Statin Use Associated With Higher Incidence of Diabetes

In continuation of my update on statins

There may be a dose-dependent relationship between statin therapy and new-onset diabetes across the duration of statin use, according to a study recently published in Diabetes Metabolism Research and Reviews.

Victoria A. Zigmont, Ph.D., from The Ohio State University in Columbus, and colleagues used medical records to retrospectively assess the risk of dysglycemia and new-onset diabetes among 7,064 individuals with indications for statin use. At baseline, participants were candidates for statins based on heart disease risk but had not started taking the drugs; 755 patients were eventually prescribed statins during the study period (2011 to 2014).

The researchers found that a higher prevalence of elevated hemoglobin A1c occurred among incident statin users without diabetes. Statin users also had a higher risk of developing new-onset diabetes (adjusted hazard ratio, 2.20). The greatest risk of developing new-onset diabetes was seen among those taking statins for two years or longer (adjusted hazard ratio, 3.33), with no differences seen by statin class or intensity of dose.

"As lifestyle programs like the Diabetes Prevention Program are promoted in primary care settings, we hope physicians will integrate and insurers support healthy lifestyle strategies as part of the optimal management of individuals at risk for both new-onset diabetes and cardiovascular disease," the authors write.

https://medlineplus.gov/statins.html

FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients

The U.S. Food and Drug Administration today approved Mavyret (telaprevir and pibrentasvir) tablets to treat all six genotypes of hepatitis C virus (HCV) in children ages 12 to 17. Mavyret was previously approved to treat HCV in adults in 2017.

   Pibrentasvir

                                  Glecaprevir

“Direct-acting antiviral drugs reduce the amount of HCV in the body by preventing the virus from multiplying, and in most cases, they cure HCV infection,” said Jeffrey Murray, M.D., M.P.H., deputy director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval represents another treatment option for children and adolescents with HCV infection, but for the first time, in all genotypes of HCV.”

HCV is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. According to the U.S. Centers for Disease Control and Prevention, an estimated 2.7 to 3.9 million people in the U.S. have chronic HCV, and children born to HCV-positive mothers are at risk for HCV infection. It is estimated that there are 23,000 to 46,000 children in the U.S. with HCV infection.

With today’s approval, dosing information is provided for Mavyret for the treatment of adult or pediatric patients 12 years and older, or weighing at least 99 pounds, who are infected with any of six identified HCV genotypes either without cirrhosis or with compensated cirrhosis.

The safety and efficacy of Mavyret in pediatric patients was evaluated during clinical trials of 47 patients with genotype 1, 2, 3 or 4 HCV infection without cirrhosis or with mild cirrhosis. Results of the trials demonstrated that 100 percent of patients who received Mavyret for eight or 16 weeks had no virus detected in the blood 12 weeks after finishing treatment, suggesting that patients’ infection had been cured. In pediatric patients with cirrhosis, history of a kidney and/or liver transplant, or genotype 5 or 6 HCV infection, the safety and efficacy of Mavyret are supported by previous studies observed in glecaprevir and pibrentasvir in adults. The adverse reactions observed were consistent with those observed in clinical studies of Mavyret in adults.

Treatment duration with Mavyret differs depending on treatment history, viral genotype and cirrhosis status. The most common adverse reactions in patients taking Mavyret were headache and fatigue. Mavyret is not recommended in patients with moderate cirrhosis and contraindicated in patients with severe cirrhosis. It is also contraindicated in patients taking the drugs atazanavir and rifampin.

Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected adult patients who were undergoing or had completed treatment with HCV direct-acting antivirals, and who were not receiving HBV antiviral therapy. HBV reactivation in patients treated with direct-acting antiviral medicines can result in serious liver problems or death in some patients. Health care professionals should screen all patients for evidence of current or prior HBV infection before starting treatment with Mavyret.

https://www.drugbank.ca/drugs/DB13879

https://pubchem.ncbi.nlm.nih.gov/compound/Glecaprevir#section=Structures

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

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

FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients

FDA Approves Qternmet XR (dapagliflozin, saxagliptin and metformin hydrochloride) for Type 2 Diabetes

In continuation of my update on dapagliflozin, and metformin hydrochloride

 

Dapagliflozin            Saxagliptin                                   and  (Metformin)

The US Food and Drug Administration (FDA) has approved Qternmet XR(dapagliflozin, saxagliptin and metformin hydrochloride) extended release tablets as an oral adjunct treatment to diet and exercise to improve glycaemic control in adults with type-2 diabetes (T2D).

