FDA Approves Gattex (teduglutide) for Children 1 Year of Age and Older With Short Bowel Syndrome (SBS)

In continuation of my update on Teduglutide

Takeda Pharmaceuticals, U.S.A., Inc. (“Takeda”), announced  that the U.S. Food and Drug Administration (FDA) approved extending the indication of Gattex(teduglutide) for injection to pediatric patients 1 year of age and older with Short Bowel Syndrome (SBS) who need additional nutrition or fluids from intravenous (IV) feeding (parenteral support).

In children, SBS is a life-threatening, chronic, and rare malabsorption disorder resulting from surgical removal of a large portion of the intestine, which is typically due to congenital or acquired conditions of the newborn or trauma.2-4 Children with SBS are unable to absorb enough nutrients and fluids from what they eat and drink alone.2 A goal of SBS treatment is to restore the remaining intestine’s ability to absorb nutrients and reduce long-term dependence on parenteral support (PS).

“As a pediatric gastroenterologist, one of my main treatment goals for children with SBS is to reduce their dependency on parenteral support,” said Beth Carter, MD, Medical Director of Intestinal Rehabilitation and Nutrition Support, Children’s Hospital Los Angeles. “I’m pleased that patients have access to a medication that may help them reach that goal.”

Gattex is the first and only medicine that mimics naturally occurring glucagon-like peptide-2 (GLP-2), which helps the remaining intestine absorb more nutrients.1 In a pharmacodynamic study in adults, Gattex was shown to improve the amount of fluids absorbed by the intestines.

“Addressing high unmet needs of patients with complex and debilitating gastrointestinal (GI) conditions is a focus of Takeda’s work,” said Andrew Grimm, Global Clinical Development Lead, Takeda. “As the first U.S.-approved therapy in pediatric SBS patients dependent on PS that improves absorption, Gattex offers these patients new hope to reduce PS requirements and the potential for PS independence. This approval underscores Takeda’s commitment to patients with rare and devastating GI conditions like SBS.”

In a 24-week pediatric study, Gattex helped reduce the volume of daily PS required and time spent administering PS. Some children even achieved complete freedom from PS.1 Fifty- nine pediatric patients with SBS aged 1 year through 17 years chose whether to receive Gattex or standard of care (SOC). Patients who chose to receive Gattex treatment were subsequently randomized in a double-blind manner to 0.025 mg/kg/day (n=24) or 0.05 mg/kg/day (n=26), while 9 patients enrolled in the SOC arm. The recommended dosage of Gattex is 0.05 mg/kg/day. Randomization to the Gattex dose groups was stratified by age.

At the end of the 24-week study, 69% of patients (18/26) who took Gattex 0.05 mg/kg each day reduced PS volume by 20% or more. Based on patient-diary data, patients who received Gattex 0.05 mg/kg/day experienced a 42% mean reduction in PS volume (mL/kg/day) from baseline (-23 mL/kg/day from baseline). At week 24, 38% of patients (10/26) were able to reduce PS infusion by at least 1 day per week. Patients reduced their PS infusion time by 3 hours per day on average compared to baseline. In addition, during this study 3 out of 26 (12%) children who received Gattex 0.05 mg/kg/day completely weaned off PS.

Gattex has a demonstrated safety profile that is similar overall in pediatric and adult patients. The most common adverse reactions (≥10%) seen in adult patients treated with Gattex in clinical trials were abdominal pain, nausea, upper respiratory tract infection, abdominal distension, injection site reaction, vomiting, fluid overload, and hypersensitivity

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

FDA Approves Fragmin (dalteparin sodium) as First Anticoagulant for Venous Thromboembolism in Pediatric Patients

    

In continuation of my update on Dalteparin

U.S. Food and Drug Administration,  approved Fragmin (dalteparin sodium) injection, for subcutaneous use, to reduce the recurrence of symptomatic venous thromboembolism (VTE) in pediatric patients one month of age and older. VTE can include deep vein thrombosis (blood clot in the deep veins of the leg) and pulmonary embolism (blood clot in the lungs), which can lead to death.

“Most children who have VTE are fighting a serious underlying primary illness such as cancer or congenital heart disease. Not only are they fighting a serious illness, having a condition like VTE can then lead to significant complications and even death,” 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. “Prior to this approval, there had been no FDA-approved therapies to treat VTE in pediatric patients. Given the unmet need, we granted the Fragmin application priority review and today we are approving it as the first anticoagulant (blood thinner) indicated for pediatric patients. We remain committed to advancing treatments for children with unmet medical needs.”

