FDA Approves Apretude

 

ViiV Healthcare, the global specialist HIV company majority owned by GlaxoSmithKline plc (GSK), with Pfizer Inc. (Pfizer) and Shionogi Limited (Shionogi) as shareholders,  announced the US Food and Drug Administration (FDA) approval of Apretude, the first and only long-acting injectable pre-exposure prophylaxis (PrEP) option to reduce the risk of sexually acquired HIV-1. The long-acting injectable was approved for use in adults and adolescents weighing at least 35 kg who are at risk of sexually acquiring HIV and who have a negative HIV-1 test prior to initiation. The medicine was studied in men who have sex with men, as well as women and transgender women who have sex with men, who were at increased risk of sexually acquiring HIV.

Cabotegravir long-acting for PrEP is provided as an injection given as few as six times per year and is initiated with a single 600 mg (3-ml) injection given one month apart for two consecutive months. After the second initiation injection, the recommended continuation injection dose is a single 600 mg (3-ml) injection given every two months. Vocabria (cabotegravir oral tablets) may be administered for approximately one month before initiating the first injection to assess the tolerability of the medicine.

Deborah Waterhouse, CEO, ViiV Healthcare, said: “People who are vulnerable to acquiring HIV, especially those in Black and Latinx communities who are disproportionately impacted in the US, may want options beyond daily oral pills. That’s why ViiV Healthcare is proud that Apretude was studied in one of the most diverse and comprehensive HIV prevention trial programs to date, which also included some of the largest numbers of transgender women and Black men who have sex with men ever enrolled in an HIV prevention trial. With Apretude, people can reduce the risk of acquiring HIV with as few as six injections a year. Today’s approval is the latest example of ViiV Healthcare’s commitment to developing long-acting medicines that offer consumers a different choice.”

US FDA approval is based on the results from two international phase IIb/III multicenter, randomised, double-blind, active-controlled trials, HPTN 083 and HPTN 084, which evaluated the safety and efficacy of cabotegravir long-acting for PrEP in HIV-negative men who have sex with men, transgender women, and cisgender women, who were at increased risk of sexually acquiring HIV. In these trials, which included more than 7,700 participants across 13 countries combined, the blinded, randomised portions of both trials were stopped early by an independent Data Safety Monitoring Board after cabotegravir long-acting for PrEP was shown to be superior to daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) tablets in preventing the acquisition of HIV in study participants. Clinical trial participants who received cabotegravir long-acting for PrEP experienced a 69% lower incidence of HIV compared to FTC/TDF tablets in HPTN 083 and a 90% lower incidence of HIV compared to FTC/TDF tablets in HPTN 084.

The most common adverse reactions (all grades) observed in at least 1% of clinical trial participants receiving cabotegravir long-acting for PrEP were injection site reactions, diarrhoea, headache, pyrexia, fatigue, sleep disorders, nausea, dizziness, flatulence, abdominal pain, vomiting, myalgia, rash, decreased appetite, somnolence, back pain, and upper respiratory tract infection. Adverse events led to discontinuation in 6% of participants in HPTN 083 and 1% of participants in HPTN 084.

In HPTN 083, participants in the US were inclusive of the Black/African American and Latinx communities of men and transgender women who have sex with men, who are disproportionately affected by the HIV epidemic and comprise the greatest percentage of new HIV diagnoses. In HPTN 084, all participants were cisgender women from sub-Saharan Africa. Women in this region bear a disproportionate burden of the HIV epidemic and may be twice as likely to acquire HIV as their male counterparts.

Richard Elion, MD, Director of Research at Washington Health Institute, said: “We have the tools to end the HIV epidemic through the implementation of effective antiretroviral treatment and HIV prevention. PrEP has played a vital role in protecting people from acquiring HIV. With the availability of cabotegravir long-acting for PrEP as an injection every two months to prevent HIV, people now have an important new option besides daily medication. This long-acting medication offers more options for prevention, and now providers and patients will be empowered by choices and the ability to choose the approach that is optimal for each individual.”