The approval is based on two Phase III trials, which evaluated combinations of dapagliflozin and saxagliptin on a background of metformin over 24 weeks, in patients with inadequately-controlled T2D.

In one trial, treatment with 5mg dapagliflozin/5mg saxagliptin in addition to metformin demonstrated statistically-significant decreases in HbA1c (average blood glucose levels), and an increase in the number of patients achieving the recommended HbA1c treatment goal of <7%. In the second trial, treatment with 10mg dapagliflozin/5mg saxagliptin in addition to metformin extended release demonstrated statistically-significant decreases in HbA1c, and an increase in the number of patients achieving an HbA1c <7%.

The safety results of the individual medicines in these trials were consistent with their known profile.

About Qternmet XR

Qternmet XR is a once-daily, oral medicine compromised of the selective sodium‑glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin, the dipeptidyl peptidase‑4 (DPP‑4) inhibitor saxagliptin and metformin hydrochloride extended release. Qternmet XR is approved in the US as an adjunct to diet and exercise to improve glycaemic control in adults with type-2 diabetes.

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

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

https://www.drugbank.ca/drugs/DB06335

https://www.drugbank.ca/drugs/DB00331

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

FDA Approves Qternmet XR (dapagliflozin, saxagliptin and metformin hydrochloride) for Type 2 Diabetes

FDA Approves Duobrii (halobetasol propionate and tazarotene) Lotion 0.01%/0.045% for Plaque Psoriasis In Adults

In continuation of my update on   tazarotene

 

Ulobetasol                                                                      

                                                                                                                      Tazarotene

Bausch Health Companies Inc. (NYSE/TSX: BHC) and its dermatology business, Ortho Dermatologics, one of the largest prescription dermatology health care businesses, announced,  that the U.S. Food and Drug Administration (FDA) has approved the New Drug Application for Duobrii (halobetasol propionate and tazarotene) Lotion, 0.01%/0.045%, indicated for the topical treatment of plaque psoriasis in adults. Duobrii is the first and only topical lotion that contains a unique combination of halobetasol propionate and tazarotene in one formulation. In a year-long safety study, patients used Duobrii Lotion for up to 24 weeks of continuous use and up to 52 weeks of as-needed use.2 Duobrii is expected to be available in June 2019.

"With today's approval of Duobrii, patients suffering from plaque psoriasis now have an innovative topical treatment option that uniquely combines two well-known ingredients, halobetasol propionate and tazarotene, with established safety profiles, into a single lotion featuring dual mechanisms of action," said Bill Humphries, president, Ortho Dermatologics. "Since psoriasis is a chronic skin disease, patients require continuous treatment in order to achieve optimal control of their symptoms. Now, with Duobrii, health care professionals and their patients have a new topical treatment option that can help them achieve those long-term goals. As a result, we believe that Duobrii has the potential to delay some patients from switching to more expensive biologic treatments, which could potentially result in health care savings."

Continued Mr. Humphries, "We remain committed to bringing forward new medicines, like Duobrii, to add to our portfolio of topicals and biologics to meet the varying treatment needs of patients with psoriasis."

When used separately to treat plaque psoriasis, the duration of use of halobetasol propionate is limited by FDA labeling constraints and the use of tazarotene can be limited due to tolerability concerns. By combining halobetasol propionate and tazarotene in an advanced, patented once-daily moisturizing lotion, the Duobrii formulation ensures uniform distribution, allowing for simultaneous contact with the skin surface.

In the United States, approximately 7.5 million people live with psoriasis, with 80 percent having plaque psoriasis.3 Plaque psoriasis is the most common type of psoriasis, a chronic, non-contagious skin disease that alters the life cycle of skin cells, causing them to build up rapidly on the surface of the skin.

"Duobrii provides the known benefits of a potent topical corticosteroid and a topical retinoid with synergistic efficacy. Combination therapy is the mainstay of topical treatment for plaque psoriasis, making Duobrii an important new option," said Linda Stein Gold, M.D., director, Dermatology Clinical Research, Henry Ford Health System. "Although effective, topical retinoids have had limited use as monotherapy due to tolerability concerns. Duobrii provides improved local tolerability, allowing patients to benefit from an extended duration of use."

