative and atypical pathogens associated with CABP, which aligns with the principles of antimicrobial stewardship.”

“The gravity of antimicrobial resistance cannot be overstated, particularly in the context of treating pneumonia,” said Julio Ramirez, MD, FACP, Professor of Medicine, and Chief within the Division of Infectious Diseases, University of Louisville School of Medicine. “As an infectious disease specialist who treats CABP patients in the hospital setting, I am grateful to have both a new IV and oral option that gives me confidence that my patients will continue to receive appropriate therapy once they are discharged from the hospital.”

Xenleta is available for oral (600 mg every 12 hours) and IV (150 mg every 12 hours) administration with a short 5-to-7 day course of therapy. Clinicians can initiate patients on IV or oral therapy, allowing for potential avoidance of hospitalization, or can transition from IV to oral therapy, which may expedite discharge from the hospital. Currently, the median length of stay for patients with pneumonia is 3-to-4 days, resulting in approximately $17 billion in hospital costs per year in the United States. The opportunity to avoid a hospital admission or to discharge a patient earlier on oral therapy benefits patients and may result in significant savings to the health system.

Both the IV and oral formulations of Xenleta were granted Qualified Infectious Disease Product (QIDP) and Fast Track designation by the FDA. The FDA approval was based on a clinical development program supported by a robust data package, including two pivotal, Phase 3 trials (known as LEAP 1 and LEAP 2) that evaluated the safety and efficacy of IV and oral Xenleta compared to moxifloxacin in the treatment of adults with CABP. LEAP 1 was designed to evaluate 5-to-7 days of IV/oral therapy of Xenleta versus 7-days of IV/oral moxifloxacin, with or without linezolid, with both treatment groups having the option to switch from IV to oral administration after 3-days. LEAP 2 evaluated 5-days of oral Xenleta versus 7-days of oral moxifloxacin. LEAP 1 showed comparable efficacy with moxifloxacin, with or without linezolid, while LEAP 2 showed comparable efficacy with moxifloxacin, with two fewer days of therapy. Xenleta was generally well tolerated in both LEAP 1 and LEAP 2.

“Emergency departments across the country treat hundreds of thousands of patients with CABP each year. Many of these patients, especially elderly patients with comorbidities, are admitted solely because of the lack of an effective and well-tolerated oral treatment option” said Philip Giordano, MD, Vice Chairman of Emergency Medicine at the Orlando Regional Medical Center. “With a new oral antibiotic option that has been shown to be as effective as a respiratory fluoroquinolone, possessing a favorable side effect profile, we can consider sending more patients home directly from the emergency department and avoid costly hospitalizations, which is good for both patient care and the health system.”

Pneumonia is an infection of the lung that can be serious and fatal, especially among older adult patients with comorbidities. There are approximately five million cases of pneumonia in the U.S. each year, and pneumonia is the fifth leading cause of hospitalization and one of the leading causes of infection-related death. Streptococcus pneumoniae is the most common cause of bacterial pneumonia in the U.S. According to recent data from the SENTRY Antimicrobial Surveillance Program, in the U.S., approximately 30 to 60 percent of S. pneumoniae, depending on region, are macrolide resistant. In addition to macrolides, fluoroquinolones are another common treatment option for CABP. This broad-spectrum class is an effective option, however fluoroquinolones carry boxed warnings for several significant safety concerns.

Nabriva expects Xenleta will be available through major U.S. specialty distributors in mid-September 2019. Xenleta will have a wholesale acquisition (WAC) price of $205 per IV patient treatment day and $275 per oral patient treatment day.

“Offering clinicians and patients a new treatment option for CABP that addresses the urgent and growing threat of antimicrobial resistance is our top priority. With that in mind, our team has been working hard to make Xenleta available in the weeks ahead to ensure that patients with CABP who can benefit from this new treatment option can access it,” said Schroeder.

About Xenleta

Xenleta (lefamulin) is a first-in-class semi-synthetic pleuromutilin antibiotic for systemic administration in humans discovered and developed by the Nabriva Therapeutics team. It is designed to inhibit the synthesis of bacterial protein, which is required for bacteria to grow. Xenleta’s binding occurs with high affinity, high specificity and at molecular sites that are different than other antibiotic classes. Based on results from its two global, Phase 3 clinical trials, Nabriva Therapeutics believes Xenleta is well-positioned for use as a first-line monotherapy for the treatment of CABP due to its novel mechanism of action, targeted spectrum of activity, resistance profile, achievement of substantial drug concentration in lung tissue and fluid, availability of oral and IV formulations and a generally well-tolerated safety profile. Nabriva Therapeutics believes XENLETA represents a potentially important new treatment option for the approximately five million adults in the United States diagnosed with pneumonia each year.