HIV continues to be a global public health crisis, with an estimated 38 million people living with HIV worldwide and 1.7 million new cases annually. PrEP represents an effective tool to reduce new cases of HIV, which in addition to successful HIV antiretroviral treatment, will help efforts to end the HIV epidemic. However, fewer than 25% of the people who could benefit from PrEP in the US are currently taking it. Despite the wide availability of daily oral PrEP, it can be limited by inconsistent adherence as well as structural and cultural barriers that lead to underutilisation in key populations.

https://www.drugs.com/apretude.html

https://www.drugs.com/newdrugs/fda-approves-apretude-cabotegravir-extended-release-injectable-suspension-hiv-pre-exposure-5754.html

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FDA Approves Zeposia (ozanimod) for Relapsing Forms of Multiple Sclerosis

Myers Squibb Company (NYSE: BMY)  announced that the U.S. Food and Drug Administration (FDA) approved Zeposia (ozanimod) 0.92 mg for the treatment of adults with relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.1 Zeposia, an oral medication taken once daily, is the only approved sphingosine-1-phosphate (S1P) receptor modulator that offers RMS patients an initiation with no genetic test and no label-based first-dose observation required for patients.1,4,5 An up-titration scheme should be used to reach the maintenance dosage of Zeposia, as a transient decrease in heart rate and atrioventricular conduction delays may occur.

Multiple sclerosis (MS) is a disease in which the immune system attacks the protective myelin sheath that covers the nerves, creating damaging lesions that make it harder for signals to travel between each nerve cell.6,7 This “signal breakdown” can lead to symptoms and relapses.6,8

“With the FDA approval of Zeposia, appropriate patients with relapsing forms of multiple sclerosis will have another oral treatment option with meaningful efficacy to help address the disease’s hallmark relapses and brain lesions,”9 said Samit Hirawat, M.D., chief medical officer, Bristol Myers Squibb. “Zeposia has substantial clinical potential, and we are well positioned with our heritage in transformational science to ensure this innovative compound ultimately benefits as many patients as possible.”

The approval is based on data from the largest pivotal, head-to-head RMS studies with an active comparator to date: the randomized, active-controlled Phase 3 SUNBEAM™ (safety and efficacy of Zeposia versus interferon beta-1a in relapsing multiple sclerosis) and RADIANCE™ (safety and efficacy of the selective sphingosine 1-phosphate receptor modulator Zeposia in relapsing multiple sclerosis) Part B clinical trials of more than 2,600 adults.1,2,3,10 In both trials – as compared to AVONEX® (interferon beta-1a), Zeposia delivered powerful efficacy as measured by annualized relapse rate (ARR), as well as on the number and size of brain lesions.1,2,3

• Zeposia demonstrated a relative reduction in ARR versus AVONEX of 48% through one year and 38% at two years (absolute ARR of 0.18 versus 0.35 and 0.17 versus 0.28, respectively).1,2,3
• At one year, treatment with Zeposia reduced the number of T1-weighted gadolinium-enhanced (GdE) brain lesions more than AVONEX (0.16 vs 0.43), a relative reduction of 63%, and reduced the number of new or enlarging T2 lesions (1.47 vs. 2.84), a relative reduction of 48%.1,3
• At two years, treatment with Zeposia reduced the number of T1-weighted gadolinium-enhanced (GdE) brain lesions more than AVONEX (0.18 vs 0.37), a relative reduction of 53%.1,2 Zeposia also reduced the number of new or enlarging T2 lesions vs AVONEX (1.84 vs 3.18), a relative reduction of 42%.1,2

There was no statistically significant difference in the three-month and six-month confirmed disability progression between Zeposia- and AVONEX- treated patients over two years.1