VTE usually develops as a secondary complication of underlying clinical conditions such as a venous catheter, cancer, infection, congenital heart disease, and trauma or surgery. Pediatric VTE is associated with an increased risk of in-hospital mortality, recurrent VTE and post-thrombotic syndrome (damage to vein).

Fragmin was initially approved by the FDA in 1994 for adults and is a type of heparin, which works as an anticoagulant. The efficacy of Fragmin in children was based on a single trial with 38 pediatric patientswith symptomatic deep vein thrombosis and/or pulmonary embolism. Patients were treated with Fragmin for up to three months, with starting doses by age and weight. At study completion, 21 patients achieved resolution of the qualifying VTE, seven patients showed regression, two patients showed no change, no patients experienced progression of the VTE and one patient experienced recurrence of VTE.

Common side effects of patients taking Fragmin are bleeding, including hemorrhage (heavy discharge of blood from a blood vessel), thrombocytopenia (low blood platelet count), hematoma (collection of blood) or pain at the injection site and transient elevation of transaminases (elevated level of liver enzymes).

Health care professionals are advised to use caution in conditions with increased risk of hemorrhage and monitor thrombocytopenia of any degree closely. Health care professionals are warned not to use benzyl alcohol preservative multiple-dose formulations in infants as they contain benzyl alcohol and should not be used. Patients are advised to have blood count laboratory tests periodically. Health care professionals are advised to monitor patients closely for bleeding when administering Fragmin to patients who currently take anticoagulants. Patients at risk for VTE may receive certain treatments or interventions to help reduce the likelihood of the formation of blood clots (known as thromboprophylaxis), including taking anticoagulants.

The label for Fragmin contains a boxed warning to alert health care professionals and patients that epidural or spinal hematomas (accumulation of blood that can mechanically compress the spinal cord) may occur in patients who are anticoagulated due to taking certain medications called low molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia (injection near the spine) or undergoing spinal puncture (removing spinal fluid for testing). These hematomas may result in long-term or permanent paralysis. Health care professionals are advised to consider these risks when scheduling patients for spinal procedures as patients may be at a higher risk of developing VTE. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters, use of other drugs that affect hemostasis at the same time when using Fragmin, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors and other anticoagulants; history of traumatic or repeated epidural or spinal punctures; and a history of spinal deformity or surgery. The optimal timing between the administration of Fragmin and neuraxial procedures is not known. Health care professionals are advised to monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Health care professionals are advised to consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.

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

https://www.drugbank.ca/drugs/DB06779

FDA Approves Revlimid (lenalidomide) In Combination with Rituximab for the Treatment of Adult Patients with Previously Treated Follicular Lymphoma or Marginal Zone Lymphoma

In continuation of my update on lenalidomide

Celgene Corporation,  announced the U.S. Food and Drug Administration (FDA) approved Revlimid (lenalidomide) in combination with a rituximab product (R²) for the treatment of adult patients with previously treated follicular lymphoma (FL) or marginal zone lymphoma (MZL) following Priority Review designation. This is the first FDA-approved combination treatment regimen for patients with these indolent forms of non-Hodgkin’s lymphoma (NHL) that does not include chemotherapy.

“Nearly 15 years following the initial FDA approval, Revlimid continues to demonstrate benefits for new patient populations,” said Jay Backstrom, M.D., M.P.H., Chief Medical Officer for Celgene. “Revlimid in combination with rituximab (R2) leads to immune-mediated treatment effects and represents a chemotherapy-free treatment option that can help patients with previously treated follicular lymphoma and marginal zone lymphoma delay disease progression.”

Immune dysfunction (meaning the immune system is not functioning optimally) is a defining aspect of indolent forms of NHL, including FL and MZL.1,2 When this dysfunction occurs, lymphocytes in the immune system either fail to detect or target cancerous cells.1,2

“Chemotherapy continues to be a standard of care for indolent forms of NHL, but most patients will relapse or become refractory to their current treatment,” said Meghan Gutierrez, Chief Executive Officer for the Lymphoma Research Foundation. “This approval represents a new therapeutic option for previously treated patients with follicular and marginal zone lymphomas, including those who relapse or no longer respond to initial treatment. We commend the patients and scientists who participated in the clinical study for advancing lymphoma research and treatment.”