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

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

FDA Approves Duobrii (halobetasol propionate and tazarotene) Lotion 0.01%/0.045% for Plaque Psoriasis In Adults

Agios Announces FDA Approval of Tibsovo as Monotherapy for Newly Diagnosed Adult Patients with IDH1 Mutant Acute Myeloid Leukemia (AML) Not Eligible for Intensive Chemotherapy

Agios Pharmaceuticals, Inc., a leader in the field of cellular metabolism to treat cancer and rare genetic diseases,  announced the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to update the U.S. Prescribing Information for Tibsovo, an isocitrate dehydrogenase-1 (IDH1) inhibitor, to include adult patients with newly diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test who are ≥ 75 years old or who have comorbidities that preclude use of intensive induction chemotherapy. The sNDA was granted Priority Review and accepted under the FDA's Real-Time Oncology Review pilot program, which aims to make the review of oncology drugs more efficient by allowing the FDA access to clinical trial data before the information is formally submitted to the agency. Tibsovo received initial FDA approval in July 2018 for adult patients with relapsed or refractory (R/R) AML and an IDH1 mutation1.

“Despite several new AML medicines approved in the last two years, many newly diagnosed patients are still not eligible for existing therapies or combination regimens because of age and other comorbidities,” said Chris Bowden, M.D., chief medical officer at Agios. “With today’s additional Tibsovo approval, we are now able to provide a targeted, oral therapy to patients with an IDH1 mutation who may not have other treatment options. In addition, we are continuing our work to expand the utility of Tibsovo in newly diagnosed AML patients in ongoing Phase 3 trials in combination with both intensive chemotherapy and azacitidine. I would like to thank the patients, nurses, physicians and caregivers who participated in the clinical trial, as well as the tremendous employees at Agios whose focus on patients made this possible.”

AML is a cancer of the blood and bone marrow marked by rapid disease progression and is the most common acute leukemia affecting adults with approximately 20,000 new cases estimated in the U.S. each year2,3. AML patients are typically older or have comorbidities that preclude the use of intensive chemotherapy4. These patients typically have a worse prognosis and poor outcomes5. The majority of patients with AML eventually relapse6. The five-year survival rate is approximately 28%2. For 6 to 10 percent of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia7. IDH1 mutations have been associated with negative prognosis in AML.

“The Phase 1 results for Tibsovo demonstrated that this oral, single agent therapy can induce durable responses in newly diagnosed AML patients with an IDH1 mutation,” said Gail J. Roboz, M.D., Professor of Medicine, Director of the Leukemia Program and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center*. “Many patients included in the study had features associated with particularly aggressive and challenging forms of AML, including secondary disease, adverse risk genetics and prior treatment with hypomethylating agents.”

Tibsovo Safety and Efficacy Data

The efficacy of Tibsovo was evaluated in an open-label, single-arm, multicenter clinical trial (Study AG120-C-001, NCT02074839) that included 28 adult patients with newly diagnosed AML with an IDH1 mutation who were assigned to receive a 500 mg daily dose. The cohort included patients who were age 75 or older or had comorbidities that precluded the use of intensive induction chemotherapy (baseline Eastern Cooperative Oncology Group [ECOG] performance status of ≥2, severe cardiac or pulmonary disease, hepatic impairment with bilirubin >1.5 times the upper limit of normal, or creatinine clearance <45 mL/min). Patients had a median age of 77 years (range of 64 to 87) and 68% had AML with myelodysplasia-related changes. The primary endpoint is the combined complete remission (CR) and complete remission with partial hematologic improvement (CRh) rate. CRh is defined as <5% of blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter).

In this trial, Tibsovo demonstrated:

• CR+CRh rate of 42.9% (12 of 28 patients) (95% CI: 24.5, 62.8).
• The CR rate was 28.6% (8 of 28 patients) (95% CI 13.2, 48.7) and the CRh rate was 14.3% (4 of 28 patients) (95% CI 4.0, 32.7).
• Median durations of CR and CR+CRh were not estimable, with 5 patients (41.7%) who achieved CR or CRh remaining on Tibsovo treatment (treatment duration range: 20.3 to 40.9 months) as of the data cutoff.
• 58.3% (7 of 12) of patients who achieved CR or CRh were in remission at 1 year after receiving treatment.
• For patients who achieved a CR or CRh, the median time to best response of CR or CRh was 2.8 months (range, 1.9 to 12.9 months).
• Among the 17 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 7 (41.2%) became independent of RBC and platelet transfusions during any 56-day post-baseline period.
• Of the 11 patients who were independent of both RBC and platelet transfusions at baseline, 6 (54.5%) remained transfusion independent during any 56-day post-baseline period.