Zeposia demonstrated acceptable safety and tolerability in the Phase 3 SUNBEAM and RADIANCE Part B trials.1,2,3 Zeposia is contraindicated in patients who in the last six months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure; patients who have a presence of Mobitz type II second or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial, unless the patient has a functioning pacemaker; patients with severe untreated sleep apnea; and patients taking a monoamine oxidase inhibitor.1 Zeposia is associated with the following Warnings and Precautions: increased risk of infections, bradyarrhythmia and atrioventricular conduction delays, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, posterior reversible encephalopathy syndrome, additive immunosuppressive effects from prior immune-modulating treatments, severe increase in disability after stopping Zeposia, and immune system effects after stopping Zeposia.1 Please see Important Safety Information for additional details. The most common adverse reactions (incidence ≥4%) were upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.1

Before initiation of treatment with Zeposia, all patients require assessments including a recent complete blood count including lymphocyte count (within six months or after discontinuation of prior MS therapy), an ECG to determine whether preexisting conduction abnormalities are present, a recent liver function test (within six months), and consideration of current and prior medications, including vaccinations.¹ For patients with a history of uveitis or macular edema, an ophthalmic assessment is required.

Treatment for relapsing forms of multiple sclerosis is critical to address this devastating neurological disease.11 I’m excited, with the introduction of Zeposia, I will have a new oral option to offer my RMS patients that has demonstrated efficacy and safety,”1 said Bruce Cree, M.D., Ph.D., M.A.S., professor of clinical neurology, University of California San Francisco (UCSF) Weill Institute for Neurosciences and clinical research director, UCSF MS Center.

“Multiple sclerosis is an unpredictable and often disabling disease that affects nearly one million people in the United States.9,12 Ongoing treatment with disease-modifying therapy can reduce the number of disease attacks,”11 said Bruce Bebo, executive vice president of research, National Multiple Sclerosis Society. “Each person can respond differently to these medications, which is why having treatment options is so important. We are pleased that there will now be another effective treatment option for people with MS.”

As the country’s healthcare system is dealing with the unprecedented COVID-19 pandemic, Bristol Myers Squibb has made the decision to delay commercialization of Zeposia. The Company made the decision based on what’s in the best health interest of our patients, customers and employees. Bristol Myers Squibb will continue to monitor the environment and will partner with the neurology community to inform launch timing.

A Marketing Authorization Application for Zeposia for the treatment of adults with relapsing-remitting multiple sclerosis in the European Union is currently under review with the European Medicines Agency (EMA). A regulatory decision from the EMA is expected in the first half of 2020.

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

FDA Approves Zeposia (ozanimod) for Relapsing Forms of Multiple Sclerosis

FDA Approves Isturisa (osilodrostat) for the Treatment of Cushing’s Disease

The U.S. Food and Drug Administration today approved Isturisa (osilodrostat) oral tablets for adults with Cushing’s disease who either cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease. 

Cushing’s disease is a rare disease in which the adrenal glands make too much of the cortisol hormone. Isturisa is the first FDA-approved drug to directly address this cortisol overproduction by blocking the enzyme known as 11-beta-hydroxylase and preventing cortisol synthesis.

“The FDA supports the development of safe and effective treatments for rare diseases, and this new therapy can help people with Cushing’s disease, a rare condition where excessive cortisol production puts them at risk for other medical issues,” said Mary Thanh Hai, M.D., acting director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research. “By helping patients achieve normal cortisol levels, this medication is an important treatment option for adults with Cushing’s disease.”

Cushing’s disease is caused by a pituitary tumor that releases too much of a hormone called adrenocorticotropin, which stimulates the adrenal gland to produce an excessive amount of cortisol. The disease is most common among adults between the ages of 30 to 50, and it affects women three times more often than men. Cushing’s disease can cause significant health issues, such as high blood pressure, obesity, type 2 diabetes, blood clots in the legs and lungs, bone loss and fractures, a weakened immune system and depression. Patients may have thin arms and legs, a round red full face, increased fat around the neck, easy bruising, striae (purple stretch marks) and weak muscles.