The approval of R2 is based primarily on results from the randomized, double-blind, Phase 3 AUGMENT study, which evaluated the efficacy and safety of the R² combination versus rituximab plus placebo in patients with previously treated FL (n=295) and MZL (n=63).

In the AUGMENT study, treatment with R2 demonstrated a statistically significant improvement in the primary endpoint of progression-free survival (PFS), evaluated by an independent review committee, versus rituximab-placebo. The median PFS was 39.4 months for patients treated with R2 and 14.1 months for those treated with rituximab-placebo (HR: 0.46; 95% CI, 0.34-0.62; P<0.0001). Median follow-up time was 28.3 months (range, 0.1-51.3) in the intent to treat population (n=358). Although not statistically powered to detect a difference in overall survival, a numeric trend for improvement in overall survival (a secondary endpoint) was also seen with R2 versus rituximab-placebo (16 vs. 26 deaths) (HR: 0.61; 95% CI, 0.33-1.13).

Revlimid is only available through a restricted distribution program called Revlimid REMS® program. Revlimid has a boxed warning for embryo-fetal toxicity, hematologic toxicity, and venous and arterial thromboembolism. Adverse reactions reported in ≥15% of patients with FL/MZL treated with R2 were: neutropenia (58%), diarrhea (31%), constipation (26%), cough (24%), fatigue (22%), rash (22%), pyrexia (21%), leukopenia (20%), pruritus (20%), upper respiratory tract infections (18%), abdominal pain (18%), anemia (16%), headache (15%), thrombocytopenia (15%).

A Marketing Authorization Application for R2 is currently under review by the European Medicines Agency for the treatment of relapsed/refractory FL and MZL. A supplemental new drug application was also submitted to the Japanese Pharmaceuticals and Medical Devices Agency for an additional indication as well as dosage and administration updates for lenalidomide in combination with rituximab for the treatment of relapsed/refractory indolent B-cell NHL.

FDA Approves Sorilux for Adolescent Plaque Psoriasis

In continuation of my update on Sorilux(calcipotriene) 

 

Mayne Pharma Group Limited, announced that the US Food and Drug Administration (FDA) has approved Sorilux(calcipotriene) Foam, 0.005% in adolescents.

Sorilux is now approved for treating plaque psoriasis of the scalp and body in patients aged 12 years and older.

The FDA approved Sorilux in 2010 based on evidence from two 8-week placebo controlled clinical trials in patients with mild to moderate plaque psoriasis of the body and one 8-week placebo controlled clinical trial in patients with moderate plaque psoriasis of the scalp. Further data was obtained in a follow-on open label study in patients aged 12 to 17 years of age with psoriasis.

Sorilux Foam contains calcipotriene, a synthetic vitamin D analog that has a similar receptor binding affinity as natural vitamin D. The exact mechanism of action contributing to the clinical efficacy is unknown.

Psoriasis is a chronic disease of the immune system affecting approximately 7.5 million Americans each year[1]. The most common form, plaque psoriasis affects roughly 80 percent of people who have the condition.

Mayne Pharma's CEO, Mr Scott Richards, said "Sorilux is an elegant foam formulation that is marketed by Mayne Pharma's Specialty Brands sales team alongside recently launched LEXETTE™ (halobetasol propionate) Foam, a potent topical corticosteroid also used to treat plaque psoriasis in adult patients. Topical products are the mainstay of treatment for plaque psoriasis patients and the foam delivery platform has a well-established reputation with dermatologists due to ease of application and lack of greasiness and stickiness, especially in hair-bearing areas and under clothing."

Mayne Pharma directly markets more than 60 products in the US including four branded dermatology products FABIOR® (tazarotene) Foam, Sorilux Foam, DORYX® MPC (doxycycline hyclate) delayed-release tablets and LEXETTE Foam. The Company also markets TOLSURA® (SUBA®-itraconazole) capsules used to treat certain fungal infections which was recently approved and launched this year.

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

FDA Approves Piqray (alpelisib) as First PI3K Inhibitor for Breast Cancer

U.S. Food and Drug Administration approved Piqray (alpelisib) tablets, to be used in combination with the FDA-approved endocrine therapy fulvestrant, to treat postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer (as detected by an FDA-approved test) following progression on or after an endocrine-based regimen.