The safety profile of single-agent Tibsovo was evaluated in 28 patients with newly diagnosed AML with an IDH1 mutation treated with a dose of 500 mg daily. The median duration of exposure to Tibsovo was 4.3 months (range, 0.3 to 40.9 months). In the clinical trial, 25% (7 of 28) of patients treated with Tibsovo experienced differentiation syndrome, which can be fatal if not treated. Of the 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. QTc interval prolongation occurred in patients treated with Tibsovo. The most common adverse reactions (≥20%) of any grade in patients with newly diagnosed AML were diarrhea, fatigue, decreased appetite, edema, nausea, leukocytosis, arthralgia, abdominal pain, dyspnea, myalgia, constipation, differentiation syndrome, dizziness, electrocardiogram QT prolonged, mucositis and vomiting.

About Tibsovo (ivosidenib)

Tibsovo is indicated for the treatment of acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in:

Adult patients with newly-diagnosed AML who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.

Adult patients with relapsed or refractory AML.

https://www.rxlist.com/tibsovo-drug.htm#indications

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

Agios Announces FDA Approval of Tibsovo as Monotherapy for Newly Diagnosed Adult Patients with IDH1 Mutant Acute Myeloid Leukemia (AML) Not Eligible for Intensive Chemotherapy

FDA Approves Ruzurgi (amifampridine) for Children with Lambert-Eaton Myasthenic Syndrome

In continuation of my update on amifampridine

The U.S. Food and Drug Administration approved Ruzurgi (amifampridine) tablets for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in patients 6 years to less than 17 years of age. This is the first FDA approval of a treatment specifically for pediatric patients with LEMS. The only other treatment approved for LEMS is only approved for use in adults.

“We continue to be committed to facilitating the development and approval of treatments for rare diseases, particularly those in children,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities.”

LEMS is a rare autoimmune disorder that affects the connection between nerves and muscles and causes weakness and other symptoms in affected patients. In people with LEMS, the body’s own immune system attacks the neuromuscular junction (the connection between nerves and muscles) and disrupts the ability of nerve cells to send signals to muscle cells. LEMS may be associated with other autoimmune diseases, but more commonly occurs in patients with cancer such as small cell lung cancer, where its onset precedes or coincides with the diagnosis of cancer. LEMS can occur at any age. The prevalence of LEMS specifically in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide.

Use of Ruzurgi in patients 6 to less than 17 years of age is supported by evidence from adequate and well-controlled studies of the drug in adults with LEMS, pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients and safety data from pediatric patients 6 to less than 17 years of age.

The effectiveness of Ruzurgi for the treatment of LEMS was established by a randomized, double-blind, placebo-controlled withdrawal study of 32 adult patients in which patients were taking Ruzurgi for at least three months prior to entering the study. The study compared patients continuing on Ruzurgi to patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients that continued on Ruzurgi experienced less impairment than those on placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness that evaluated the feeling of weakening or strengthening. The scores indicated greater perceived weakening in the patients switched to placebo.

The most common side effects experienced by pediatric and adult patients taking Ruzurgi were burning or prickling sensation (paresthesia), abdominal pain, indigestion, dizziness and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Patients should inform their health care professional immediately if they have signs of hypersensitivity reactions such as rash, hives, itching, fever, swelling or trouble breathing.

The FDA granted this application Priority Review and Fast Track designations. Ruzurgi also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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

FDA Approves Ruzurgi (amifampridine) for Children with Lambert-Eaton Myasthenic Syndrome

FDA Approves Bavencio (avelumab) Plus Inlyta (axitinib) Combination for Patients with Advanced Renal Cell Carcinoma