In LEAP 1 and LEAP 2 (pooled), the median age of patients treated with Xenleta was 61 (range 19-97) years; 42% of patients were 65 years or older and 18% of patients were 75 years or older. In both trials, approximately half of Xenleta-treated patients had impaired renal function and the most common other comorbidities included hypertension, asthma/COPD and diabetes mellitus. These baseline characteristics were broadly representative of the adult patient population with CABP. 

In LEAP 1, Xenleta demonstrated non-inferiority compared to moxifloxacin, with or without linezolid, for the FDA primary endpoint of early clinical response (ECR) assessed 72 to 120 hours following initiation of therapy in the intent to treat (ITT) patient population (ECR rate = 87.3% for Xenleta and 90.2% for moxifloxacin, with or without linezolid; treatment difference -2.9 [95% confidence interval (CI) -8.5, 2.8]). In LEAP 2, 5-days of oral Xenleta also demonstrated non-inferiority to 7-days of oral moxifloxacin for the ECR endpoint in the ITT population (ECR rate = 90.8% for Xenleta and 90.8% moxifloxacin; treatment difference 0.1 [95% confidence interval (CI) -4.4, 4.5]). Importantly, high-risk patients 65 years and older achieved a similar ECR rate as those less than 65 years of age. The most common adverse reactions in patients receiving Xenleta in LEAP 1 (IV and oral) were administration site reactions, hepatic enzyme elevation, nausea, hypokalemia, insomnia, and headache in LEAP 1, and in LEAP 2 (oral only) diarrhea, nausea, vomiting and hepatic enzyme elevation. Few discontinuations due to adverse reactions were reported (3.3% in both treatment arms) and the 28-day mortality was low and balanced between treatment groups [8 patients (1.2%)] and [7 patients (1.1%)] for Xenleta and comparator, respectively from pooled data for LEAP 1 and LEAP 2.   

https://www.drugbank.ca/drugs/DB12825

https://en.wikipedia.org/wiki/Lefamulin

FDA Approves Zevtera (ceftobiprole medocaril sodium) for Bacteremia, Skin and Skin Structure Infections, and Pneumonia

Basilea Pharmaceutica Ltd, Allschwil (SIX: BSLN), a commercial-stage biopharmaceutical company committed to meeting the needs of patients with severe bacterial and fungal infections, announced today that the US Food and Drug Administration (FDA) approved Zevtera® (ceftobiprole medocaril sodium for injection), for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including those with right-sided infective endocarditis, and adult patients with acute bacterial skin and skin structure infections (ABSSSI) and for adult and pediatric patients (3 months to less than 18 years old) with community-acquired bacterial pneumonia (CABP).

David Veitch, Chief Executive Officer of Basilea, said: “We are excited with the US approval of Zevtera. The positive decision by the FDA is a key milestone towards bringing Zevtera to patients in the US. Zevtera has 10 years of market exclusivity from the date of approval and we believe the US provides the most important global commercial opportunity for the brand.”

Dr. Marc Engelhardt, Chief Medical Officer of Basilea, stated: “We are very pleased that the FDA approved Zevtera for all three indications that were submitted with the NDA, including a pediatric labelling. This approval is a landmark for ceftobiprole and reflects its broad clinical utility. The indication in adult patients with Staphylococcus aureus bacteremia, including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates, MSSA and MRSA, addresses a real medical need, as current treatment options are limited.”

The New Drug Application (NDA) was supported by clinical efficacy and safety data from the phase 3 studies ERADICATE (SAB)1 and TARGET (ABSSSI),2 and a phase 3 study in CABP.3 The ERADICATE study was the largest double-blind randomized registrational study conducted for a new antibiotic treatment in SAB.

Vance G. Fowler, Jr., M.D., Professor in the Departments of Medicine and Molecular Genetics & Microbiology at the Duke University School of Medicine and academic lead investigator of the ERADICATE study, commented: “Complicated Staphylococcus aureus infections have a high mortality rate and are associated with substantial morbidity. We need more options for treating these infections, especially if MRSA is involved.”

Thomas Holland, M.D., Associate Professor in the Department of Medicine at the Duke University School of Medicine and chair of the data review committee of the ERADICATE study, added: “There is a high medical need in Staphylococcus aureus bacteremia, therefore, the first approval of a therapy for this indication in over 15 years is highly welcome.”

Adesh Kaul, Chief Financial Officer of Basilea, added: “As we were moving towards completion of the regulatory review, especially with increasing visibility on the expected label, the external interest for commercial partnering increased. Whilst our initial goal was to have announced a commercial partnership by the time of approval of Zevtera in the US, in order to explore fully all potential partnering opportunities, we now expect to complete the process around mid-year. In parallel, we are also taking preparatory steps to shorten the launch timelines, once we have entered into a commercialization partnership.”