Isturisa’s safety and effectiveness for treating Cushing’s disease among adults was evaluated in a study of 137 adult patients (about three-quarters women) with a mean age of 41 years. The majority of patients either had undergone pituitary surgery that did not cure Cushing’s disease or were not surgical candidates. In the 24-week, single-arm, open-label period, all patients received a starting dose of 2 milligrams (mg) of Isturisa twice a day that could be increased every two weeks up to 30 mg twice a day. At the end of this 24-week period, about half of patients had cortisol levels within normal limits. After this point, 71 patients who did not need further dose increases and tolerated the drug for the last 12 weeks entered an eight-week, double-blind, randomized withdrawal study where they either received Isturisa or a placebo (inactive treatment). At the end of this withdrawal period, 86% of patients receiving Isturisa maintained cortisol levels within normal limits compared to 30% of patients taking the placebo.

The most common side effects reported in the clinical trial for Isturisa were adrenal insufficiency, headache, vomiting, nausea, fatigue and edema (swelling caused by fluid retention). Hypocortisolism (low cortisol levels), QTc prolongation (a heart rhythm condition) and elevations in adrenal hormone precursors (inactive substance converted into a hormone) and androgens (hormone that regulates male characteristics) may also occur in people taking Isturisa.

Isturisa is taken by mouth twice a day, in the morning and evening as directed by a health care provider. After treatment has started, a provider may re-evaluate dosage, depending upon the patient’s response.

Isturisa received Orphan Drug Designation, which is a special status granted to a drug intended to treat a rare disease or condition.

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

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FDA Approves Isturisa (osilodrostat) for the Treatment of Cushing’s Disease

Ipsen Announces U.S. FDA Approval for Newly Designed Pre-Filled Syringe for Somatuline Depot (lanreotide)

 

Ipsen Biopharmaceuticals, an affiliate of Ipsen , announced today that the United States Food and Drug Administration (FDA) has approved a new pre-filled syringe for Somatuline Depot (lanreotide). The syringe includes updated features, such as larger flanges, designed to help make it easier for healthcare providers to administer the injection.1 The indications remain the same as those for the previous pre-filled syringe and include the treatment of adult patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival; treatment of adults with carcinoid syndrome; when used, it reduces the frequency of short-acting somatostatin analog rescue therapy; and the long-term treatment of patients with acromegaly who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option. Please see Important Safety Information below and accompanying full Prescribing Information.

“The conditions of GEP-NETs and acromegaly can be associated with a number of uncomfortable and unpleasant symptoms, and innovation aimed at improving the injection process is a step forward,” said Daphne Adelman, Clinical Nurse Specialist, Northwestern University, Chicago, and one of the authors of the study.

Ipsen conducted five separate but complementary studies in partnership with patients, their caregivers, nurses and other healthcare professionals to better understand the current use of the existing Somatuline® Depot pre-filled syringe and to evaluate ways to improve the features of the device.1 The result of this collaboration is a redesigned delivery system intended to make it easy to grip the syringe and administer the injection. The new syringe features a needle shield removal system, more stable plunger and thermoform tray that has recessed areas designed to help prevent accidental plunger depression. The built-in safety system, which may help to prevent needle stick injury by locking in place following the administration, has not been changed.

“We consistently look for opportunities to respond to the needs of the communities we serve, and this approval would not have been possible without the direct involvement of nurses and the patients with GEP-NETs and acromegaly whom they treat,” said Bradley Bailey, SVP, and Franchise Head Oncology/Endocrinology Business Unit at Ipsen. “We listened and collaborated to enhance the existing pre-filled syringe, making it sturdier for healthcare providers when administering treatment, with the intention of improving the injection process. We look forward to bringing this innovation to healthcare providers for their patients soon.”

The new pre-filled syringe is for deep subcutaneous injection and is intended for administration by a healthcare professional. Healthcare providers can expect to receive the new syringe during Q3 2019. The device is approved for use in the U.S., EU and additional ex-U.S. markets.

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 Jatenzo (testosterone undecanoate) for Certain Forms of Hypogonadism

 The U.S. Food and Drug Administration  approved Jatenzo (testosterone undecanoate), an oral testosterone capsule to treat men with certain forms of hypogonadism. These men have low testosterone levels due to specific medical conditions, such as genetic disorders like Klinefelter syndrome or tumors that have damaged the pituitary gland. Jatenzo should not be used to treat men with “age-related hypogonadism,” in which testosterone levels decline due to aging, even if these men have symptoms that appear to be related to low testosterone. Jatenzo’s benefits do not outweigh its risks for that use.

“Jatenzo’s oral route of administration provides an important addition to current treatment options available for men with certain hypogonadal conditions who up until now have most commonly been treated with testosterone products that are applied to the skin or injected,” said Hylton V. Joffe, M.D, M.M.Sc., director of the Division of Bone, Reproductive and Urologic Products in the FDA’s Center for Drug Evaluation and Research. “But it’s important to emphasize that this drug should not, like other testosterone treatments, be used to treat older men with ‘age-related hypogonadism.’ The benefits of testosterone therapy, including Jatenzo, have not been established for this use, and Jatenzo’s effects on raising blood pressure can increase the risks of heart attack, stroke and cardiovascular death in this population.”

The efficacy of Jatenzo was demonstrated in a four-month clinical trial involving 166 men with hypogonadism. Study participants initially were given Jatenzo at a dose of 237 mg twice per day, and the dose was adjusted downward or upward to a maximum of 396 mg twice per day on the basis of testosterone levels. Eighty-seven percent of Jatenzo-treated men achieved an average testosterone level within the normal range, which was the primary study endpoint.

Jatenzo contains a boxed warning on its labeling stating that the drug can cause blood pressure to rise, increasing the risk of heart attack, stroke and cardiovascular death. Health care providers should consider a patient’s individual heart disease risks and ensure that blood pressure is adequately controlled before prescribing Jatenzo; they should also periodically monitor patient blood pressure during treatment. Jatenzo is currently one of two testosterone products that have this boxed warning. The FDA is requiring all testosterone product manufacturers to conduct blood pressure postmarketing trials to more clearly address whether these products increase blood pressure.

Common side effects, occurring in more than 2 percent of patients in the Jatenzo clinical trial, included headache, an increase in hematocrit (red blood cell count), a decrease in high-density lipoprotein cholesterol (“good” cholesterol), high blood pressure and nausea. An increase in prostate specific antigen (PSA) was also observed. Patients should have their hematocrit, cholesterol and PSA monitored regularly to check for changes. Those with benign prostate hyperplasia should be monitored for worsening of symptoms.

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

FDA Approves Jatenzo (testosterone undecanoate) for Certain Forms of Hypogonadism

FDA Approves Spravato (esketamine) Nasal Spray for Treatment-Resistant Depression

  In continuation of my update on esketamine

The U.S. Food and Drug Administration   approved Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant, for the treatment of depression in adults who have tried other antidepressant medicines but have not benefited from them (treatment-resistant depression). Because of the risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration, and the potential for abuse and misuse of the drug, it is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS).

"There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition," said Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research. "Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA’s drug approval process including a robust discussion with our external advisory committees, were important to our decision to approve this treatment. Because of safey concerns, the drug will only be available through a restricted distribution system and it must be administered in a certified medical office where the health care provider can monitor the patient."

Patients with major depressive disorder who, despite trying at least two antidepressant treatments given at adequate doses for an adequate duration in the current episode, have not responded to treatment are considered to have treatment-resistant depression.

The Spravato labeling contains a Boxed Warning that cautions that patients are at risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug. Because of the risk of sedation and dissociation, patients must be monitored by a health care provider for at least two hours after receiving their Spravato dose. The REMS requires the prescriber and the patient to both sign a Patient Enrollment Form that clearly states that the patient understands they should make arrangements to safely leave the health care setting to get home and that the patient should not drive or use heavy machinery for the rest of the day on which they receved the drug. Additionally, Spravato must be dispensed with a patient Medication Guide that outlines the drug’s uses and risks.