In continuation of my update on axitinib

Merck KGaA, Darmstadt, Germany, which operates its biopharmaceutical business as EMD Serono in the US and Canada, and Pfizer Inc. (NYSE: PFE) today announced that the US Food and Drug Administration (FDA) has approved Bavencio (avelumab) in combination with Inlyta (axitinib) for the first-line treatment of patients with advanced renal cell carcinoma (RCC). This is the first FDA approval for an anti-PD-L1 therapy as part of a combination regimen for patients with advanced RCC. The approval of Bavencio in combination with Inlyta was based on positive results from the Phase III JAVELIN Renal 101 study (NCT02684006), in which the combination significantly improved median progression-free survival (PFS) compared with sunitinib by more than five months in the intent-to-treat (ITT) patient population (HR: 0.69 [95% CI: 0.56–0.84]; 2-sided p-value=0.0002; median PFS for Bavencio in combination with Inlyta: 13.8 months [95% CI: 11.1-NE]; sunitinib: 8.4 months [95% CI: 6.9-11.1]). The ITT population included patients regardless of PD-L1 expression and across IMDC (International Metastatic Renal Cell Carcinoma Database) prognostic risk groups (favorable 21%, intermediate 62% and poor 16%).

“As we look to continue to improve outcomes for people with advanced RCC, new treatment approaches have the potential to benefit patients,” said Robert J. Motzer, M.D., Jack and Dorothy Byrne Chair in Clinical Oncology, Memorial Sloan Kettering Cancer Center, New York, US, and principal investigator for JAVELIN Renal 101. “With today’s FDA approval of avelumab in combination with axitinib, we can now offer patients with advanced RCC a first-line treatment option that combines a PD-L1 immunotherapy with a well-known VEGFR TKI to provide a significant reduction in the risk of disease progression or death and doubling of the response rate compared with sunitinib.”

RCC is a type of cancer where PD-L1 expression may contribute to inhibition of the immune response against the tumor.2 It is also a highly vascular tumor, in which vascular endothelial growth factor (VEGF) plays a key role.3

“A kidney cancer diagnosis is life-changing for both patients and their loved ones, and having a treatment strategy for their disease quickly becomes a priority,” said Dena Battle, President, KCCure. “The approval of new treatments such as Bavencio in combination with Inlyta gives patients with advanced RCC much-needed options.”

There is a significant unmet need for first-line treatments that delay progression and have an acceptable safety profile. Approximately 20% to 30% of patients are first diagnosed with RCC at the advanced stage, and 30% of patients treated for an earlier stage go on to develop metastases.4,5 About half of patients living with advanced RCC do not go on to receive additional treatment after first-line therapy,6,7 for reasons that may include poor performance status or adverse events from their initial treatment.6,8,9

“Today’s approval of Bavencio in combination with Inlyta builds on Pfizer’s long heritage in bringing innovation to the RCC community with the hopes of making a significant and meaningful impact on the lives of patients,” said Andy Schmeltz, Global President, Pfizer Oncology. “For more than 12 years, Pfizer has led the field in its commitment to developing new treatments for patients with advanced kidney cancer.”

“With today’s FDA approval of Bavencio in combination with Inlyta, we feel privileged that we can offer patients with first-line advanced renal cell carcinoma a new treatment option,” said Rehan Verjee, President, EMD Serono, and Global Head of Innovative Medicine Franchises, Merck KGaA, Darmstadt, Germany.

In JAVELIN Renal 101, the objective response rate (ORR) was doubled in the ITT population with Bavencio in combination with Inlyta versus sunitinib (51.4% [95% CI: 46.6-56.1] vs. 25.7% [95% CI: 21.7-30.0]). With a median overall survival (OS) follow-up of 19 months, data for the trial’s other primary endpoint of OS were immature, with 27% of deaths in the ITT population, and the trial is continuing as planned. The most common adverse reactions (≥20%) were diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Serious adverse reactions occurred in 35% of patients receiving Bavencio in combination with Inlyta. The incidence of major adverse cardiovascular events (MACE) was higher with Bavencio in combination with Inlyta versus sunitinib.1 Findings from the study have been published in The New England Journal of Medicine.10

The European Medicines Agency (EMA) validated the Type II variation application for Bavencio in combination with Inlyta in advanced RCC in March 2019, and a supplemental application for Bavencio in combination with Inlyta in unresectable or metastatic RCC was submitted in Japan in January 2019.

The alliance is committed to providing patient access and reimbursement support through its CoverOne® program to patients who have been prescribed Bavencio. This program provides a spectrum of patient access and reimbursement support services intended to help US patients prescribed Bavencio receive appropriate access. CoverOne may be reached by phone at 844-8COVER1 (844-826-8371) or online at www.CoverOne.com.

Pfizer is committed to ensuring that patients who are prescribed Inlyta have access to this innovative therapy. Patients in the US have access to Pfizer Oncology Together™, which offers personalized support and financial assistance resources to help patients access their prescribed Pfizer Oncology medications. For more information, please call 1-877-744-5675 or visit PfizerOncologyTogether.com.