Basilea’s phase 3 program for ceftobiprole is funded in part with federal funds from the US Department of Health and Human Services (HHS); Administration for Strategic Preparedness and Response (ASPR); Biomedical Advanced Research and Development Authority (BARDA), under contract number HHSO100201600002C. Through this partnership, Basilea has been awarded approximately USD 112 million, or approximately 75 percent of the costs related to the SAB and ABSSSI phase 3 studies, regulatory activities and non-clinical work.

About Zevtera® (ceftobiprole medocaril sodium for injection)

Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced generation cephalosporin antibiotic for intravenous administration, with rapid bactericidal activity against a wide range of Gram-positive bacteria, such as Staphylococcus aureus, including methicillin-resistant strains (MRSA), and Gram-negative bacteria.4 In several countries in Europe and beyond, the brand is currently approved and marketed as Zevtera® and Mabelio® for the treatment of adult patients with hospital-acquired bacterial pneumonia (HABP), excluding ventilator-associated bacterial pneumonia (VABP), and for the treatment of community-acquired bacterial pneumonia (CABP). Basilea has entered into license and distribution agreements covering more than 80 countries. In the United States, Zevtera is indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including right-sided infective endocarditis, and adult patients with acute bacterial skin and skin structure infections (ABSSSI) and for adult and pediatric patients (3 months to less than 18 years old) with community-acquired bacterial pneumonia (CABP).

Ref: https://en.wikipedia.org/wiki/Ceftobiprole

FDA Approves Zevtera (ceftobiprole medocaril sodium) for Bacteremia, Skin and Skin Structure Infections, and Pneumonia

FDA Approves Zerbaxa (ceftolozane and tazobactam) 3g Dose for the Treatment of Adults with Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP)

      

         Ceftolozane/tazobactam                                                           Tazobactam                                                

Merck (NYSE:MRK), known as MSD outside the United States and Canada, announced that the U.S. Food and Drug Administration (FDA) has approved Merck’s supplemental New Drug Application (sNDA) for the use of Zerbaxa (ceftolozane and tazobactam) for the treatment of patients 18 years and older with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by the following susceptible Gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens. The sNDA for Zerbaxa had previously been designated Priority Review status by the FDA. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Zerbaxa and other antibacterial drugs, Zerbaxa should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

This expanded use is based on results of the pivotal Phase 3 ASPECT-NP trial that compared Zerbaxa 3g (ceftolozane 2g and tazobactam 1g) intravenously every 8 hours to meropenem (1g intravenously every 8 hours) for 8 to 14 days for the treatment of adult patients with HABP/VABP.

Zerbaxa is contraindicated in patients with known serious hypersensitivity to the components of Zerbaxa (ceftolozane/tazobactam), piperacillin/tazobactam, or other members of the beta-lactam class. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials. Additionally, Clostridium difficile-associated diarrhea (CDAD), ranging from mild diarrhea to fatal colitis, has been reported with nearly all systemic antibacterial agents, including Zerbaxa. See Important Safety Information below.

“Pneumonia in ventilated patients remains a significant clinical challenge and is associated with substantial morbidity and mortality,” said Dr. Andrew Shorr, head of pulmonary, critical care and respiratory services, Medstar Washington Hospital Center, Washington, D.C. “The need to cover diverse pathogens including Pseudomonas aeruginosa and certain Enterobacteriaceae adds to the challenge.”

According to a recent publication by the Foundation for the National Institutes of Health Biomarkers Consortium, ventilated patients with HABP have a higher rate of mortality (39%) than those with VABP (27%). In addition, Pseudomonas aeruginosa is the most common Gram-negative pathogen in HABP/VABP and is becoming increasingly difficult to treat.

“We are grateful to all of the patients who participated in the studies which led to the approval of Zerbaxa for the treatment of HABP/VABP,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “This approval reflects Merck’s longstanding commitment to helping alleviate the burden of infectious diseases, including serious infections caused by Gram-negative pathogens.”

Clinical Data Supporting Use of Zerbaxa (Ceftolozane and Tazobactam) in HABP/VABP

A total of 726 adult patients hospitalized with HABP/VABP were enrolled in a multinational, double-blind study (NCT 02070757) comparing Zerbaxa 3g (ceftolozane 2g and tazobactam 1g) intravenously every 8 hours to meropenem (1g intravenously every 8 hours) for 8 to 14 days of therapy. All patients had to be intubated and on mechanical ventilation at randomization.

Efficacy was assessed based on all-cause mortality at Day 28 and clinical cure, defined as complete resolution or significant improvement in signs and symptoms of the index infection at the test-of-cure (TOC) visit which occurred 7 to 14 days after the end of treatment. The analysis population was the intent-to-treat (ITT) population, which included all randomized patients.