The patient self-administers Spravato nasal spray under the supervision of a health care provider in a certified doctor’s office or clinic, and the spray cannot be taken home. The health care provider will instruct the patient on how to operate the nasal spray device. During and after each use of the nasal spray device, the health care provider will check the patient and determine when the patient is ready to leave.

The efficacy of Spravato was evaluated in three short-term (four-week) clinical trials and one longer-term maintenance-of-effect trial. In the three short-term studies, patients were randomized to receive Spravato or a placebo nasal spray. In light of the serious nature of treatment-resistant depresison and the need for patients to receive some form of treatment, all patients in these studies started a new oral antidepressant at the time of randomization and the new antidepressant was continued throughout the trials. The primary efficacy measure was the change from baseline on a scale used to assess the severity of depressive symptoms. In one of the short-term studies, Spravato nasal spray demonstrated statistically significant effect compared to placebo on the severity of depression, and some effect was seen within two days. The two other short-term trials did not meet the pre-specified statistical tests for demonstrating effectiveness. In the longer-term maintenance-of-effect trial, patients in stable remission or with stable response who continued treatment with Spravato plus an oral antidepressant experienced a statistically significantly longer time to relapse of depressive symptoms than patients on placebo nasal spray plus an oral antidepressant.

The most common side effects experienced by patients treated with Spravato in the clinical trials were disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk.

Patients with unstable or poorly controlled hypertension or pre-existing aneurysmal vascular disorders may be at increased risk for adverse cardiovascular or cerebrovascular effects. Spravato may impair attention, judgment, thinking, reaction speed and motor skills. Patients should not drive or operate machinery until the next day after a restful sleep. Spravato may cause fetal harm and women of reproductive potential should consider pregnancy planning and prevention; women should not breastfeed while being treated.

Esketamine is the s-enantiomer of ketamine. Ketamine is a mixture of two enantiomers (mirror image molecules). This is the first FDA approval of esketamine for any use. The FDA approved ketamine (Ketalar) in 1970.

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

FDA Approves Spravato (esketamine) Nasal Spray for Treatment-Resistant Depression

FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression

  

 The Janssen Pharmaceutical Companies of Johnson & Johnson  announced that the U.S. Food and Drug Administration (FDA) Psychopharmacologic Drug Advisory Committee and Drug Safety and Risk Management Advisory Committee jointly voted (14 yes, 2 no, 1 abstain) that data support the favorable benefit-risk profile of Spravato (esketamine) nasal spray CIII for adults living with treatment-resistant depression. Spravato is an investigational prescription treatment that is thought to work differently than currently approved therapies for major depressive disorder (MDD). Janssen announced on September 4, 2018 that it submitted a New Drug Application (NDA) to the FDA for the approval of Spravato.1 If approved, Spravato would provide the first new mechanism of action in 30 years to treat this debilitating mental illness.2,3

“We are pleased with the advisory committees’ vote and their recommendation to approve Spravato as a potential therapy for adults living with treatment-resistant depression,” said Husseini K. Manji, M.D., Global Head, Neuroscience Therapeutic Area, Janssen Research & Development, LLC. “Our comprehensive research program for esketamine nasal spray supports a positive benefit-risk profile for adults with treatment-resistant depression.”

The committees based their support on the safety and efficacy data from five Phase 3 studies in patients with treatment-resistant depression: three short-term studies; one maintenance of effect study; and one long-term safety study. In addition, the Spravato research program provided supportive data from three Phase 2 studies and 19 Phase 1 studies in patients with treatment-resistant depression and healthy volunteers. Data from both a short-term Phase 3 study and a long-term Phase 3 study demonstrated that esketamine nasal spray plus a newly initiated oral antidepressant provided statistically significant, clinically meaningful, rapid, and sustained improvement of depressive symptoms in this difficult-to-treat population.4,5 All the patients who participated in the Phase 3 studies received esketamine or placebo in addition to a newly initiated oral antidepressant at the start of the treatment phase.