The FDA also approved the companion diagnostic test, therascreen PIK3CA RGQ PCR Kit, to detect the PIK3CA mutation in a tissue and/or a liquid biopsy. Patients who are negative by the therascreen test using the liquid biopsy should undergo tumor biopsy for PIK3CA mutation testing.

“Piqray is the first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer. The ability to target treatment to a patient’s specific genetic mutation or biomarker is becoming increasingly common in cancer treatment, and companion diagnostic tests assist oncologists in selecting patients who may benefit from these targeted treatments,” 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. “For this approval, we employed some of our newer regulatory tools to streamline reviews without compromising the quality of our assessment. This drug is the first novel drug approved under the Real-Time Oncology Review pilot program. We also used the updated Assessment Aid, a multidisciplinary review template that helps focus our written review on critical thinking and consistency and reduces time spent on administrative tasks.”

Metastatic breast cancer is breast cancer that has spread beyond the breast to other organs in the body (most often the bones, lungs, liver or brain). When breast cancer is hormone-receptor positive, patients may be treated with anti-hormonal treatment (also called endocrine therapy), alone or in combination with other medicines, or chemotherapy.

The efficacy of Piqray was studied in the SOLAR-1 trial, a randomized trial of 572 postmenopausal women and men with HR-positive, HER2-negative, advanced or metastatic breast cancer whose cancer had progressed while on or after receiving an aromatase inhibitor. Results from the trial showed the addition of Piqray to fulvestrant significantly prolonged progression- free survival (median of 11 months vs. 5.7 months) in patients whose tumors had a PIK3CA mutation.

Common side effects of Piqray are high blood sugar levels, increase in creatinine, diarrhea, rash, decrease in lymphocyte count in the blood, elevated liver enzymes, nausea, fatigue, low red blood cell count, increase in lipase (enzymes released by the pancreas), decreased appetite, stomatitis, vomiting, weight loss, low calcium levels, aPTT prolonged (blood clotting taking longer to occur than it should), and hair loss.

Health care professionals are advised to monitor patients taking Piqray for severe hypersensitivity reactions (intolerance). Patients are warned of potentially severe skin reactions (rashes that may result in peeling and blistering of skin or mucous membranes like the lips and gums). Health care professionals are advised not to initiate treatment in patients with a history of severe skin reactions such as Stevens-Johnson Syndrome, erythema multiforme, or toxic epidermal necrolysis. Patients on Piqray have reported severe hyperglycemia (high blood sugar), and the safety of Piqray in patients with Type 1 or uncontrolled Type 2 diabetes has not been established. Before initiating treatment with Piqray, health care professionals are advised to check fasting glucose and HbA1c, and to optimize glycemic control. Patients should be monitored for pneumonitis/interstitial lung disease (inflammation of lung tissue) and diarrhea during treatment. Piqray must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks.

Piqray is the first new drug application (NDA) for a new molecular entity approved under the Real-Time Oncology Review (RTOR) pilot program, which permits the FDA to begin analyzing key efficacy and safety datasets prior to the official submission of an application, allowing the review team to begin their review and communicate with the applicant earlier. Piqray also used the updated Assessment Aid (AAid), a multidisciplinary review template intended to focus the FDA’s written review on critical thinking and consistency and reduce time spent on administrative tasks. 

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

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

FDA Approves Jakafi (ruxolitinib) for the Treatment of Patients with Acute Graft-Versus-Host Disease

In continuation of my update  on ruxolitinib

Incyte Corporation   announced that the U.S. Food and Drug Administration (FDA) has approved Jakafi (ruxolitinib) for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older. Jakafi is the first and only FDA-approved treatment for this indication.

“For the first time, patients with steroid-refractory acute GVHD, and the physicians that treat them, have an FDA-approved treatment for this serious disease,” stated Hervé Hoppenot, Chief Executive Officer, Incyte. “This approval is also an important milestone for Incyte, as it marks the third indication for Jakafi in the United States, further underscoring Incyte’s commitment to delivering innovative medicines for patients in need. We are proud of the impact Jakafi has had on patients’ lives to-date and are dedicated to advancing our ongoing research in JAK inhibition to serve more GVHD patients in the future.”

The approval was based on data from REACH1, an open-label, single-arm, multicenter study of Jakafi in combination with corticosteroids in patients with steroid-refractory grade II-IV acute GVHD. Of the 71 patients recruited into REACH1, 49 patients were refractory to steroids alone, 12 patients had received two or more prior anti-GVHD therapies and 10 patients did not otherwise meet the FDA definition of steroid-refractory. Jakafi was administered at 5 mg twice daily, and the dose could be increased to 10 mg twice daily after three days in the absence of toxicity.

The efficacy of Jakafi was evaluated based upon Day 28 overall response rate (ORR), defined as a complete response (CR), very good partial response or partial response based on the Center for International Blood and Marrow Transplant Research (CIBMTR) criteria. The Day 28 ORR in the 49 patients refractory to steroids alone was 57 percent with a CR rate of 31 percent. The most frequently reported adverse reactions among all 71 study participants were infections (55 percent) and edema (51 percent), and the most common laboratory abnormalities were anemia (75 percent), thrombocytopenia (75 percent) and neutropenia (58 percent).

GVHD is a condition that can occur after an allogeneic stem cell transplant (the transfer of stem cells from a donor) where the donated cells initiate an immune response and attack the transplant recipient’s organs, leading to significant morbidity and mortality. There are two major forms of GVHD, acute and chronic, that can affect multiple organ systems including the skin, gastrointestinal (digestive) tract and liver. Patients who develop steroid-refractory acute GVHD can progress to severe disease, with one-year mortality rates of approximately 70 percent.1

“Every year in the United States, about half of the people who develop acute GVHD do not respond adequately to steroids, making it an extremely challenging disease to treat,” said Madan Jagasia, M.B.B.S., M.S., M.M.H.C., a lead investigator on the REACH1 trial and Professor of Medicine, Vanderbilt University Medical Center, Department of Medicine, Division of Hematology-Oncology and Chief Medical Officer, Vanderbilt-Ingram Cancer Center. “While allogeneic stem cell transplants have the potential to transform people’s lives, the onset of acute GVHD can significantly impact their prognosis. I am excited that we now have Jakafi as a new treatment option for acute GVHD patients that do not respond to corticosteroids who, until now, have had limited choices.”

Previously, the FDA granted Jakafi Breakthrough Therapy Designation and Orphan Drug Designation for the treatment of patients with steroid-refractory acute GVHD, and the supplemental New Drug Application (sNDA) was reviewed under the FDA’s Priority Review program.

Jakafi will be made available to appropriate patients with steroid-refractory acute GVHD immediately. Incyte is committed to supporting patients and removing barriers to access medicines. Eligible patients in the U.S. who are prescribed Jakafi have access to IncyteCARES (Connecting to Access, Reimbursement, Education and Support), a comprehensive program offering patient support, including financial assistance and ongoing education and resources to eligible patients.

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

Ocular Therapeutix Announces FDA Approval of Dextenza (dexamethasone intracanalicular insert) for the Treatment of Ocular Inflammation Following Ophthalmic Surgery

In continuation of my update on Dextenza 

Ocular Therapeutix™, Inc. ), a biopharmaceutical company focused on the formulation, development, and commercialization of innovative therapies for diseases and conditions of the eye,   announced the U.S. Food and Drug Administration (FDA) approved a Supplemental New Drug Application (sNDA) for Dextenza to include the treatment of ocular inflammation following ophthalmic surgery as an additional indication. With the approval of the sNDA, Dextenza is now approved for the treatment of both ocular inflammation and pain following ophthalmic surgery.

Dextenza is the first FDA-approved intracanalicular insert, a novel route of administration that delivers drug to the surface of the eye without the need for eye drops. Dextenza is a preservative-free, resorbable hydrogel insert that delivers 0.4mg of dexamethasone to treat post-surgical ocular inflammation and pain for up to 30 days with a single administration. Dextenza originally received FDA approval in November 2018 for the treatment of ocular pain following ophthalmic surgery.

“We could not be more excited about both the approval and its earlier-than-expected timing,” said Antony Mattessich, the Company’s President and Chief Executive Officer. “With our C-Code and pass-through payment status effective on July 1, the expanded indication gives us tremendous momentum as we approach our commercial launch.”

The approval of the sNDA is supported by three Phase 3 randomized, vehicle-controlled trials; patients received Dextenza or a vehicle immediately upon completion of cataract surgery. In all three trials, Dextenza had, at a statistically significant level, a higher proportion of patients than the vehicle group who were pain free on post-operative Day 8. On post-operative Day 14, in two of the three studies, Dextenza had a higher proportion of patients than the vehicle group, at a statistically significant level, who had an absence of anterior chamber cells.

http://www.chemdiv.com/dextenza-dexamethasone-ophthalmic-insert-first-intracanalicular-insert-drug-delivery/

AMAG Pharmaceuticals Announces FDA Approval of Vyleesi (bremelanotide injection) for Hypoactive Sexual Desire Disorder (HSDD) in Premenopausal Women

In continuation of my update on  bremelanotide

MAG Pharmaceuticals, Inc.    announced  that the U.S. Food and Drug Administration (FDA) has approved Vyleesi (bremelanotide injection), a melanocortin receptor agonist, to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. The Vyleesi autoinjector is the first treatment for this patient population that can be self-administered as needed in anticipation of sexual activity.

HSDD is characterized by low sexual desire that causes distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance.

“HSDD has been recognized as a medical condition since the 1970s, yet it has been widely underdiagnosed and undertreated,” said Anita H. Clayton, M.D., Chair, Department of Psychiatry & Neurobehavioral Sciences, University of Virginia School of Medicine, VA. “Women with HSDD often avoid situations that could lead to intimacy, the impact of which goes far beyond the bedroom and can often result in anxiety, loss of vitality, self-esteem issues and relationship stress. It is important that women suffering with this condition have a choice of treatment options available to them.”

HSDD is thought to have a neurobiologic basis which is supported by brain imaging studies. When study participants were shown visual sexual stimuli, there was a difference in the brain activation patterns between women with HSDD compared to those women without HSDD[i].

“Today’s approval underscores AMAG’s commitment to women’s health and dedication to raising awareness and improving education about HSDD,” said Julie Krop, M.D., chief medical officer at AMAG. “While HSDD is the most common female sexual dysfunction condition, it is largely under-recognized. I want to thank the thousands of women who participated in the clinical trials to support the approval of Vyleesi. Their participation in the trials helped to pave the way for a novel treatment option that offers hope to the nearly six million premenopausal women who have suffered in silence from HSDD—empowering them to reclaim their sexual desire.”

The FDA approval of Vyleesi is based upon data from approximately 1,200 women in two pivotal, double-blind placebo controlled Phase 3 trials (RECONNECT). In both clinical trials, Vyleesi met the pre-specified co-primary efficacy endpoints of improvement in desire and reductions in distress as measured by validated patient-reported outcome instruments. Upon completion of the trial, women had the option to continue in a voluntary open-label safety extension study for an additional 12 months. Nearly 80 percent of patients who completed the Phase 3 trials elected to remain in the open-label portion of the study, where all of these patients received Vyleesi.

In the pivotal trials, the most common adverse events were nausea, flushing, injection site reactions, and headache. The majority of events were reported to be transient and mild-to-moderate in intensity. In clinical trials, Vyleesi caused small, transient increases in blood pressure, and is contraindicated in women with uncontrolled high blood pressure or known cardiovascular risk.

AMAG is committed to working with payers and healthcare professionals to help ensure women with HSDD have access to Vyleesi. The product will be commercially available in September through select specialty pharmacies. To raise healthcare provider awareness of Vyleesi, AMAG will leverage its existing women’s and maternal health sales force of approximately 125 sales representatives calling on U.S. obstetrics, gynecologists and sexual medicine specialists, and will also offer patients the ability to connect with a physician through a telemedicine option. Patients and providers can learn more about HSDD and Vyleesi at www.vyleesi.com and sign up to receive information about how to obtain Vyleesi as soon as it is available.

AMAG in-licensed Vyleesi from Palatin Technologies, Inc. in February 2017. Under the terms of the agreement, the approval of Vyleesi by the FDA triggers a $60 million payment obligation to Palatin. In addition, AMAG will pay Palatin tiered royalties on annual net sales of Vyleesi ranging from the high-single digits to the low double-digits. AMAG will also pay Palatin sales milestones based on escalating annual net sales thresholds, the first of which is $25 million, triggered at annual net sales of $250 million.

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

FDA Approves Expanded Use of Vraylar (cariprazine) in the Treatment of Bipolar Depression

In continuation of my update on Cariprazine

Allergan plc (NYSE: AGN) and Gedeon Richter Plc.   announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for Vraylar (cariprazine) for expanded use to treat depressive episodes associated with bipolar I disorder (bipolar depression) in adults. Vraylar is also approved in the U.S. to treat manic or mixed episodes associated with bipolar I disorder in adults. There are nearly 11 million adults in the U.S. living with bipolar disorder, a condition that causes extreme shifts in mood, energy, and activity levels.

"Treating bipolar disorder can be very difficult because people living with the illness experience a range of depressive and manic symptoms, sometimes both at the same time, and this FDA approval gives healthcare providers a new option to treat the full spectrum of bipolar I disorder symptoms, specifically manic, mixed, and depressive episodes, with just one medication," said Dr. Stephen Stahl, Professor of Psychiatry at the University of California San Diego and lead author of the post hoc analysis, Cariprazine Efficacy in Patients with Bipolar Depression and Concurrent Manic Symptoms. "Treating depression, mania and mixed episodes with a single medication is important for people living with, and healthcare providers treating, this complex illness. This approval can streamline a treatment decision while helping to stabilize the disorder."

Seventy percent of people living with bipolar disorder receive at least one misdiagnosis and consult an average of four doctors over approximately 10 years before being accurately diagnosed.3 Many patients take multiple medications to treat the symptoms of this condition.

The FDA approval for the expanded indication of Vraylar is based on three pivotal trials, including RGH-MD-53, RGH-MD-54 and RGH-MD-56, in which cariprazine demonstrated greater improvement than placebo for the change from baseline to week six on the Montgomery Asberg Depression Rating scale (MADRS) total score. In all three studies, the Vraylar 1.5 mg dose demonstrated statistical significance over placebo; additionally, in RGH-MD-54, the Vraylar 3 mg dose demonstrated statistical significance over placebo. Common adverse events reported in the pivotal trials were nausea, akathisia, restlessness, and extrapyramidal symptoms.

"This approval represents an important milestone in our efforts to help patients and prescribing healthcare providers effectively manage bipolar I disorder and demonstrates our ongoing focus on mental health," said David Nicholson, Chief Research & Development Officer at Allergan.  "We are committed to developing therapies for complex mental health disorders, including Vraylar, which is currently in Phase 3 clinical trials for the treatment of major depressive disorder."

"This approval is considered a notable achievement in the development process of cariprazine, our flagship product," said Dr. István Greiner, Research Director of Gedeon Richter Plc. "We are pleased that more and more patient groups suffering from psychiatric disorders will get access to cariprazine as a treatment option."

About Vraylar (cariprazine)

Vraylar is an oral, once daily atypical antipsychotic approved for the acute treatment of adults with manic or mixed episodes associated with bipolar I disorder (3 to 6 mg/day) and for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults (1.5 or 3 mg/day). Vraylar is also approved for the treatment of schizophrenia in adults (1.5 to 6 mg/day).

While the mechanism of action of Vraylar is unknown, the efficacy of Vraylar could be mediated through a combination of partial agonist activity at central dopamine D₂ and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors. Pharmacodynamic studies with cariprazine have shown that it acts as a partial agonist with high binding affinity at dopamine D3, dopamine D2, and serotonin 5-HT1A receptors. Cariprazine demonstrated up to ~8-fold greater in vitro affinity for dopamine D3 vs D2 receptors. Cariprazine also acts as an antagonist at serotonin 5-HT2B and 5-HT2A receptors with high and moderate binding affinity, respectively as well as it binds to the histamine H1 receptors.

Vraylar shows lower binding affinity to the serotonin 5-HT2C and α1A- adrenergic receptors and has no appreciable affinity for cholinergic muscarinic receptors. The clinical significance of these in vitro data is unknown.

Vraylar was discovered and co-developed by Gedeon Richter Plc and is licensed by Allergan, in the U.S. and Canada. For more than a decade both companies have conducted over 20 clinical trials enrolling thousands of patients worldwide to evaluate the efficacy and safety of cariprazine for people living with a broad range of mental health illnesses.

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

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

      

         Ceftolozane/tazobactam                                                           Tazobactam                                                

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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