Of the 726 patients in the ITT population, the median age was 62 years and 44% of the population was greater than or equal to 65 years of age, with 22% of the population greater than or equal to 75 years of age. The majority of patients were white (83%), male (71%) and were from Eastern Europe (64%). The median APACHE II score was 17 and 33% of patients had a baseline APACHE II score of greater than or equal to 20. All patients were on mechanical ventilation and 519 (71%) had VABP. At randomization, the majority of patients had been hospitalized for greater than or equal to 5 days (77%) and were in an ICU (92%), with 49% of patients ventilated for greater than or equal to 5 days. At baseline, 36% of patients had creatinine clearance (CrCl) less than 80 mL/min. Of these, 14% had CrCl less than 50 mL/min.

Approximately 13% of patients were failing their current antibacterial drug therapy for HABP/VABP, and bacteremia was present at baseline in 15% of patients. Key comorbidities included diabetes mellitus, congestive heart failure, and chronic obstructive pulmonary disease at rates of 22%, 16% and 12%, respectively.

Zerbaxa (ceftolozane and tazobactam) was non-inferior to meropenem for 28-day all-cause mortality in the ITT population (all randomized patients), 24.0% (87/362) and 25.3% (92/364) respectively, for a weighted proportion difference of 1.1 (stratified 95% CI: -5.13, 7.39; non-inferiority margin of 10%). In addition, Zerbaxa was non-inferior to meropenem for clinical response at Test-of-Cure (7-14 days after the end of therapy) in the ITT population, 54.4% (197/362) and 53.3% (194/364) respectively, for a weighted proportion difference of 1.1 (stratified 95% CI: -6.17, 8.29; non-inferiority margin of 12.5%).

In the ventilated HABP sub-group, a favorable response for Zerbaxa in 28-day all-cause mortality was observed, 24.2% (24/99) for Zerbaxa and 37.0% (40/108) for meropenem, respectively, for a weighted proportion difference of 12.8 (stratified 95% CI: 0.18, 24.75). In the VABP subgroup, 28-day all-cause mortality was 24.0% (63/263) for Zerbaxa and 20.3% (52/256) for meropenem, for a weighted proportion difference of -3.6 (stratified 95% CI: -10.74, 3.52).

Adverse reactions occurring in 2% or greater of patients receiving Zerbaxa in this study include hepatic transaminase increased 11.9% (43/361), renal impairment/renal failure 8.9% (32/361), diarrhea 6.4% (23/361), intracranial hemorrhage 4.4% (16/361), vomiting 3.3% (12/361), and Clostridium difficile colitis 2.8% (10/361). Treatment discontinuation due to adverse reactions occurred in 1.1% (4/361) of patients receiving Zerbaxa and 1.4% (5/359) of patients receiving meropenem.

FDA Approves Zerbaxa (ceftolozane and tazobactam) 3g Dose for the Treatment of Adults with 

Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP)

New antibody shows promise in increasing survival for patients suffering from influenza, pneumonia

Scientists from NTU Singapore, the world's No. 1 young university, have developed an antibody which boosts the survival chances for patients suffering from influenza and pneumonia.

Proven effective in lab tests, the antibody is now being made suitable for use in humans. The scientists are also using the new antibody to develop a diagnostic kit which can help doctors accurately track the recovery progress of flu and pneumonia patients.

The patent-pending antibody has generated much interest globally. Two biotech multi-national corporations, Abcam based in the United Kingdom and Adipogen International based in the United States, have won the rights to license the antibody. The two multinational companies will produce the antibody for sale to global organisations doing research in vaccine and drug development.

The breakthrough finding was published in the latest issue of the prestigious international peer-reviewed journal Cell Reports.

Ref : http://www.cell.com/cell-reports/abstract/S2211-1247(15)00024-8

New antibody shows promise in increasing survival for patients suffering from influenza, pneumonia

New Antibiotic Xenleta Approved for Community-Acquired Bacterial Pneumonia

Xenleta (lefamulin) has been approved to treat adults with community-acquired bacterial pneumonia, the U.S. Food and Drug Administration announced today.

Dosing of Xenleta is either an oral administration of 600 mg every 12 hours or an intravenous administration of 150 mg every 12 hours for five to seven days. Patients can be started on either intravenous or oral therapy or can transition from intravenous to oral therapy to accelerate hospital discharge.

Approval was based on data from two clinical trials of 1,289 patients with community-acquired bacterial pneumonia comparing Xenleta taken orally or intravenously to treatment with moxifloxacin with or without linezolid. Clinical success rates of patients treated with Xenleta were similar to those of patients treated with moxifloxacin with or without linezolid.

The most commonly reported adverse reactions with Xenleta include diarrhea, nausea, injection site reactions, elevated liver enzymes, and vomiting. The FDA notes that Xenleta can cause a prolonged QT interval, so patients with arrythmias, those taking antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval should avoid Xenleta. Patients with known hypersensitivity to lefamulin, other members of the pleuromutilin antibiotic class, or any components of Xenleta are also contraindicated. Health care providers should advise pregnant women and those who could become pregnant of the risk for fetal harm with Xenleta as shown in animal studies. Women who could become pregnant should use effective contraception during and two days after taking Xenleta.

Approval of Xenleta was granted to Nabriva Therapeutics. The drug is expected to be available in mid-September with a wholesale acquisition price of $205 per IV patient treatment day and $275 per oral patient treatment day.

https://en.wikipedia.org/wiki/Lefamulin

Allergan Announces FDA Approval of Avycaz (ceftazidime and avibactam) for Pediatric Patients

Allergan plc (NYSE: AGN) announced that the U.S. Food and Drug Administration (FDA) has approved the company's supplemental New Drug Application (sNDA) for Avycaz (ceftazidime and avibactam), expanding the label to include pediatric patients 3 months and older for the treatment of complicated intra-abdominal infections (cIAI) in combination with metronidazole and complicated urinary tract infections (cUTI). This is the first FDA approval of a pediatric indication for cUTI and cIAI in more than a decade.

      

"Difficult-to-treat gram-negative pathogens pose a significant health risk, particularly to the vulnerable and sensitive pediatric patient population with few options for treatment," said David Nicholson, Chief Research & Development Officer at Allergan.  "As resistance rises among the gram-negative pathogens that cause these serious infections, the expanded label for Avycaz provides a safe and effective treatment option now for pediatric patients with cIAI and cUTI. These expanded indications in pediatric patients with infections, including infants and those at a particularly young age, address an unmet need among this vulnerable population and  underscore Allergan's efforts in anti-infective research."

The label expansion was approved based on results from two active-controlled clinical studies evaluating Avycaz in children or infants with cIAI or cUTI, as well as a single-dose pharmacokinetic study. In the cIAI study, the safety and efficacy of Avycaz (in combination with metronidazole) was compared with meropenem. In the cUTI study, Avycaz was compared with cefepime.

Across the trials, 128 pediatric patients 3 months to less than 18 years of age were treated with Avycaz. Overall, the findings from the pediatric studies were similar to the previous determination of safety for Avycaz for the treatment of adult patients with cIAI or cUTI, and no new safety concerns were identified in pediatric patients.

The primary objectives of the studies were to evaluate the safety and tolerability of Avycaz, and they were not powered for a statistical analysis of efficacy. The descriptive efficacy analyses in the pediatric studies were consistent with data from studies in adults with cIAI and cUTI. In the pediatric cIAI study, the clinical cure rate at the test-of-cure (TOC) visit in the intent-to-treat (ITT) population was 91.8% (56/61) in the Avycaz plus metronidazole group and 95.5% (21/22) in the meropenem group. Clinical cure rates for the predominant pathogens, Escherichia coli and Pseudomonas aeruginosa, were 90.5% and 85.7%, respectively for patients treated with Avycaz plus metronidazole, and 92.3% and 88.9%, respectively, for patients treated with meropenem. In the pediatric cUTI study, the combined favorable clinical and microbiological response rate at TOC in the microbiological-ITT population was 72.2% (39/54) in the Avycaz group and 60.9% (14/23) in the cefepime group. The microbiologic response rate for E.coli, the most common uropathogen identified in the study, was 79.6% for patients treated with Avycaz and 59.1% for patients treated with cefepime.

Avycaz was first approved by the FDA in February 2015 for the treatment of cUTI including pyelonephritis, and cIAI in combination with metronidazole, caused by designated susceptible bacteria including certain Enterobacteriaceae and P. aeruginosa, for patients 18 years of age and older. Avycaz was subsequently approved for the treatment of adults with hospital-acquired pneumonia / ventilator-associated pneumonia (HABP/VABP) caused by designated susceptible bacteria in February 2018.

About Avycaz (ceftazidime and avibactam)

Avycaz is a fixed-dose combination antibacterial indicated for the treatment of cIAI (in combination with metronidazole), and cUTI caused by designated susceptible Gram-negative microorganisms in patients 3 months or older. Avycaz is also indicated for the treatment  of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults. Avycaz consists of a combination of avibactam and ceftazidime.