In an effort to streamline the patient enrollment process, EMD Serono and Pfizer have partnered to create a single enrollment form for the Bavencio and Inlyta combination for patients with advanced RCC that can be processed through both CoverOne and Pfizer Oncology Together. Each program will independently conduct the access and reimbursement activities for the product for which it is responsible.

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





FDA Approves Bavencio (avelumab) Plus Inlyta (axitinib) Combination for Patients with Advanced Renal Cell Carcinoma

Common Diabetes Drug Invokana (canagliflozin) May Also Shield Kidneys, Heart

In continuation of my update on canagliflozin

A common diabetes drug may also greatly reduce the odds for death from kidney failure and heart disease in diabetes patients with kidney disease, a new study finds.

  

The news on Invokana (canagliflozin) is important, experts say, because diabetes and kidney trouble so often go together.

"Diabetes is the leading cause of kidney failure worldwide, but for almost two decades there have been no new treatments to protect kidney function," noted study lead author Vlado Perkovic. He's a professor at The George Institute for Global Health at Oxford University in the United Kingdom.

"This definitive trial result is a major medical breakthrough as people with diabetes and kidney disease are at extremely high risk of kidney failure, heart attack, stroke and death," Perkovic said in a university news release. "We now have a very effective way to reduce this risk using a once-daily pill."

The research was paid for by drug company Janssen, which makes Invokana. The study involved more than 4,400 patients with diabetes and kidney disease across 34 countries. Half took Invokana and half took a "dummy" placebo pill. All of them received care for kidney disease according to current guidelines.

Those who took Invokana had a 30% lower risk of developing kidney failure, a 30% lower risk of dying from kidney failure or heart disease, a 20% lower risk of major heart events such as heart attack, stroke, or heart-related death, and a 39% lower risk of hospitalization for heart failure, the researchers reported.

The findings were published April 15 in the New England Journal of Medicine.

There was no higher risk of major side effects among those who took Invokana, according to the study, which was also due to be presented Monday at the ISN World Congress of Nephrology, in Melbourne, Australia.

Invokana is from a class of diabetes medicines known as sodium glucose transporter 2 (SGLT2) inhibitors.

Study co-author Meg Jardine, associate professor at The George Institute, said, "With 5 million people worldwide predicted to have kidney failure by 2035, this is a major breakthrough."

Two experts in diabetes and renal (kidney) care who read over the new study agreed the findings are significant.

"Upwards of 40% of end-stage renal disease patients have diabetes as the cause of their renal failure," noted Dr. Maria DeVita, chief of nephrology at Lenox Hill Hospital in New York City.

She explained that SGLT2 inhibitor medicines like Invokana work by blocking the "reuptake" of glucose within the kidney. More of this blood sugar, as well as salt, are therefore excreted harmlessly in urine instead of lingering in the kidneys where they can do damage, DeVita said.

So, Invokana "may substantially change the trajectory of kidney decline, preserving kidney function for years longer than we thought possible for the long term," DeVita said. "This is wonderful news for those with diabetic kidney disease."

Dr. Guy Mintz directs cardiovascular health at the Sandra Atlas Bass Heart Hospital in Manhasset, N.Y. He also believes the new findings are "exciting."

"With another impressive study of this family of medications, SGLT2 inhibitors should now be utilized in all type 2 diabetic patients with kidney disease and increased cardiovascular risk," as long as there are no reasons not to do so, Mintz believes.

"This is another tool in our belt to reduce progressive kidney disease and cardiac events in our type 2 diabetic population with kidney disease," he said.    

https://www.drugbank.ca/drugs/DB08907

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

 



Common Diabetes Drug Invokana (canagliflozin) May Also Shield Kidneys, Heart 

Balversa (erdafitinib) Approved for Advanced Bladder Cancer

Balversa (erdafitinib) has been approved by the U.S. Food and Drug Administration to treat adults with advanced or spreading bladder cancer caused by a genetic defect called FGFR3 or FGFR2, the agency said in a news release.

"We're in an era of more personalized or precision medicine, and the ability to target cancer treatment to a patient's specific genetic mutation or biomarker is becoming the standard, with advances being made in new disease types. Today's approval represents the first personalized treatment targeting susceptible FGFR genetic alternations for patients with metastatic bladder cancer," said Dr. Richard Pazdur, director of the FDA's Oncology Center of Excellence.

