Eton Pharmaceuticals Announces FDA Acceptance of New Drug Application for ET-105

In continuation of my update on  lamotrigine

Eton Pharmaceuticals, Inc (Nasdaq: ETON), a specialty pharmaceutical company focused on developing and commercializing innovative drug products, today announced that Aucta Pharmaceuticals' New Drug Application for ET-105, an innovative formulation of lamotrigine which Eton acquired the U.S. marketing rights to in June 2019, has been accepted for review by the U.S. Food and Drug Administration (FDA). The FDA has assigned the application a Prescription Drug User Fee Act (PDUFA) target action date of March 17, 2020.

“The NDA acceptance of ET-105 marks an important milestone for Eton as this strengthens our growing pipeline of near-launch products. We are very excited about the potential for ET-105 to address a significant unmet need in this large and growing market,” said Sean Brynjelsen, Chief Executive Officer of Eton Pharmaceuticals. “Our team looks forward to working with Aucta and the FDA over the coming months as we prepare for a potential commercial launch in the first half of 2020.”

ET-105 is a patent-pending formulation of lamotrigine, for which Aucta is seeking approval as an adjunct therapy for partial seizures, primary generalized tonic-clonic seizures, and generalized seizures of Lennox-Gastaut syndrome in patients two years of age and older. Lamotrigine is one of the most widely used anti-epilepsy medications in the U.S. with sales exceeding $700 million and 1 billion tablets annually but is only FDA-approved in tablet formulations. ET-105’s innovative formula will be delivered to patients as an oral liquid and has been developed specifically to address the significant unmet need in patients with dysphagia and pediatric patients requiring precision dosing at levels below the currently available tablet strengths.

AbbVie's HIV Drug Aluvia (Lopinavir/ritonavir) Seen as Potential Treatment for Coronavirus

In continuation of my update on Lopinavir/Fritonavior

 

More than 80 people have died from the coronavirus in China. The Chinese government is turning to a drug developed by AbbVie for HIV patients as a potential treatment for the outbreak that has reached the shores of the United States.

AbbVie said it was donating more than one million dollars’ worth of Aluvia, a combination of lopinavir and ritonavir as an ad-hoc treatment for pneumonia that is associated with the outbreak. The Chinese government suggested last week that taking two lopinavir/ritonavir pills and inhaling a dose of nebulized alpha-interferon twice a day could benefit these patients, Reuters reported. There are more than 2,000 known cases of the coronavirus in China. The illness has caused parts of China to grind to a halt as health officials seek to contain the spread of the virus.

The decision to use AbbVie’s medicine came after a noted respiratory expert at Peking University First Hospital in Beijing said he was given the HIV drugs to fight the virus after he contracted it following a visit to Wuhan, the capital of Hubei province in central China where the virus is thought to have originated. Wan Guangfa came down with the virus after interacting with coronavirus patients. He told China News Week that the HIV treatments worked for him.

The coronavirus family includes the common cold as well as viruses that cause more serious illnesses, such as SARS that spread from China to more than a dozen countries in 2002-03 and killed about 800 people. Also, the virus is similar to Middle Eastern Respiratory Syndrome (MERS), which developed from camels. The virus infects the lungs, and symptoms start with a fever and cough. It can progress to shortness of breath and breathing difficulties leading to pneumonia.

Aluvia is thought to be a potential treatment for the coronavirus due to its ability to block a protease that the virus needs to replicate within the human body. AbbVie’s drug has previously been tested in patients with SARS and MERS, which are similar viruses, Endpoints reported.

Other drugmakers are also responding. Gilead Sciences is looking at its Ebola virus drug remdesivir, an antiviral, as a potential coronavirus treatment, The Motley Fool reported. Moderna also has a treatment for the virus under investigation. The company received a grant from the Coalition for Epidemic Preparedness Innovations to investigate a treatment for the virus. Inovio also received a grant from CEPI to develop a potential vaccine.

https://en.wikipedia.org/wiki/Lopinavir/ritonavir

AbbVie's HIV Drug Aluvia Seen as Potential Treatment for Coronavirus  

FDA Approves Inrebic (fedratinib) for the Treatment of Patients With Myelofibrosis

Celgene Corporation (NASDAQ: CELG)  announced the U.S. Food and Drug Administration (FDA) approval of  Inrebic (fedratinib) for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis.1

“The approval of Inrebic is another important milestone for Celgene and underscores our commitment to people living with blood cancers,” said Jay Backstrom, M.D., M.P.H., Chief Medical Officer for Celgene. “We are excited to provide Inrebic as a new treatment option that may be used in patients with myelofibrosis, including patients previously treated with ruxolitinib.”

“Myelofibrosis can cause patients to suffer in many ways, including experiencing debilitating symptoms,” said Ruben Mesa, M.D., FACP, Director of the Mays Cancer Center at UT Health San Antonio Cancer Center MD Anderson. “There has not been a new treatment approved for this disease in nearly a decade. With Inrebic, physicians and patients now have another option available for myelofibrosis.”

The Inrebic development program consisted of multiple studies (including JAKARTA and JAKARTA2) in 608 patients who received more than one dose (ranging from 30 mg to 800 mg),1 of whom 459 had myelofibrosis,1 including 97 previously treated with ruxolitinib.1 The JAKARTA study evaluated the efficacy and safety of once-daily oral doses of Inrebic compared with placebo in patients with intermediate-2 or high-risk, primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis who were previously untreated with a JAK inhibitor, had enlarged spleens (a condition known as splenomegaly), and had a platelet count of ≥50 x 109/L (median baseline platelet count was 214 x 109/L; 16% <100 x 109/L and 84% ≥100 x 109/L).1,2 In the JAKARTA study, spleen volume was reduced by 35% or greater, when assessed from baseline to the end of cycle 6 (week 24), with a 4-week follow-up scan, in 37% (35 of 96) of patients treated with INREBIC 400 mg versus 1% (1 of 96) of patients who received placebo (p<0.0001).1 INREBIC also improved the Total Symptom Score as measured by the modified Myelofibrosis Symptoms Assessment Form (MFSAF) v2.0 diary2 (night sweats, itching, abdominal discomfort, early satiety, pain under ribs on left side, bone or muscle pain) by 50% or greater when assessed from baseline to the end of cycle 6 in 40% of (36 of 89) patients treated with 400 mg, versus 9% (7 of 81) of patients who received placebo (p<0.0001).1

Inrebic has a Boxed Warning for serious and fatal encephalopathy, including Wernicke’s. Serious encephalopathy was reported in 1.3% (8 of 608) of patients treated with Inrebic in clinical trials and 0.16% (1 of 608) of the cases were fatal. Wernicke’s encephalopathy is a neurologic emergency resulting from thiamine (Vitamin B1) deficiency. Thiamine levels should be assessed in all patients prior to starting Inrebic, periodically during treatment, and as clinically indicated.1 Do not start Inrebic in patients with thiamine deficiency; replete thiamine prior to treatment initiation. If encephalopathy is suspected, immediately discontinue Inrebic and initiate parenteral thiamine. Monitor until symptoms resolve or improve and thiamine levels normalize.

In the JAKARTA study, serious adverse reactions occurred in 21% of patients treated with Inrebic 400 mg once daily (n=96), with the most common (≥2%) being cardiac failure (5%) and anemia (2%).1 Fatal adverse reactions of cardiogenic shock occurred in 1% of patients.1 Permanent discontinuation due to an adverse reaction occurred in 14% of patients. The most frequent reasons for permanent discontinuation in ≥2% of patients receiving Inrebic included cardiac failure (3%), thrombocytopenia, myocardial ischemia, diarrhea, and increased blood creatinine (2% each).1

Dosage interruptions due to an adverse reaction during the randomized treatment period occurred in 21% of patients who received Inrebic. Adverse reactions requiring dosage interruption in >3% of patients who received Inrebic included diarrhea and nausea. Dosage reductions due to an adverse reaction during the randomized treatment period occurred in 19% of patients who received Inrebic. Adverse reactions requiring dosage reduction in >2% of patients who received Inrebic included anemia (6%), diarrhea (3%), vomiting (3%), and thrombocytopenia (2%).

“Inrebic is a much-welcomed new treatment for the myelofibrosis community,” said Ann Brazeau, Chief Executive Officer and Founder, MPN Advocacy and Education International. “This FDA approval marks an important milestone for people living with myelofibrosis as we embark on making greater strides in the diagnosis, understanding and treatment of this disease.”

https://pubchem.ncbi.nlm.nih.gov/compound/Fedratinib

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

FDA Approves Eylea (aflibercept) Injection Prefilled Syringe

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN)  announced the U.S. Food and Drug Administration (FDA)   approval the Chemistry, Manufacturing and Controls (CMC) Prior-Approval Supplement (PAS) for the Eylea (aflibercept) Injection prefilled syringe. The 2 mg, single-dose, sterilized prefilled syringe provides physicians with a new way to administer Eylea that requires fewer preparation steps compared to vials. Market supply of the Eylea prefilled syringe is expected to be available to physicians and patients this year.

"With eight pivotal Phase 3 trials and millions of injections used around the world, Eylea sets a high bar for visual acuity and safety across multiple retinal diseases, including wet age-related macular degeneration and diabetic eye diseases," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron. "This approval may help doctors more conveniently and efficiently deliver Eylea to appropriate patients."

The sterilized prefilled syringe offers the same medicine as the currently available Eylea, in an easier to use and administer presentation.

In the U.S., Eylea is indicated to treat neovascular (wet) age-related macular degeneration (Wet AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME) and diabetic retinopathy (DR).

About Eylea (aflibercept) Injection

Eylea (aflibercept) Injection is a vascular endothelial growth factor (VEGF) inhibitor formulated as an injection for the eye. It is designed to block the growth of new blood vessels and decrease the ability of fluid to pass through blood vessels (vascular permeability) in the eye by blocking VEGF-A and placental growth factor (PLGF), two growth factors involved in angiogenesis. In the U.S., Eylea is the market-leading, FDA-approved anti-VEGF treatment for its approved indications and is supported by a robust body of research that includes eight pivotal Phase 3 trials.

IMPORTANT SAFETY INFORMATION

• Eylea (aflibercept) Injection is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in Eylea.
• Intravitreal injections, including those with Eylea, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering Eylea. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. Intraocular inflammation has been reported with the use of Eylea.
• Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with Eylea. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately.
• There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including Eylea. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with Eylea compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was 3.3% (60 out of 1824) in the Eylea group compared with 3.2% (19 out of 595) in the ranibizumab group. The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with Eylea compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with Eylea compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with Eylea in the first six months of the RVO studies.
• Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with Eylea including endophthalmitis and retinal detachment.
• The most common adverse reactions (≥5%) reported in patients receiving Eylea were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased.

INDICATIONS

Eylea (aflibercept) Injection 2 mg (0.05 mL) is indicated for the treatment of patients with Neovascular (Wet) Age-related Macular Degeneration (AMD), Macular Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), and Diabetic Retinopathy (DR).

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

https://www.eylea.us/

FDA Approves Rinvoq (upadacitinib), an Oral JAK Inhibitor for the Treatment of Moderate to Severe Rheumatoid Arthritis

In continuation of my update on Rinvoq (upadacitinib)

AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has approved Rinvoq (upadacitinib), a 15 mg, once-daily oral Janus kinase (JAK) inhibitor, for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate (MTX-IR).1 Rinvoq is expected to be available in the U.S. in late August 2019.

The FDA approval of Rinvoq is supported by data from the SELECT program, one of the largest registrational Phase 3 programs in RA with approximately 4,400 patients evaluated across all treatment arms in five studies.2-6 The studies include assessments of efficacy, safety and tolerability across a variety of RA patients, including those who failed or were intolerant to biologic disease-modifying anti-rheumatic drugs and who were naïve or inadequate responders to methotrexate. Rinvoq is not indicated for methotrexate-naïve patients.

"Despite the availability of multiple treatment options with varying mechanisms of action, many patients still do not achieve clinical remission or low disease activity—the primary treatment goals for rheumatoid arthritis," said Roy M. Fleischmann, M.D., primary investigator for SELECT-COMPARE and clinical professor at the University of Texas Southwestern Medical Center at Dallas. "With this FDA approval, Rinvoq has the potential to help additional people living with RA achieve remission who have not yet reached this goal."

Across the SELECT Phase 3 studies, Rinvoq met all primary and ranked secondary endpoints. The primary endpoints include:

• In SELECT-EARLY, 52 percent of MTX-naïve patients treated with Rinvoq 15 mg achieved ACR50 vs 28 percent treated with MTX at week 121
• In SELECT-MONOTHERAPY, 68 percent of MTX-IR patients treated with Rinvoq 15 mg achieved ACR20 vs 41 percent treated with continued MTX at week 141
• In SELECT-COMPARE, 71 percent of MTX-IR patients treated with Rinvoq 15 mg plus MTX achieved ACR20 vs 36 percent treated with placebo plus MTX at week 121
• In SELECT-NEXT, 64 percent of csDMARD-IR patients treated with Rinvoq 15 mg plus csDMARDs achieved ACR20 vs 36 percent treated with placebo plus csDMARDs at week 121
• In SELECT-BEYOND, 65 percent of biologic-IR patients treated with Rinvoq 15 mg plus csDMARDs achieved ACR20 vs 28 percent treated with placebo plus csDMARDs at week 121

"The discovery and development of Rinvoq is indicative of AbbVie's long-standing commitment to advancing the science for people living with immune-mediated conditions," said Michael Severino, M.D., vice chairman and president, AbbVie. "Today's FDA approval marks an important milestone in our pursuit to deliver innovative medicines that advance care for people living with rheumatoid arthritis."

Clinical Remission

Patients taking Rinvoq achieved clinical remission, a state characterized by almost no disease activity and symptoms, even without methotrexate.2-3,6 Approximately 30 percent of patients treated with Rinvoq achieved clinical remission (as assessed by DAS28-CRP<2.6) at week 12 in SELECT-COMPARE and week 14 in SELECT-MONOTHERAPY compared to six percent with placebo plus methotrexate and eight percent with methotrexate, respectively.1 In SELECT-EARLY, 36 percent of patients treated with Rinvoq achieved clinical remission (as assessed by DAS28-CRP<2.6) at week 12 compared to 14 percent with methotrexate.1 

Durable remission rates were observed up to week 26. Forty-eight percent of patients treated with Rinvoq alone in SELECT-EARLY and 41 percent of patients treated with Rinvoq plus methotrexate in SELECT-COMPARE achieved clinical remission at weeks 24 and 26, compared to nine percent with placebo plus methotrexate and 18 percent with methotrexate, respectively.1 Analysis at weeks 24 and 26 were not controlled for multiple comparisons.3,10

Radiographic Inhibition

Rinvoq significantly inhibited radiographic progression as measured by the change in modified total Sharp score (mTSS) from baseline compared to methotrexate in SELECT-EARLY (0.14 vs 0.67) and Rinvoq plus methotrexate compared to placebo plus methotrexate in SELECT-COMPARE (0.15 vs 0.78) through weeks 24 and 26, respectively.1 

Safety

The most common side effects associated with Rinvoq include upper respiratory tract infections (common cold, sinus infections), nausea, cough and pyrexia.1 Patients treated with Rinvoq are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include tuberculosis (TB), invasive fungal, bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.1 Lymphoma and other malignancies have been observed in Rinvoq-treated patients.1 Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions.1 Patients treated with RINVOQ also may be at risk for other serious adverse reactions, including gastrointestinal perforations, neutropenia, lymphopenia, anemia, lipid elevations, liver enzyme elevations, and embryo-fetal toxicity.1 

Ease of Use and Access

Designed to help accommodate the physical limitations of people living with RA, the packaging for Rinvoq includes a bottle cap with a wide, easy-to-grip texture and an embedded tool that punctures the foil liner to simplify medication access. This packaging design was awarded the Arthritis Foundation Ease of Use Commendation.

"Rheumatoid arthritis can have a debilitating impact on the lives of those with the chronic disease, including making it difficult to perform everyday tasks," said Cindy McDaniel, senior vice president, consumer health, Arthritis Foundation. "The Arthritis Foundation is committed to recognizing innovation that can help patients living with rheumatoid arthritis and we are proud to recognize AbbVie with our Ease of Use Commendation for the packaging design of Rinvoq."

AbbVie continues to work closely with key stakeholders to support patient access to Rinvoq, including offering a patient support program and a co-pay card that may reduce out-of-pocket costs to $5 per month for eligible, commercially-insured patients. For those with limited or no health insurance, AbbVie offers myAbbVie Assist, a patient assistance program that provides Rinvoq to qualifying patients.

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

https://www.drugbank.ca/drugs/DB15091

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 Rozlytrek (entrectinib) for People With ROS1-Positive, Metastatic Non-Small Cell Lung Cancer and NTRK Gene Fusion-Positive Solid Tumors

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),  announced  the U.S. Food and Drug Administration (FDA) has approval of  Rozlytrek (entrectinib) for the treatment of adults with ROS1-positive, metastatic non-small cell lung cancer (NSCLC). The FDA has also granted accelerated approval to Rozlytrek for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy.

These approvals are based on results from the integrated analysis of the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, and data from the Phase I/II STARTRK-NG study. In the integrated analysis, Rozlytrek was studied in several solid tumor types, including breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers. In ROS1-positive, metastatic NSCLC, Rozlytrek shrank tumors in 78% of people with the disease (overall response rate [ORR]; N=51) and the duration of response (DoR) ranged from 1.8 to 36.8+ months (N=40 out of 51). Rozlytrek also shrank tumors in more than half of people with NTRK gene fusion-positive, locally advanced or metastatic solid tumors (ORR=57%; N=54), and objective responses were observed across 10 tumor types (DoR ranged from 2.8 to 26.0+ months; N=31 out of 54). Objective responses to Rozlytrek were seen in people with central nervous system (CNS) metastases at baseline.

“Rozlytrek’s FDA approval for two rare types of cancer is an important advance for patients, combining a targeted medicine and genomic testing to bring this new treatment option to patients who are waiting,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Rozlytrek is the first FDA-approved treatment that selectively targets both ROS1 and NTRK fusions, and, importantly, has also shown responses in these rare cancer types that have spread to the brain.”

“The identification of actionable biomarkers like ROS1 has brought about significant progress in the treatment of lung cancer. This approval brings further hope to people with this rare type of the disease,” said Janet Freeman-Daily, co-founder of The ROS1ders, a group of patients and caregivers affected by ROS1-positive lung cancer. “Up to 40% of people with ROS1-positive non-small cell lung cancer have tumors that have spread to the brain, so now there is a new treatment option for those patients.”

The most common adverse reactions (≥20 percent) with Rozlytrek were fatigue, constipation, altered sense of taste (dysgeusia), swelling (edema), dizziness, diarrhea, nausea, nervous system disorders (dysesthesia), shortness of breath (dyspnea), muscle pain (myalgia), cognitive impairment, increased weight, cough, vomiting, fever (pyrexia), joint pain (arthralgia) and vision disorders.

The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious or life-threatening disease or condition. The accelerated approval of Rozlytrek for NTRK gene fusion-positive solid tumors is based on tumor response rate and durability of response, and continued approval may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Biomarker testing for ROS1 in NSCLC and NTRK gene fusions across all solid tumors is the only way to identify people who are eligible for treatment with Rozlytrek. Genentech is leveraging its expertise in developing personalized medicines and advanced diagnostics, in conjunction with Foundation Medicine, to help identify people with ROS1 and NTRK gene fusions. Foundation Medicine will submit Foundation®One CDx to the FDA for approval as a companion diagnostic for Rozlytrek. An FDA-approved companion diagnostic for Rozlytrek is not available at this time.

Rozlytrek is now available in the United States for adults and children 12 years of age and older. For those who qualify, Genentech offers patient assistance programs for people prescribed Rozlytrek by their doctor through Genentech Access Solutions. Please contact Genentech Access Solutions at (866) 422-2377 or visit http://www.Genentech-Access.comfor more information.

About the Integrated Analysis

This approval is based on an integrated analysis including data from 51 people with ROS1-positive NSCLC and 54 people with locally advanced or metastatic NTRK gene fusion-positive solid tumors (10 tumor types, >19 histopathologies) from the Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials. This approval is also based on data from the Phase I/II STARTRK-NG study in pediatric patients. The studies enrolled people across 15 countries and more than 150 clinical trial sites. Safety was assessed from an integrated analysis of 355 people across these four trials.

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

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

FDA Approves EluRyng (etonogestrel/ethinyl estradiol vaginal ring), the First Generic NuvaRing

Amneal Pharmaceuticals, Inc. (NYSE: AMRX) (“Amneal” or the “Company”) announced that it has received Abbreviated New Drug Application (ANDA) approval from the U.S. Food and Drug Administration (FDA) for EluRyng™ (etonogestrel/Ethinyl estradiol vaginal ring), the first generic version of NuvaRing®. Amneal has initiated commercialization activities for EluRyng, which is being manufactured internally and launching today.

We are pleased to announce FDA approval of EluRyng, one of 15 new, complex products we expect to launch over the next 18 to 24 months,” said Chirag and Chintu Patel, Co-Chief Executive Officers. “This milestone underscores Amneal’s deep scientific and regulatory capabilities and our ability to overcome significant barriers to entry, including complex formulation development and specialized manufacturing requirements. In addition, EluRyng adds a differentiated, complex dosage form to our portfolio, and bringing this product to market reflects our commitment to improving affordable access to complex drug products. Looking ahead, we remain enthusiastic about the additional high-value opportunities in our pipeline that are designed to improve the lives of patients and drive meaningful growth and value-creation for our shareholders and other stakeholders in 2020 and beyond.”

According to IQVIA™, a leading healthcare data and analytics provider, NuvaRing U.S. annual sales for the 12 months ended October 31, 2019 were approximately $976 million.
About Amneal

Amneal Pharmaceuticals, Inc. (NYSE: AMRX), headquartered in Bridgewater, NJ, is a fully-integrated pharmaceutical company focused on the development, manufacture and distribution of generic and specialty drug products. The Company has manufacturing operations in North America, Asia, and Europe, working together to bring high-quality medicines to patients primarily within the United States.

Amneal has an extensive portfolio of more than 300 generic medicines and is expanding its portfolio to include complex dosage forms, including biosimilars, in a broad range of therapeutic areas. The Company also markets a portfolio of branded pharmaceutical products through its Specialty segment focused principally on the central nervous system and endocrine disorders. For more information, visit www.amneal.com.

https://www.webmd.com/drugs/2/drug-63403/etonogestrel-ethinyl-estradiol-vaginal/details

FDA Approves Nourianz (istradefylline) as an Add-On Drug to Treat Off Episodes in Adults with Parkinson’s Disease

Kyowa Kirin Co., Ltd., (Kyowa Kirin, TYO: 4151) announced the U.S. Food and Drug Administration (FDA) has granted approval for Nourianz (istradefylline) for use as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson’s disease (PD) experiencing “OFF” episodes.

“We are proud that Nourianz is now ready to help adult patients with Parkinson’s disease in the US,” said Tomohiro Sudo, Head of Global Product Management Office of Kyowa Kirin. “We believe that Nourianz could be an important contributor to improve treatment outcomes. We will keep working to bring the product to patients globally.”

“Kyowa Kirin has a commitment to global health and well-being by creating new value through the pursuit of advances in life sciences and technology particularly in oncology, nephrology, immunology, and the central nervous system,” said Tom Stratford, President of Kyowa Kirin USA Holdings, Inc. “Today's FDA approval of Nourianz is an important milestone and provides US patients with a novel non-dopaminergic once-a-day oral treatment option to be used in conjunction with levodopa/carbidopa for Parkinson’s disease.”

“Today’s approval is the culmination of decades of perseverance in exploring the science and clinical effects of istradefylline and inhibition of adenosine A2A receptor signaling in people with Parkinson’s disease,” said Jeffrey S. Humphrey, MD, Chief Development Officer of Kyowa Kirin Pharmaceutical Development, Inc. “In clinical studies, istradefylline, used as adjunctive treatment to levodopa/carbidopa in adult patients with PD experiencing 'OFF' episodes, was associated with a decrease in OFF Time and increase in ON Time without troublesome dyskinesia. We are grateful for the FDA approval and for the many dedicated scientists and patients whose participation in our research programs has resulted in a new treatment option for Parkinson's disease.”

“Istradefylline is an Adenosine A2A receptor antagonist, and is a novel non-dopaminergic pharmacologic approach to treating OFF episodes for people living with PD,” said Dr. Stuart Isaacson, MD, Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida. “Based on data from four clinical studies, istradefylline taken as an adjunct to levodopa significantly improved OFF time and demonstrated a well-tolerated safety profile. Istradefylline represents an important new treatment option for patients with Parkinson's disease who experience 'OFF' episodes.”

The FDA approval of Nourianz is based on findings from randomized, multi-center, double-blind, placebo-controlled trials in patients with PD taking a stable dose of levodopa/carbidopa with or without other PD medications.

The Kyowa Kirin Group companies strive to contribute to the health and well-being of people around the world by creating new value through the pursuit of advances in life sciences and technologies.

Please see Nourianz indication and Important Safety Information below.

Indication

Nourianz (istradefylline) is an adenosine receptor antagonist indicated as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson’s disease (PD) experiencing “off” episodes.

Important Safety Information

Warnings and Precautions

Dyskinesia: Nourianz in combination with levodopa may cause dyskinesia or exacerbate pre-existing dyskinesia. In clinical trials, 1% of patients treated with either Nourianz 20 mg or 40 mg discontinued treatment because of dyskinesia, compared to 0% for placebo.

FDA Approves Katerzia (amlodipine) Oral Suspension for Pediatric Patients 6 Years of Age and Older

In continuation of my update on amlodipine

Azurity Pharmaceuticals, a specialty pharmaceutical company that makes safe, high-quality treatments for patients requiring customized formulations for their care, announced  that the U.S. Food and Drug Administration (FDA) has approved Katerzia (amlodipine) Oral Suspension, 1 mg/mL, the first and only FDA-approved amlodipine oral suspension. Katerzia is indicated for the treatment of hypertension (high blood pressure) in adults and pediatric patients 6 years of age and older and coronary artery disease in adults.

“We are pleased to announce the FDA approval of Katerzia”, said Neal Muni, MD, MSPH, President and Chief Executive Officer of Azurity Pharmaceuticals. “The addition of Katerzia complements our existing pediatric hypertension portfolio and will strengthen the overall offering from Azurity. It is also our first product approval since CutisPharma and Silvergate Pharmaceuticals came together to make Azurity Pharmaceuticals, making this a truly exciting time.”

Katerzia offers a ready-to-use (simply shake) oral suspension for children 6 years of age and older that require or prefer an oral liquid option of amlodipine. Appropriate dosing for children is now simple, safe, and effective, while providing the assurance of quality as an FDA-approved product. Katerzia will be readily available through an extensive network of pharmacies and a qualified mail order service. For additional information on Katerzia, please email media@azurity.com.

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

Turalio (Pexidartinib) Approved to Treat Tenosynovial Giant Cell Tumor

In continuation of my update on pexidartinib 

Turalio (pexidartinib) capsules have been approved to treat adults with symptomatic tenosynovial giant cell tumor (TGCT), the U.S. Food and Drug Administration announced.

The drug was approved for patients with TGCT with severe morbidity or functional limitations that has not improved with surgery. Turalio is only available through the Risk Evaluation and Mitigation Strategy Program.

Approval was based on data from a multicenter international clinical trial of 120 patients. After 25 weeks, patients who received Turalio had a statistically significant improvement in overall response rate (ORR) to an ORR of 38 percent versus no response in patients who received placebo. Fifteen percent of patients had a complete response and 23 percent had a partial response. Among patients followed for a minimum of six months following initial response, 22 of 23 patients maintained their response for six months or longer; all 13 patients who initially responded and were followed for a minimum of 12 months maintained their response for 12 months or longer.

Commonly reported side effects include lactate dehydrogenase, increased aspartate aminotransferase, loss of hair color, increased alanine aminotransferase, and increased cholesterol. Side effects also include neutropenia, increased alkaline phosphatase, decreased lymphocytes, eye edema, decreased hemoglobin, rash, dysgeusia, and decreased phosphate. A Boxed Warning on the prescription information for Turalio warns about the risk for serious and potentially fatal liver injury and advises health care professionals to monitor patients' liver tests before and during treatment and to alter or discontinue use of the drug if liver tests are abnormal.

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

FDA Approves Gadavist (gadobutrol) Contrast Agent for Use in Cardiac MR in Adult Patients with Known or Suspected Coronary Artery Disease

In continuation of my update on Gadavist (gadobutrol)

Bayer announced today the U.S. Food and Drug Administration (FDA) has approved Gadavist (gadobutrol) injection for use in cardiac magnetic resonance (MR) imaging to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD). Gadavist is now the first and only contrast agent FDA approved for use in cardiac MR – an important diagnostic tool for patients with CAD.

"Gadobutrol-enhanced cardiac MR demonstrated efficacy in a large global multicenter clinical trial," said Daniel S. Berman, MD, FACC, Chief of Cardiac Imaging and Nuclear Cardiology at the Cedars-Sinai Heart Institute and the S. Mark Taper Foundation Imaging Center. "The FDA approval is a landmark for making this validated, non-invasive method available to healthcare professionals to evaluate their patients for the most common form of heart disease in the world."

The approval was based on two multinational, non-randomized, blinded-read Phase 3 studies of almost 1,000 adults with suspected or known CAD based on signs and symptoms. Nearly 800 of those patients were evaluated for efficacy. First approved in 2011, cardiac MR is now the fourth FDA approved indication for Gadavist.2

The Society for Cardiovascular Magnetic Resonance recognizes cardiac MR as a non-invasive tool that provides relevant and actionable information to healthcare professionals.3

"We now have an approved contrast agent for use in cardiac MR to assess perfusion and late gadolinium enhancement in less than one hour," said Scott Flamm, MD, MBA, Head of Cardiovascular Imaging, Cleveland Clinic. "A Gadavist-enhanced cardiac MR is a key diagnostic tool, providing additional important clinical information, which can help physicians manage their patients with known or suspected CAD."

A disease that affects approximately 16.5 million Americans, CAD develops when the major blood vessels that supply the heart with blood, oxygen and nutrients (coronary arteries) become damaged or diseased.1,5 Cholesterol-containing deposits (plaque) in the arteries and inflammation are usually the cause of CAD. When plaque builds up, it narrows the coronary arteries, decreasing blood flow to the heart. Eventually, the decreased blood flow may cause chest pain (angina), shortness of breath, or other coronary artery disease signs and symptoms. A complete blockage can cause a heart attack.4

"This latest FDA approval represents another first from Bayer, as Gadavist is the first and only contrast agent approved for cardiac MR," said Dennis Durmis, SVP and Head of Americas Region at Bayer Radiology. "Not only does this approval add to our existing indications for Gadavist, expanding scientific knowledge, but also underscores our dedication to research and provides radiologists and cardiologists with another diagnostic option as they manage their patients with known or suspected CAD."

About Gadavist

Gadavist (gadobutrol) injection was first approved in the U.S. in 2011 for intravenous use in magnetic resonance (MR) imaging in adults and children (2 years of age and older) to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system. Gadavist was further approved in the U.S. in 2014 for MR of the breast in adult patients to assess the presence and extent of malignant breast disease and for pediatric patients less than 2 years of age, including term neonates, to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system. In 2016, it was approved in the U.S. for use with magnetic resonance angiography (MRA) to evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients including term neonates.

Gadavist, also known as Gadovist® and Gadovist® 1.0 in other regions, is the U.S. brand name of the aqueous 1.0M solution of gadobutrol, a gadolinium (Gd)-based extracellular contrast agent for MRI with a macrocyclic structure. The safety profile of Gadavist has been established in clinical trials involving 7,713 patients (including 184 pediatric patients ages 0-17). The safety and effectiveness of Gadavist have not been established in preterm neonates for any indication or in pediatric patients of any age for use with MR to assess the presence and extent of malignant breast disease, or for use in cardiac MR to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in patients with known or suspected coronary artery disease (CAD). Please see Important Safety Information, including Boxed Warning below.

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