The long-term safety study showed that esketamine was generally tolerable, with no new safety signals with dosing up to 52 weeks compared to data from short-term (4-week) studies.6 Discontinuation rates due to esketamine-related adverse events were low and occurred typically in the first weeks. Most treatment-emergent adverse events, including dissociative symptoms, dizziness/vertigo, increased blood pressure, and sedation, occurred shortly after dosing while patients were under the supervision of a health care professional, were transient, and resolved the same day. In addition to the comprehensive clinical research program, the company proposed a robust Risk Evaluation and Mitigation Strategy (REMS).

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

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FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression

FDA grants approval for first drug to treat inherited breast cancer

In continuation of my update on olaparib

The U.S. Food and Drug Administration  expanded the approved use of Lynparza (olaparib tablets) to include the treatment of patients with certain types of breast cancer that have spread (metastasized) and whose tumors have a specific inherited (germline) genetic mutation, making it the first drug in its class (PARP inhibitor) approved to treat breast cancer, and it is the first time any drug has been approved to treat certain patients with metastatic breast cancer who have a "BRCA" gene mutation. Patients are selected for treatment with Lynparza based on an FDA-approved genetic test, called the BRACAnalysis CDx.

"This class of drugs has been used to treat advanced, BRCA-mutated ovarian cancer and has now shown efficacy in treating certain types of BRCA-mutated breast cancer," said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types."

Breast cancer is the most common form of cancer in the United States. The National Cancer Institute at the National Institutes of Health estimates approximately 252,710 women will be diagnosed with breast cancer this year, and 40,610 will die of the disease. Approximately 20-25 percent of patients with hereditary breast cancers and 5-10 percent of patients with any type of breast cancer have a BRCA mutation. BRCA genes are involved with repairing damaged DNA and normally work to prevent tumor development. However, mutations of these genes may lead to certain cancers, including breast cancers.

Lynparza is a PARP (poly ADP-ribose polymerase) inhibitor that blocks an enzyme involved in repairing damaged DNA. By blocking this enzyme, DNA inside the cancerous cells with damaged BRCA genes may be less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth. Lynparza was first approved by the FDA in 2014 to treat certain patients with ovarian cancer and is now indicated for the treatment of patients with germline breast cancer susceptibility gene (BRCA) mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, who have been previously treated with chemotherapy. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior hormonal (endocrine) therapy or be considered inappropriate for endocrine treatment.

FDA also expanded the approval of the BRACAnalysis CDx, an approved companion diagnostic to Lynparza, to include the detection of BRCA mutations in blood samples from patients with breast cancer.

The safety and efficacy of Lynparza for the treatment of breast cancer was based on a randomized clinical trial of 302 patients with HER2-negative metastatic breast cancer with a germline BRCA mutation. The trial measured the length of time the tumors did not have significant growth after treatment (progression-free survival). The median progression-free survival for patients taking Lynparza was 7 months compared to 4.2 months for patients taking chemotherapy only.

Common side effects of Lynparza include low levels of red blood cells (anemia), low levels of certain white blood cells (neutropenia, leukopenia), nausea, fatigue, vomiting, common cold (nasopharyngitis), respiratory tract infection, influenza, diarrhea, joint pain (arthralgia/myalgia), unusual taste sensation (dysgeusia), headache, indigestion (dyspepsia), decreased appetite, constipation and inflammation and sores in the mouth (stomatitis).

Severe side effects of Lynparza include development of certain blood or bone marrow cancers (myelodysplastic syndrome/acute myeloid leukemia) and inflammation in the lungs (pneumonitis). Lynparza can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception. Women taking Lynparza should not breastfeed as it could cause harm to a newborn baby.

This application was granted Priority Review, under which the FDA's goal is to take action on an application within 6 months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition.

Lynparza is also approved for the treatment of patients with BRCA-mutated, advanced ovarian cancer who have received three or more treatments of chemotherapy, and for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer whose tumors have completely or partially responded to chemotherapy.

Ref : https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm592347.htm

FDA grants approval for first drug to treat inherited breast cancer