Bladder cancer is the sixth most common cancer in the United States, the FDA said. About 20 percent of people with the disease have an FGFR mutation.

Balversa was clinically studied in a trial involving 87 people with advanced or metastatic bladder cancer and the FGFR3 or FGFR2 genetic mutation who hadn't responded to chemotherapy, the FDA said. About one-third of those given the drug had a complete or partial response to the medication; the average response lasting about 5 1/2 months.

Common side effects of Balversa included a jump in phosphate levels, mouth sores, feeling tired, changes in kidney function, diarrhea, dry mouth and changes in liver function.

Balversa may trigger serious eye problems, including inflamed eyes, inflamed cornea and disorders of the retina, the agency warned.

Doctors and other health professionals should tell men with female partners of child-bearing potential to use contraception during treatment with Balversa and for one month after the last dose, the FDA said. Women who are pregnant or breastfeeding shouldn't take Balversa because it may harm a developing fetus or newborn.

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

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

Balversa (erdafitinib) Approved for Advanced Bladder Cancer 

Mayzent Approved for Relapsing MS

Mayzent (siponimod) pills have been approved by the U.S. Food and Drug Administration for adults with relapsing multiple sclerosis (MS).

"Multiple sclerosis can have a profound impact on a person's life," said Dr. Billy Dunn, director of the agency's Division of Neurology Products.

MS is an autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. Most people have initial symptoms between the ages of 20 and 40, and MS strikes more women than men, the FDA said in a news release.

Many people with MS are left permanently disabled and worsen over time, the agency said.

Mayzent's effectiveness was shown in clinical studies of 1,651 people. Progression of disability was significantly lower among those who took Mayzent than in a group that took a placebo. Mayzent also decreased the number of relapses, the FDA said.

The drug must be accompanied by a patient medication guide that describes the medication's uses and risks. Since Mayzent may raise the risk of infections, users should have a complete blood count before treatment starts. And users should contact their doctor if they have any vision changes, changes in heart rate or trouble breathing, the FDA said.

Since Mayzent may harm a developing fetus, women of childbearing age should use contraception during treatment and for 10 days after stopping the drug.

Mayzent's most common side effects include headache, high blood pressure and liver problems.

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

Mayzent Approved for Relapsing MS 

FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose

In continuation of my update on naloxone 

   

The first generic naloxone nasal spray to treat opioid overdose has received approval from the U.S. Food and Drug Administration.

Teva Pharmaceuticals' lifesaving product is also the first generic naloxone nasal spray approved for use by people without medical training. There was already a brand-name spray (Narcan) for emergency use by untrained people, such as family members and bystanders.

The need is urgent. On average, more than 130 Americans die every day from overdoses of opioids -- including prescription painkillers such as fentanyl, oxycodone (OxyContin), hydrocodone (Vicodin) and morphine, as well as illegal drugs such as heroin or drugs sold as heroin, the FDA said.

"In the wake of the opioid crisis, a number of efforts are underway to make this emergency overdose reversal treatment more readily available and more accessible," said Dr. Douglas Throckmorton, deputy center director for regulatory programs in the FDA's Center for Drug Evaluation and Research.

"In addition to this approval of the first generic naloxone nasal spray, moving forward we will prioritize our review of generic drug applications for naloxone," he added.

When someone overdoses on opioids, breathing may become shallow or stop completely, leading to death if no one intervenes. If administered quickly, naloxone can counter the effects within minutes.

Throckmorton said in an agency news release that the FDA is also helping drugmakers pursue approval of an over-the-counter naloxone product, and "exploring other ways to increase availability of naloxone products intended for use in the community."

The FDA is also considering whether naloxone should be routinely prescribed along with all or some opioid prescriptions in order to reduce the risk of overdose.

"Altogether, these efforts have the potential to put a vital tool for combating opioid overdose in the hands of those who need it most -- friends and families of opioid users, as well as first responders and community-based organizations," Throckmorton said.

Nearly 400,000 people in the United States died of opioid overdoses between 1999 and 2017, according to the U.S. Centers for Disease Control and Prevention.

"We're committed to working with other federal, state and local officials, as well as health care providers, patients and communities across the country to combat the staggering human and economic toll created by opioid abuse and addiction," Throckmorton said in the news release.

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

FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose