FDA Approves Fetroja (cefiderocol) for the Treatment of Complicated Urinary Tract Infections

The U.S. Food and Drug Administration approved Fetroja (cefiderocol), an antibacterial drug for treatment of patients 18 years of age or older with complicated urinary tract infections (cUTI), including kidney infections caused by susceptible Gram-negative microorganisms, who have limited or no alternative treatment options.

“Today’s approval provides an additional treatment option for patients with cUTIs who have limited or no alternative treatment options,” said John Farley, M.D., M.P.H., acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research. “A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. This approval represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections.”

The safety and effectiveness of Fetroja was demonstrated in a study of 448 patients with cUTIs. Of the patients who were administered Fetroja, 72.6% had resolution of symptoms and eradication of the bacteria approximately seven days after completing treatment, compared with 54.6% in patients who received an alternative antibiotic. The clinical response rates were similar between the two treatment groups.

Labeling for Fetroja includes a warning regarding the higher all-cause mortality rate observed in Fetroja-treated patients compared to those treated with other antibiotics in a trial in critically ill patients with multidrug-resistant Gram-negative bacterial infections. The cause of the increase in mortality has not been established. Some of the deaths were a result of worsening or complications of infection, or underlying co-morbidities. The higher all-cause mortality rate was observed in patients treated for hospital-acquired/ventilator-associated pneumonia (i.e.nosocomial pneumonia), bloodstream infections, or sepsis. The safety and efficacy of Fetroja has not been established for the treatment of these types of infections.

The most common adverse reactions observed in patients treated with Fetroja included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion site reactions, candidiasis (yeast infection), cough, headache and hypokalemia (low potassium). Fetroja should not be used in individuals with a known history of severe hypersensitivity to beta-lactam antibacterial drugs.

Fetroja received the FDA’s Qualified Infectious Disease Product (QIDP) designation. The QIDP designation is given to antibacterial and antifungal drug products intended to treat serious or life-threatening infections under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act. As part of QIDP designation, Fetroja was granted Priority Review under which the FDA’s goal is to take action on an application within an expedited time frame.

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

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

FDA Approves Reblozyl (luspatercept-aamt) for the Treatment of Anemia in Adults With Beta Thalassemia Who Require Regular Red Blood Cell Transfusions

In continuation of my update on Luspatercept 

Celgene Corporation (NASDAQ: CELG) and Acceleron Pharma Inc. (NASDAQ: XLRN) today announced the U.S. Food and Drug Administration (FDA) has approved Reblozyl (luspatercept-aamt) for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions. Reblozyl is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia. Reblozyl is the first and only FDA-approved erythroid maturation agent, representing a new class of therapy which works by regulating late-stage red blood cell maturation to help patients reduce their RBC transfusion burden.

“Today’s approval is an important milestone and underscores our continued commitment to patients with hematology disorders,” said Nadim Ahmed, President, Global Hematology and Oncology for Celgene. “There are very limited options for patients living with anemia due to beta thalassemia who are dependent on long term red blood cell transfusions. We are pleased to make Reblozyl available as a new therapy for these patients to help address their anemia, a significant clinical complication of beta thalassemia.”

“We’re thrilled that Acceleron’s first approved medicine is one with the potential to help patients with beta thalassemia, who have been in need of new treatments for this lifelong disease,” said Habib Dable, President and Chief Executive Officer of Acceleron. “We are enormously grateful to the patients, families and caregivers who participated in and supported our research. Their contributions have been essential in helping to ensure that Reblozyl would emerge successfully from our longstanding collaboration with Celgene.”

Beta thalassemia is a rare, inherited blood disorder caused by a genetic defect in hemoglobin. The disease is associated with ineffective erythropoiesis, which results in the production of fewer and less healthy RBCs, often leading to severe anemia – a condition that can be debilitating and can lead to more severe complications for patients – as well as other serious health issues. Treatment options for anemia associated with beta thalassemia are limited, consisting mainly of RBC transfusions, which have the potential to contribute to iron overload, which can cause serious complications such as organ damage.

The approval of Reblozyl for beta thalassemia, which received a Priority Review designation from the FDA, is based on results from the pivotal, Phase 3, randomized, double-blind, placebo-controlled, multicenter BELIEVE trial evaluating the safety and efficacy of Reblozyl for the treatment of anemia in adult patients with beta thalassemia who require regular RBC transfusions (defined as 6-20 RBC units per 24 weeks, with no transfusion-free period greater than 35 days during that period). All patients were eligible to receive best supportive care, which included RBC transfusions; iron-chelating agents; use of antibiotic, antiviral, and antifungal therapy; and/or nutritional support, as needed. The trial achieved a clinically meaningful and statistically significant improvement in the primary endpoint. In the Reblozyl arm, 21.4% of patients (n=48) achieved a ≥33% reduction from baseline in RBC transfusion burden (with a reduction of at least 2 units) during weeks 13–24 after randomization, compared to 4.5% (n=5) in the placebo arm (risk difference [95% CI]: 17.0 [10.4, 23.6], P<0.0001).

The study also met key secondary endpoints, including transfusion burden reduction of at least 33% (with a reduction of at least 2 units), during weeks 37 to week 48, which was achieved in 19.6% (n=44) of patients in the Reblozyl arm and 3.6% (n=4) in the placebo arm (risk difference [95% CI]: 16.1 [9.8, 22.4], P<0.0001).

Other efficacy endpoints included transfusion burden reduction of ≥50% (with a reduction of at least 2 units) during weeks 13-24 and weeks 37-48.1 A ≥50% reduction in transfusion burden was observed in 7.6% of patients (n=17) receiving Reblozyl vs. 1.8% of patients (n=2) in the placebo arm at weeks 13-24 (risk difference [95% CI]: 5.8 [1.6, 10.1], P=0.0303), and 10.3% of patients (n=23) vs. 0.9% of patients (n=1) at weeks 37-48 (risk difference [95% CI]: 9.4 [5, 13.7], P=0.0017), respectively.

In the BELIEVE trial, thromboembolic events, including deep vein thromboses, pulmonary embolus, portal vein thrombosis, and ischemic stroke, were experienced in 3.6% (8/223) of Reblozyl treated patients.1 Hypertension was reported in 10.7% (61/571) of Reblozyl-treated patients across the clinical development program.1 Reblozyl may cause fetal harm when administered to a pregnant woman. Serious adverse reactions occurred in 3.6% of patients receiving Reblozyl.1 Serious adverse reactions reported in 1% of patients were cerebrovascular accident and deep vein thrombosis.1 One patient died due to an unconfirmed case of AML.1 The most common adverse reactions (at least 10% for Reblozyl, and 1% more than placebo) were headache (26% vs 24%), bone pain (20% vs 8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%).

Permanent discontinuation due to an adverse reaction (Grades 1-4) occurred in 5.4% of patients who received Reblozyl.1 The most frequent adverse reactions requiring permanent discontinuation in patients who received Reblozyl included arthralgia (1%), back pain (1%), bone pain (<1%), and headache (<1%).1 Dosage reductions due to an adverse reaction occurred in 2.7% of patients who received Reblozyl.1 The most frequent adverse reactions requiring a dosage reduction in >0.5% of patients who received Reblozyl included hypertension and headache.1 Dosage interruptions due to an adverse reaction occurred in 15.2% of patients who received Reblozyl.1 The most frequent adverse reactions requiring a dosage interruption in >1% of patients who received Reblozyl included upper respiratory tract infection, ALT increase, and cough.

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

FDA Approves Pretomanid for Highly Drug-Resistant Forms of Tuberculosis

In continuation of my update on Pretomanid

 Pretomanid, a novel compound developed by the non-profit organization TB Alliance, was approved by the U.S. Food & Drug Administration (FDA) today for treating some of the most drug-resistant forms of tuberculosis (TB).1 The new drug was approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD pathway) as part of a three-drug, six-month, all-oral regimen for the treatment of people with extensively drug-resistant TB (XDR-TB) or multidrug-resistant TB (MDR-TB) who are treatment-intolerant or non-responsive (collectively “highly drug-resistant TB”).1,2

The LPAD pathway was established by FDA as a tool to encourage further development of antibacterial and antifungal drugs to treat serious, life-threatening infections that affect a limited population of patients with unmet needs. 

“FDA approval of this treatment represents a victory for the people suffering from these highly drug-resistant forms of the world’s deadliest infectious disease,” said Mel Spigelman, MD, president and CEO of TB Alliance. “The associated novel regimen will hopefully provide a shorter, more easily manageable and highly efficacious treatment for those in need.”

The three-drug regimen consisting of bedaquiline, pretomanid and linezolid – collectively referred to as the BPaL regimen – was studied in the pivotal Nix-TB trial across three sites in South Africa. The trial enrolled 109 people with XDR-TB as well as treatment-intolerant or non-responsive MDR-TB.2

Nix-TB data have demonstrated a successful outcome in 95 of the first 107 patients after six months of treatment with BPaL and six months of post-treatment follow-up.2 For two patients, treatment was extended to nine months. The new drug application contains data on 1,168 people who have received pretomanid in 19 clinical trials that have evaluated the drug’s safety and efficacy.2 Pretomanid has been clinically studied in 14 countries.

TB, in all forms, must be treated with a combination of drugs; the most drug-sensitive forms of TB require six months of treatment using four anti-TB drugs.3 Treatment of XDR-TB or treatment-intolerant/non-responsive MDR-TB has historically been lengthy and complex; most XDR-TB patients currently take a combination of as many as eight antibiotics, some involving daily injections, for 18 months or longer.3,4 Prior to recent introduction of new drugs for drug-resistant TB, the World Health Organization (WHO) has reported estimates for treatment success rates of XDR-TB therapy at approximately 34 percent and about 55 percent for MDR-TB therapy.4

“Until very recently, people infected with highly drug-resistant TB had poor treatment options and a poor prognosis,” said Dr. Francesca Conradie, principal investigator of the Nix-TB trial. “This new regimen provides hope with 9 out of 10 patients achieving culture negative status at 6 months post-treatment  with this short, all-oral regimen."

Pretomanid is a new chemical entity and a member of a class of compounds known as nitroimidazooxazines. TB Alliance acquired the developmental rights to the compound in 2002. It has been developed as an oral tablet formulation for the treatment of TB in combination with bedaquiline and linezolid, two other anti-TB agents, and is now indicated for use in a limited and specific population of patients.1 Adverse reactions reported during the Nix-TB trial of the BPaL regimen include hepatotoxicity, myelosuppression, as well as peripheral and optic neuropathy.1 Please see additional safety information in the Important Safety Information below.

Pretomanid is only the third new anti-TB drug approved for use by FDA in more than 40 years, as well as the first to be developed and registered by a not-for-profit organization.5,6 Pretomanid was granted Priority Review, Qualified Infectious Disease Product, and Orphan Drug status. As a product development partnership, TB Alliance has collaborated with and received significant support from numerous governments, academia, philanthropic institutions, the private sector, civil society organizations and other partners over the course of pretomanid’s development.

Pretomanid is expected to be available in the United States by the end of this year. In addition to the U.S. FDA, TB Alliance has submitted pretomanid as part of the BPaL regimen for review by the European Medicines Agency and has provided data to the World Health Organization for consideration of inclusion in treatment guidelines for highly drug-resistant TB.

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

FDA Approves Talicia (omeprazole magnesium, amoxicillin and rifabutin) for the Treatment of H. pylori Infection in Adults

In continuation of my update on omeprazole and amoxicillin   

RedHill Biopharma Ltd. (Nasdaq: RDHL) (Tel-Aviv Stock Exchange: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company primarily focused on the development and commercialization of proprietary drugs for the treatment of gastrointestinal diseases,  announced that the U.S. Food and Drug Administration (FDA) has approved Talicia (omeprazole magnesium, amoxicillin and rifabutin) delayed-release capsules 10 mg1/250 mg/12.5 mg for the treatment of Helicobacter pylori (H. pylori) infection in adults. RedHill expects to launch Talicia1 in the U.S. in the first quarter of 2020 with its dedicated sales force.

Talicia is the only rifabutin-based therapy approved for the treatment of H. pylori infection and is designed to address the high resistance of H. pylori bacteria to current clarithromycin-based standard-of-care therapies. It is estimated that H. pylori resistance to clarithromycin more than doubled between 2009-2013.

Professor David Y. Graham, MD, MACG, Professor of Medicine, Molecular Virology and Microbiology at Baylor College of Medicine, Houston and Lead Investigator of the Talicia Phase 3 studies, said: “Talicia offers patients a much-needed new treatment option for H. pylori with an excellent safety and efficacy profile that is not compromised by clarithromycin or metronidazole resistance. The clinical studies for Talicia demonstrated high efficacy in eradication of H. pylori. Studies with Talicia found zero resistance to rifabutin and showed 17% resistance to clarithromycin, a current standard-of-care macrolide antibiotic, consistent with current data showing that clarithromycin-containing therapies fail in approximately 25-40% of cases.”

Colin W. Howden, MD, AGAF, FACG, Hyman Professor of Medicine & Chief of the Division of Gastroenterology, University of Tennessee Health Science Center, added: “H. pylori is a major cause of peptic ulcer and gastritis. It is also carcinogenic and is the leading cause of gastric cancer. Treatment of H. pylori infection has become increasingly difficult due to growing bacterial resistance and the lack of advances in treatment options over the past decade. Talicia offers a new effective treatment option to overcome bacterial resistance and provide optimal efficacy and I believe it could become a recommended first-line standard-of-care treatment for H. pylori infection.”

“The FDA’s approval of Talicia demonstrates our unwavering dedication to patients suffering from gastrointestinal diseases. We thank the patients, researchers and clinical staff who participated in the studies of Talicia and the RedHill team and vendors for this important milestone achieved by their commitment and hard work,” said Dror Ben-Asher, Chief Executive Officer of RedHill Biopharma. “We are working to expand our sales force to approximately 140 representatives who will promote Talicia, Aemcolo and other gastrointestinal-focused products in our basket.”

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 Xcopri (cenobamate) for the Treatment of Partial-Onset Seizures in Adults

In continuation of my update on cenobamate

 SK Biopharmaceuticals, Co., Ltd., an innovative global pharmaceutical company focused on developing and bringing treatments to market for central nervous system (CNS) disorders, and its U.S. subsidiary SK Life Science, Inc. announced  that the U.S. Food and Drug Administration (FDA) has approved Xcopri (cenobamate tablets) as a treatment for partial-onset seizures in adults.

"The approval of Xcopri will provide clinicians with an effective medication for our patients who are continuing to have focal (partial-onset) seizures," said Michael Sperling, MD, Professor of Neurology and Director of the Jefferson Comprehensive Epilepsy Center at the Vickie and Jack Farber Institute for Neuroscience – Jefferson Health in Philadelphia, and an investigator in the Xcopri clinical development program. "It is very encouraging to see that patients receiving Xcopri saw significant reductions in frequency of seizures, with some even achieving zero seizures." 

The approval is based on results from two global, randomized, double-blind, placebo-controlled studies and a large, global, multi-center, open-label safety study that enrolled adults with uncontrolled partial-onset seizures, taking one to three concomitant anti-epileptic drug (AEDs). In the randomized studies (Study 013 and Study 017), Xcopri demonstrated significant reductions in seizure frequency compared to placebo at all doses studied.

"Approximately 3 million adults live with epilepsy in the U.S. and according to the Centers for Disease Control and Prevention (CDC), nearly 60% reported having seizures, even if they took an AED," said Beth Lewin Dean, Chief Executive Officer of Citizens United for Research in Epilepsy (CURE). "There is an urgent need to advance research and introduce new treatment options. The FDA approval of Xcopri for the treatment of partial-onset seizures is a welcome option for the epilepsy community."

The approval also marks the first time a Korean company has independently brought a compound from discovery to U.S. FDA approval.

"Today's approval is a major step toward our goal of becoming a fully-integrated global pharmaceutical company that can discover, develop and deliver new treatment options in epilepsy and CNS," said Jeong Woo Cho, PhD, President and CEO of SK Biopharmaceuticals and SK life science. "We are grateful to the thousands of participants in our trials, clinical investigators, partners in the epilepsy community and our employees for their important contributions in bringing forward this treatment option for adults with partial-onset seizures."

In Study 013, which included a 6-week titration phase followed by a 6-week maintenance phase, a statistically significant 56% reduction in median seizure frequency was seen with Xcopri 200 mg/day (n=113) versus a 22% reduction with placebo (n=108). In Study 017, which included a 6-week titration phase followed by a 12-week maintenance phase, patients randomized to Xcopri 100 mg/day (n=108), 200 mg/day (n=109) or 400 mg/day (n=111) had statistically significant 36%, 55% and 55% reductions in median seizure frequency, respectively, versus a 24% reduction with placebo (n=106). During the maintenance phase of Study 013, a post-hoc analysis showed that 28% of patients receiving Xcopri had zero seizures, compared with 9% of placebo patients. During the maintenance phase of Study 017, 4% of patients in the Xcopri 100 mg/day group, 11% of patients in the Xcopri 200 mg/day group, 21% of patients in the Xcopri 400 mg/day group and 1% of patients in the placebo group reported zero seizures.

Serious reactions associated with Xcopri include drug reaction with eosinophilia and systemic symptoms (DRESS), QT shortening, suicidal behavior and ideation, and neurological adverse reactions. The most common (≥10% and greater than with placebo) treatment-emergent adverse events associated with Xcopri include somnolence (sleepiness), dizziness, fatigue, diplopia (double vision) and headache.

Xcopri is expected to be available in the U.S. in the second quarter of 2020, following scheduling review by the DEA, which typically occurs within 90 days of FDA approval. SK life science is committed to supporting patients taking Xcopri and will introduce a new access program to help patients get started and stay on track with their medicine.

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

FDA Approves Xcopri (cenobamate) for the Treatment of Partial-Onset Seizures in Adults

FDA Approves Oxbryta (voxelotor) for the Treatment of Sickle Cell Disease

In continuation of my update on voxelotor

Global Blood Therapeutics, Inc. (GBT) (NASDAQ: GBT) announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Oxbryta (voxelotor) tablets for the treatment of sickle cell disease (SCD) in adults and children 12 years of age and older. Oxbryta, an oral therapy taken once daily, is the first approved treatment that directly inhibits sickle hemoglobin polymerization, the root cause of SCD. The medicine is expected to be available through GBT’s specialty pharmacy partner network within two weeks.

“Today is a major milestone not only for GBT but, most importantly, for people living with SCD, their families and those who care for them. When we started our journey with the SCD community more than eight years ago, we set out to transform the way this devastating, lifelong disease is treated,” said Ted W. Love, M.D., president and chief executive officer of GBT. “We are proud to bring this breakthrough therapy to the SCD community. Uniquely developed from inception to treat SCD, Oxbryta embodies GBT’s commitment to develop and deliver innovative medicines for patients with overlooked, life-limiting chronic diseases. We are grateful to the patients, caregivers, clinical trial investigators, healthcare providers and advocates who have worked alongside us to develop this first-in-class therapy.”

SCD affects an estimated 100,000 people in the United States and millions of people throughout the world, particularly among those whose ancestors are from sub-Saharan Africa. It also affects people of Hispanic, South Asian, Southern European and Middle Eastern ancestry.4 SCD is a lifelong inherited blood disorder that impacts hemoglobin, a protein carried by red blood cells that delivers oxygen to tissues and organs throughout the body.2 Due to a genetic mutation, people with SCD form abnormal hemoglobin known as sickle hemoglobin. Through a process called hemoglobin polymerization, red blood cells become sickled – deoxygenated, crescent-shaped and rigid.2,3,5 The sickling process causes hemolytic anemia (low hemoglobin due to red blood cell destruction) and blockages in capillaries and small blood vessels, which impede the flow of blood and oxygen throughout the body. The diminished oxygen delivery to tissues and organs can lead to life-threatening complications, including stroke and irreversible organ damage.

“Every person with SCD experiences hemoglobin polymerization and suffers from varying severity of anemia and hemolysis,” said Elliott Vichinsky, M.D., director of hematology/oncology at UCSF Benioff Children’s Hospital in Oakland, California. “With today’s approval of Oxbryta, we now have a therapy that significantly improves hemoglobin levels, has a favorable safety profile and reduces the anemia and hemolysis that inevitably leads to the long-term and often undetected detrimental effects associated with this chronic genetic condition.”

The accelerated approval of Oxbryta is based on clinically meaningful and statistically significant improvements in hemoglobin levels, accompanied by reductions in red blood cell destruction (hemolysis). Data from the Phase 3 HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization) Study of 274 patients 12 years of age and older with SCD showed that, after 24 weeks of treatment, 51.1% of patients receiving Oxbryta achieved a greater than 1 g/dL increase in hemoglobin compared with 6.5% receiving placebo (p<0.001). Results from the HOPE Study were published in June 2019 in The New England Journal of Medicine.

The most common adverse reactions occurring in ≥10% of patients treated with Oxbryta with a difference of >3% compared to placebo were headache (26% vs. 22%), diarrhea (20% vs. 10%), abdominal pain (19% vs. 13%), nausea (17% vs. 10%), fatigue (14% vs. 10%), rash (14% vs. 10%) and pyrexia (12% vs. 7%).

“SCD is a devastating, lifelong, inherited blood disorder that greatly impacts a person’s life, including their ability to work, attend school and look after their families, and it can reduce their overall life expectancy,” said Beverley Francis-Gibson, president and CEO of the Sickle Cell Disease Association of America. “After decades of waiting, we now have a treatment option that could change the course of this disease. We look forward to continuing to collaborate with GBT on initiatives aimed at transforming the care of patients living with SCD and ensuring access to important and innovative new medicines.”

GBT is committed to ensuring that people with SCD who are prescribed Oxbryta have help accessing the medicine. The company has established GBT Source™, a comprehensive program for patients who are prescribed Oxbryta that provides a wide range of practical, educational and financial support customized to each patient’s needs. GBT Source provides support by reviewing insurance coverage options and explaining benefits; working with the specialty pharmacy partner network to coordinate delivery of Oxbryta to wherever the patient chooses; helping with financial and co-pay assistance for eligible patients; and helping patients stay on treatment as prescribed by their treating physicians with a nurse support team. More information is available at www.Oxbryta.com or 1-833-428-4968 (1-833-GBT-4YOU).

The FDA instituted its accelerated approval pathway to allow for earlier approval of drugs that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint.9 As a condition of accelerated approval, GBT will continue to study Oxbryta in the HOPE-KIDS 2 Study, a post-approval confirmatory study using transcranial doppler (TCD) flow velocity to demonstrate a decrease in stroke risk in children 2 to 15 years of age. The study will be initiated by the end of the year.

In recognition of the critical need for new SCD treatments, the FDA reviewed Oxbryta under Priority Review and granted Oxbryta Breakthrough Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease designations for the treatment of patients with SCD.

Indication

Oxbryta is a prescription medicine used for the treatment of sickle cell disease in adults and children 12 years of age and older. It is not known if Oxbryta is safe and effective in children below 12 years of age.

This indication is approved under accelerated approval based on increase in hemoglobin (Hb). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

Important Safety Information

Oxbryta should not be taken if the patient has had an allergic reaction to voxelotor or any of the ingredients in Oxbryta. See the end of the patient leaflet for a list of the ingredients in Oxbryta.

Oxbryta can cause serious side effects, including serious allergic reactions. Patients should tell their healthcare provider or get emergency medical help right away if they get rash, hives, shortness of breath or swelling of the face.

Patients receiving exchange transfusions should talk to their healthcare provider about possible difficulties with the interpretation of certain blood tests when taking Oxbryta.

The most common side effects of Oxbryta include headache, diarrhea, stomach (abdominal) pain, nausea, tiredness, rash and fever. These are not all the possible side effects of Oxbryta.

Before taking Oxbryta, patients should tell their healthcare provider about all medical conditions, including if they have liver problems; if they are pregnant or plan to become pregnant as it is not known if Oxbryta can harm an unborn baby; or if they are breastfeeding or plan to breastfeed as it is not known if Oxbryta can pass into breastmilk or if it can harm a baby. Patients should not breastfeed during treatment with Oxbryta and for at least 2 weeks after the last dose.

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Some medicines may affect how Oxbryta works. Oxbryta may also affect how other medicines work.

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

FDA Approves Exservan (riluzole) Oral Film for the Treatment of Amyotrophic Lateral Sclerosis

In continuation of my update on riluzole

Aquestive Therapeutics, Inc. (NASDAQ: AQST), a specialty pharmaceutical company focused on developing and commercializing differentiated products to solve therapeutic problems,  announced that Exservan (riluzole) Oral Film received early-action approval from the U.S. Food and Drug Administration (FDA) for the treatment of amyotrophic lateral sclerosis (ALS), an orphan disease.

We received full FDA approval for Exservan in advance of our PDUFA action date.  We appreciate the ongoing feedback from the FDA and its early-action approval.  We anticipate that Exservan, via our orally administered PharmFilm® dosage form, will bring meaningful treatment to patients who are diagnosed with ALS and face difficulties swallowing or administering traditional forms of medication,” said Keith J. Kendall, Chief Executive Officer of Aquestive.  “In line with our stated objectives, we licensed this product to Zambon S.p.A. for development and commercialization in the EU.  We are continuing the dialogue with potential licensees for the US commercial rights.”

Exservan (riluzole) Oral Film is now approved for the treatment of ALS, a debilitating and rare disease affecting as many as 30,000 Americans1 and 52,000 Europeans.  Exservan will now fill a critical need in the armamentarium for ALS patients because it can be administered safely and easily, twice daily, without water where many patients have trouble swallowing. Development initiatives conducted by Aquestive have included studies demonstrating Exservan's pharmacokinetic bioequivalence to the reference listed drug, Rilutek®, as well as additional studies to assess patients' ability to swallow Exservan. Exservan received FDA orphan drug designation in January 2018.

https://www.rxlist.com/exservan-drug.htm

FDA Approves RediTrex (methotrexate) for Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, and Psoriasis

In continuation of my update on methotrexate

Cumberland Pharmaceuticals Inc. (NASDAQ: CPIX), a specialty pharmaceutical company, today announced that it has received approval from the U.S. Food and Drug Administration (FDA) for RediTrex, its new line of methotrexate products.

RediTrex (methotrexate) injection is designed for the treatment of adult and pediatric patients with rheumatoid arthritis, as well as adults with psoriasis. The approval of the product came after a number of communications with the FDA and several amendments to the New Drug Application we submitted to the FDA in late 2018.

Methotrexate is approved in the U.S. as both an oral and injectable treatment. While oral formulations are widely available, injectable methotrexate has been shown to result in increased efficacy, greater continuation rates and less discomfort for patients. Cumberland's methotrexate products will provide enhancements and patient benefits over conventional injectable methotrexate products currently available in the U.S.

Cumberland has acquired exclusive U.S. commercial rights to Nordic Group B.V.'s (Nordic) injectable methotrexate line of products. Nordic is a privately-owned European pharmaceutical company with a presence in 17 countries. The company focuses on the development and commercialization of niche hospital and orphan products, aiming to address unmet medical needs. Nordic's methotrexate products are established market leaders in multiple European countries.

"We are delighted by the FDA approval of RediTrex for the United States," said A.J. Kazimi, Chief Executive Officer of Cumberland Pharmaceuticals. "We are looking forward to bringing this important product to the patients seeking an easy-to-use methotrexate injectable."

Cumberland will launch two injectable methotrexate product lines within the U.S., with both product offerings intended for the treatment of active rheumatoid arthritis, juvenile idiopathic arthritis and severe psoriasis.

The injectable U.S. methotrexate market totaled over 670,000 prescriptions last year, with approximately $80 million in overall sales. This methotrexate market has grown at a rate of 72 percent over the previous three years. Cumberland's goal is to achieve a significant share of the injectable methotrexate market over time through the introduction of RediTrex.

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

FDA Approves Nouress (cysteine hydrochloride) Injection for Treating Neonate Patients Requiring Total Parenteral Nutrition (TPN)

Avadel Pharmaceuticals plc (Nasdaq: AVDL) announced that the U.S. Food and Drug Administration (FDA) has approved Nouress (AV001), a cysteine hydrochloride injection, a critical drug for treating neonatal patients requiring total parenteral nutrition (TPN).

In addition, Avadel announced today that the United States Patent and Trademark Office (USPTO) recently issued United States Patent No. 10,493,051 covering cysteine solutions, including the approved Nouress product. This patent is listed in the Orange Book for Nouress and is set to expire in March of 2039. Avadel has additional U.S. patent applications pending for Nouress.

“We are pleased to receive FDA approval for Nouress, which validates our strategy of developing innovative medicines for patients,” said Greg Divis, Chief Executive Officer of Avadel. “Nouress is the fourth FDA approved product in our sterile injectable hospital business. The cash flow generated by this legacy business is supporting the clinical development costs from our lead program, FT218, which is currently expected to announce topline data from the pivotal Phase 3 REST-ON trial in the second quarter of 2020. We believe that as a once-nightly formulated sodium oxybate, FT218, if approved by the FDA, has the potential to take a significant share of the twice-nightly sodium oxybate market, which is currently valued at an estimated annualized rate of $1.7 billion.”

Avadel is currently evaluating the timing and process for a commercial launch of Nouress in the United States. In this regard, a competitor received FDA approval earlier this year for its cysteine hydrochloride injection and more recently was granted a U.S. patent, which Avadel is assessing along with other market factors. 

Due to a historical lack of reliable supply, U.S. markets previously imported cysteine hydrochloride injection from Canada under special FDA rules allowing shortage drugs to be sourced abroad if no domestic supplies are available. With FDA approvals of Nouress and another U.S. company’s cysteine hydrochloride injection earlier this year, Avadel expects the domestic supply of cysteine hydrochloride injection will be sufficient to support the entire U.S. market, which, under FDA regulations, should preclude further import or U.S. marketing of unapproved cysteine hydrochloride injection products.  Under these potential market conditions, the U.S. annual market for cysteine hydrochloride could be greater than $50 million. 

https://pubchem.ncbi.nlm.nih.gov/compound/L-Cysteine-hydrochloride

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

https://www.drugbank.ca/salts/DBSALT001754

FDA Approves Conjupri (levamlodipine maleate) for the Treatment of Hypertension

 The board of directors (the “Board”) of CSPC Pharmaceutical Group Limited (the “Company”, together with its subsidiaries, the “Group”) is pleased to announce that Conjupri® (levoamlodipine maleate) tablets has received marketing approval from the U.S. Food and Drug Administration (FDA) for the treatment of hypertension. Based on our knowledge, this is the first New Drug Application (NDA) ever submitted to the FDA by Chinese pharmaceutical companies, and now granted full approval following a standard review by the FDA.

Levoamlodipine is the purified (S)-amlodipine, the pharmacologically active enantiomer in amlodipine (a racemic mixture of (R)- and (S)-amlodipine), for the treatment of hypertension. Amlodipine is a third-generation calcium channel blocker first developed and marketed by Pfizer as NORVASC® (amlodipine besylate) tablets in 2.5 mg, 5.0 mg, and 10.0 mg in 1992. The approved Conjupri® (levoamlodipine maleate) tablets come in 1.25 mg, 2.5 mg and 5.0 mg.

Levoamlodipine maleate tablets have been marketed by the Group as Xuanning ( 玄寧) in China since 2003. The clinical development of levoamlodipine maleate tablets in the U.S. was based on the safety and efficacy data demonstrated in China and data showing that levoamlodipine has less adverse events than amlodipine.

This NDA approval allows the Group to market Conjupri® in the U.S. and also paves the way for marketing in other parts of the world. As the first levoamlodipine approved by the FDA, Conjupri® is qualified to be the reference standard for drugs with the same active ingredient.

The NDA approval of levoamlodipine maleate tablets in the U.S. is a manifestation of the Group’s commitment to innovation and to bringing the best medicines to patients worldwide.

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