Avibactam is a first-in-class non-beta-lactam beta-lactamase inhibitor which protects ceftazidime against degradation by certain beta-lactamases. Avibactam does not decrease the activity of ceftazidime against ceftazidime-susceptible organisms. Ceftazadime is a third-generation cephalosporin with a well-established efficacy and safety profile.

Avycaz has demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPCs), AmpC and certain oxacillinases (OXA). Avycaz also demonstrated in vitro activity against P. aeruginosa in the presence of some AmpC beta-lactamases, and certain strains lacking outer membrane porin (OprD). Avycaz is not active against bacteria that produce metallo-beta lactamases and may not have activity against Gram-negative bacteria that overexpress efflux pumps or have porin mutations.

Ceftazidime and avibactam is being jointly developed with Pfizer. Allergan holds the rights to commercialize ceftazidime and avibactam in North America under the brand name Avycaz, while Pfizer holds the rights to commercialize the combination in the rest of the world under the brand 

Ref : https://www.drugbank.ca/drugs/DB00438

https://en.wikipedia.org/wiki/Ceftazidime

https://en.wikipedia.org/wiki/Avibactam

https://pubchem.ncbi.nlm.nih.gov/compound/Avibactam#section=2D-Structure

Scientists develop new drug for life-threatening lung disease treatment

Researchers are developing a new drug to treat life-threatening lung damage and breathing problems in people with severe infections like pneumonia, those undergoing certain cancer treatments and premature infants with underdeveloped, injury prone lungs.

Scientists at Cincinnati Children's Hospital Medical Center report April 19 in Science Signaling that a transcription factor called FOXF1 activates several biological processes that promote recovery from acute lung injury. Two laboratories at Cincinnati Children's are developing a pharmacologic compound that in mouse models stimulates FOXF1 and promotes repair after lung injury.

"Besides toxic insults from some cancer treatments, acute lung injury can be a major medical problem for people who get infectious diseases like flu, pneumonia or Ebola because of pathogens that target the lung," said Vladimir Kalinichenko, MD, PhD, co-senior author and a physician and researcher in the Divisions of Pulmonary Biology and Developmental Biology at Cincinnati Children's. "A small molecule compound we developed efficiently stabilizes the FOXF1 protein in cell cultures and mouse lungs, and it shows promise in inhibiting lung inflammation and protecting experimental mice from lung injury."

Along with co-senior author Tanya Kalin, MD, PhD, in the Cincinnati Children's Perinatal Institute, the research team learned that loss of FOXF1 in lung endothelial cells of mice caused them to die from respiratory problems, pulmonary edema (fluid in the lungs) and lung inflammation. This happens when endothelial cells that line blood vessels in the lung can no longer provide a protective barrier between the external environment and the body's circulatory system.

Pentamidine for muscle-wasting-disease.....

Pentamidine (salt of isethionate) is an antimicrobial medication primarily given for prevention and treatment of Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii, also formerly known as Pneumocystis carinii pneumonia (PCP), a severe interstitial type of pneumonia often seen in patients with HIV infection. PCP is considered an 'opportunistic infection', endangering only immunodeficient patients such as those with HIV/AIDS. Pentamidine is also used as a prophylactic in patients receiving chemotherapy, as they also have a depressed immune system as a direct side-effect of the drugs used. The mortality of untreated PCP is very high. Additionally, pentamidine has good clinical activity in treating leishmaniasis, sleeping sickness caused by different strains of Trypanosoma, and yeast infections caused by the organism Candida albicans. Pentamidine is also used as a prophylactic antibiotic for children undergoing treatment for leukemia.

Apart from these diverse applications Pentamidine, has been recently found to become a new therapy for an inherited muscular wasting disease, according to researchers at the University of Oregon and the University of Rochester School of Medicine and Dentistry in New
York.

Pentamidine, when tested in genetically altered mice, counters genetic splicing defects in RNA that lead to type 1 myotonic dystrophy - one of nine types of muscular dystrophy -- also known as DM1 and Steinart's disease. Researchers found that pentamidine disrupted the complexes formed by the expanded repeats and the MBNL protein that becomes stuck to them, allowing the protein to return to its proper location in the cell. The compound also inhibited interactions of MBNL with the cytosine-uracil-guanine repeats and partially rescued two splicing errors in the mice. Though further study like testing with patients suffering from DM1 is still to be established, its a good achievement.

Source : http://uonews.uoregon.edu/archive/news-release/2009/11/possible-help-fight-against-muscle-wasting-disease

New Drug May Fight Serious Respiratory Virus in Infants

 An experimental drug shows promise in treating respiratory syncytial virus (RSV), a leading cause of pneumonia in infants, researchers report.

"We are finally making major progress in being able to treat human RSV infections -- the world's second leading cause of serious viral pneumonia, second only to influenza virus," said study author Dr. John DeVincenzo, a professor of pediatrics at the University of Tennessee College of Medicine in Memphis.

"There is no current treatment or vaccine for RSV pneumonia, and so patients were previously forced to get over the virus by themselves," he said. RSV is the leading cause of hospitalization among infants in the United States, the researchers noted.

In this small study of 140 adults, the drug, dubbed GS-5806, reduced the amount of the virus in the systems of those who received the medication.

"For the first time, we showed that once we reduce the amount of virus in patients, they very quickly started to feel better," DeVincenzo said.

New Drug May Fight Serious Respiratory Virus in Infants  

FDA Approves Vibativ for Hospitalized Patients with Bacterial Pneumonia

We know that, Telavancin (trade name Vibativ) is a bactericidal lipoglycopeptide for use in MRSA or other Gram-positive infections. Telavancin is a semi-synthetic derivative of vancomycin. The FDA approved the drug in September 2009 for complicated skin and skin structure infections (cSSSI)...

Now U.S. Food and Drug Administration today expanded the approved use of the antibiotic Vibativ (telavancin) to treat patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by Staphylococcus aureus. Vibativ should be used for the treatment of HABP/VABP only when alternative treatments are not suitable...

FDA Approves Vibativ for Hospitalized Patients with Bacterial Pneumonia

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 Approves Brukinsa (zanubrutinib) for the Treatment of Mantle Cell Lymphoma

BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer,  announced that Brukinsa (zanubrutinib) has received accelerated approval from the United States Food and Drug Administration (FDA) as a treatment for mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy. Brukinsa is the first BeiGene-discovered product to be approved, an important milestone toward the company’s goal of transforming treatment for cancer patients around the world. 

This accelerated approval is based on overall response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

“We are working to improve outcomes for people with cancer worldwide and this approval brings us closer to realizing our mission of bringing the highest quality therapies to patients globally,” said John V. Oyler, Chairman, Co-Founder, and CEO of BeiGene. “Today’s FDA approval of Brukinsa, following the previously granted Breakthrough Therapy designation in this indication, validates it as an important treatment option for people with relapsed or refractory MCL. We hope this is the first of many approvals for Brukinsa as we continue to evaluate its potential in other hematologic cancers.”
“Brukinsa is a BTK inhibitor that was designed to maximize target occupancy and minimize off-target binding. It entered the clinic in 2014 and since that time our broad development program has enrolled more than 1,600 patients globally,” said Jane Huang, M.D., Chief Medical Officer, Hematology at BeiGene. “Today’s accelerated approval is the culmination of many years of effort by the BeiGene team, the dedicated investigators involved in these trials and, most importantly, the patients who participated by enrolling in the clinical trials. We are humbled by the opportunity to develop this therapy and launch it as our first internally discovered and approved cancer treatment.”

“BTK inhibition is an established mode of treatment for patients with MCL, but many patients treated with previously approved BTK inhibitors do not fully respond to BTK therapy or are forced to discontinue treatment early due to side effects. Today we have a new option for our adult patients who have received one prior systemic or targeted therapy and are living with MCL, an aggressive blood cancer that’s often diagnosed at a more advanced stage,” said Luhua (Michael) Wang, M.D., Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, and clinical trial investigator.
“The approval of Brukinsa as a second line therapy represents an important advancement for the treatment of mantle cell lymphoma,” said Meghan Gutierrez, Chief Executive Officer for the Lymphoma Research Foundation. “Expanded treatment options can transform the patient experience and provide hope to people living with a mantle cell diagnosis.”
The FDA’s approval of Brukinsa is based on efficacy results from two single-arm clinical trials, with independent review committee (IRC)-assessed ORR per 2014 Lugano Classification as the primary endpoint. Across both trials, Brukinsa achieved an ORR, which is the sum of complete responses and partial responses, of 84%.

In the multicenter Phase 2 trial of zanubrutinib in patients with relapsed or refractory (R/R) MCL BGB-3111-206 (NCT03206970), the ORR was 84% (95% CI: 74%, 91%), including 59% complete response (FDG-PET scan required) and 24% partial response. In this study, the median duration of response (DOR) was 19.5 months (95%CI: 16.6, NE) and median follow-up time on study was 18.4 months. In the global Phase 1/2 trial BGB-3111-AU-003  (NCT02343120), the ORR was 84% (95% CI: 67%, 95%), including 22% complete response (FDG-PET scan not required) and 62% partial response. In this study, the median DOR was 18.5 months1 (95% CI:12.6, NE) and median follow-up time on study was 18.8 months.

The most common adverse reactions (> 10%) with Brukinsa were decreased neutrophil count, decreased platelet count, upper respiratory tract infection, decreased white blood cell count, decreased hemoglobin, rash, bruising, diarrhea, cough, musculoskeletal pain, pneumonia, urinary tract infection, blood in the urine (hematuria), fatigue, constipation, and hemorrhage. The most frequent serious adverse reactions were pneumonia (11%) and hemorrhage (5%).

Of the 118 patients with MCL treated with Brukinsa, eight (7%) patients discontinued treatment due to adverse reactions in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) patient experienced an adverse reaction leading to dose reduction (hepatitis B).

The recommended dose of Brukinsa is 320 mg, taken orally 160 mg twice daily or 320 mg once daily with or without food. The dose may be adjusted for adverse reactions, and reduced for patients with severe hepatic impairment and certain drug interactions.

https://en.wikipedia.org/wiki/Zanubrutinib

FDA Approves Brukinsa (zanubrutinib) for the Treatment of Mantle Cell Lymphoma

BeiGene, Ltd.,  a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer,  announced that Brukinsa (zanubrutinib) has received accelerated approval from the United States Food and Drug Administration (FDA) as a treatment for mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy. Brukinsa is the first BeiGene-discovered product to be approved, an important milestone toward the company’s goal of transforming treatment for cancer patients around the world. 

This accelerated approval is based on overall response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

“We are working to improve outcomes for people with cancer worldwide and this approval brings us closer to realizing our mission of bringing the highest quality therapies to patients globally,” said John V. Oyler, Chairman, Co-Founder, and CEO of BeiGene. “Today’s FDA approval of Brukinsa, following the previously granted Breakthrough Therapy designation in this indication, validates it as an important treatment option for people with relapsed or refractory MCL. We hope this is the first of many approvals for Brukinsa as we continue to evaluate its potential in other hematologic cancers.”

“Brukinsa is a BTK inhibitor that was designed to maximize target occupancy and minimize off-target binding. It entered the clinic in 2014 and since that time our broad development program has enrolled more than 1,600 patients globally,” said Jane Huang, M.D., Chief Medical Officer, Hematology at BeiGene. “Today’s accelerated approval is the culmination of many years of effort by the BeiGene team, the dedicated investigators involved in these trials and, most importantly, the patients who participated by enrolling in the clinical trials. We are humbled by the opportunity to develop this therapy and launch it as our first internally discovered and approved cancer treatment.”

“BTK inhibition is an established mode of treatment for patients with MCL, but many patients treated with previously approved BTK inhibitors do not fully respond to BTK therapy or are forced to discontinue treatment early due to side effects. Today we have a new option for our adult patients who have received one prior systemic or targeted therapy and are living with MCL, an aggressive blood cancer that’s often diagnosed at a more advanced stage,” said Luhua (Michael) Wang, M.D., Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, and clinical trial investigator.

“The approval of Brukinsa as a second line therapy represents an important advancement for the treatment of mantle cell lymphoma,” said Meghan Gutierrez, Chief Executive Officer for the Lymphoma Research Foundation. “Expanded treatment options can transform the patient experience and provide hope to people living with a mantle cell diagnosis.”

The FDA’s approval of Brukinsa is based on efficacy results from two single-arm clinical trials, with independent review committee (IRC)-assessed ORR per 2014 Lugano Classification as the primary endpoint. Across both trials, Brukinsa achieved an ORR, which is the sum of complete responses and partial responses, of 84%.

In the multicenter Phase 2 trial of zanubrutinib in patients with relapsed or refractory (R/R) MCL BGB-3111-206 (NCT03206970), the ORR was 84% (95% CI: 74%, 91%), including 59% complete response (FDG-PET scan required) and 24% partial response. In this study, the median duration of response (DOR) was 19.5 months (95%CI: 16.6, NE) and median follow-up time on study was 18.4 months. In the global Phase 1/2 trial BGB-3111-AU-003  (NCT02343120), the ORR was 84% (95% CI: 67%, 95%), including 22% complete response (FDG-PET scan not required) and 62% partial response. In this study, the median DOR was 18.5 months1 (95% CI:12.6, NE) and median follow-up time on study was 18.8 months.

The most common adverse reactions (> 10%) with Brukinsa were decreased neutrophil count, decreased platelet count, upper respiratory tract infection, decreased white blood cell count, decreased hemoglobin, rash, bruising, diarrhea, cough, musculoskeletal pain, pneumonia, urinary tract infection, blood in the urine (hematuria), fatigue, constipation, and hemorrhage. The most frequent serious adverse reactions were pneumonia (11%) and hemorrhage (5%).

Of the 118 patients with MCL treated with Brukinsa, eight (7%) patients discontinued treatment due to adverse reactions in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) patient experienced an adverse reaction leading to dose reduction (hepatitis B).

https://en.wikipedia.org/wiki/Zanubrutinib