Dosage breakthrough for schizophrenia drug, plus 5 more FDA approvals

June 2, 2015

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FDA approvals for the first week of June 2015.

FDA has approved the first and only 4-times-per-year schizophrenia drug.

Three-month paliperidone palmitate (Invega Trinza, Janssen Pharmaceuticals) injection, atypical antipsychotic was approved under priority review. Before starting Invega Trinza, patients must be adequately treated with 1-month paliperidone palmitate (Invega Sustenna) for at least 4 months.

Schizophrenia affects approximately 2.4 million adults and is a complex and chronic brain disorder in which symptoms can be severe and disabling and can affect all aspects of a person’s daily life. The course of schizophrenia is varied, frequently involving periodic relapses of the disease with sometimes incomplete response to treatment. Each relapse can result in reduced response to treatment, putting continued symptom control even further out of reach.

In a long-term maintenance trial, 93% of patients treated with Invega Trinza did not experience a significant return of schizophrenia symptoms. The results of the phase 3 study were published in March by JAMA Psychiatry. Based on positive efficacy, Janssen concluded this study early following the recommendation of an Independent Data Monitoring Committee (IDMC).

“While there is no cure for schizophrenia Invega Trinza may allow people living with this condition and their treatment teams to spend more time focusing on aspects of their treatment plan such as recovery progress and less time having medication conversations,” said Robyn Frenze, Janssen spokesperson. “With this new treatment option, healthcare providers can also give patients greater independence by enabling them to focus less on taking their medication and more on other aspects of their treatment plan.”

For most people with schizophrenia, the clinical course of the disease is defined by periods of stabilization and relapse; 75% of people with schizophrenia will have a relapse.

“Treatment-related issues, such as adherence problems and treatment interruption/delay, have been identified as potential drivers of relapse,” said Frenze. “With long-acting therapy that is professionally administered, healthcare provdiers can know that medication is on board when patients receive their medication as scheduled.”

Relapse of schizophrenia symptoms, which can result from poor adherence to otherwise effective antipsychotic medication, may lead to treatment resistance, she said. Patients with schizophrenia commonly lack insight into their disease and the importance of medication, compromising treatment adherence.

“Professionally administered long-acting injectable antipsychotic treatments eliminate the need for daily dosing, thus helping to address the problem of nonadherence with daily medications,” Frenze said.

Mental health recovery is an ongoing process, not a single outcome. Each person’s recovery experience is unique. The recovery process can include treatment such as counseling and rehabilitation therapy. These programs, combined with medication, may help delay time to relapse. By following a treatment plan and taking medicine as prescribed, people living with schizophrenia can work toward the recovery process.

Once available, the list price of Invega Trinza will be at parity to that of Invega Sustenna monthly treatment. It is anticipated that Invega Trinza will be commercially available by mid-June.

NEXT: Drug approved for rare lung disease that strikes younger women

FDA approved sirolimus (Rapamune, Pfizer) to treat lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease that primarily affects women of childbearing age.

Rapamune is an immunosuppressant agent, available as a tablet and an oral solution.

LAM is characterized by an uncontrollable growth of smooth muscle cells within lung tissue, including the airways, blood vessels, and lymph vessels. The abnormal cells produce materials that break down tissue causing the formation of cysts, which destroy the architecture of the lungs and limit the delivery of oxygen to the rest of the body. Approximately 800 patients in the United States are currently diagnosed with LAM, which is often fatal.

The drug acts to improve lung function in women by inhibiting T-cell activation and proliferation in response to antigenic stimulation while also inhibiting antibody production.

It was originally approved in 1999 to help prevent organ rejection in patients aged 13 years and older receiving kidney transplants. FDA granted Rapamune breakthrough therapy designation and priority review for LAM due to sponsor demonstration that the drug may offer a substantial improvement over available therapies. The drug also received orphan drug designation.

FDA's approval of Rapamune is based on the results from the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus or MILES Trial that compared Rapamune to placebo in 89 patients for a 1-year treatment period, followed by a 1-year observation period. The trial studied the difference between the groups in forced expiratory volume in 1 second (FEV₁) The difference between the groups in the average decrease in FEV₁ was approximately 153 mL.

Mouth and lip ulcers, diarrhea, abdominal pain, nausea, and sore throat are the most common side effects associated with Rapamune in the treatment of LAM include. Serious side effects including hypersensitivity and edema have been observed in renal transplant patients.

NEXT: Once-daily maintenance combo drug approved for COPD

FDA approved once-daily tiotropium bromide and olodaterol (Stiolto Respimat, Boehringer Ingelheim) Inhalation Spray as a long-term, once-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

Stiolto is administered via Respimat, the platform inhaler for the Boehringer Ingelheim respiratory therapies, including approved and investigational therapies.

Stiolto Respimat is not indicated to treat asthma or acute deterioration of COPD. COPD, which includes chronic bronchitis and emphysema, is a serious but treatable lung disease. More than 15 million Americans have been told that they have COPD, but as many as 45% of the total estimated COPD cases in the United States remain undiagnosed. Patients are typically diagnosed when lung function is already significantly impaired. COPD symptoms can negatively impact a patient’s ability to breathe especially when performing daily activities.

This combination therapy includes tiotropium, the active ingredient in Spiriva- the number 1 prescribed COPD maintenance therapy in the United States-and olodaterol, the active ingredient in Striverdi.

“We believe patients may appreciate the benefits of a maintenance medication that improves lung function within 5 minutes, lasts all day and reduces the use of rescue inhalers,” said Boehringer Ingelheim’s vice president of respiratory clinical development & medical affairs Danny McBryan, MD.

Respimat actively delivers a slow-moving mist that helps patients inhale the medication.

Stiolto Respimat significantly improved lung function compared with either drugs alone in clinical trials involving more than 5,000 patients according to the FDA. Nasopharyngitis, cough, and back pain were the most common adverse reactions reported.

Further, Stiolto Respimat is proven to be more effective than either Spiriva Respimat or olodaterol alone, with a comparable safety profile, according to Dr McBryan.

NEXT: First concentrated mealtime insulin analog approved

FDA approved Eli Lilly’s Humalog 200 units/mL KwikPen (insulin lispro 200 units/mL; U-200), the company announced on May 27.

The Humalog U-200 KwikPen (insulin lispro 100 units/mL) marks the first FDA approval of a concentrated mealtime insulin analog. The KwikPen holds twice as many units of insulin (600 units vs. 300 units) as the U-100 formulation in the same 3-mL cartridge, offering patients “a pen that lasts longer between pen changes, allowing for fewer changes every month,” according to Eli Lilly.

Humalog U-200 KwikPen delivers the same dose in half the volume of Humalog U-100 KwikPen with no dose conversions required, and can be dialed in 1-unit increments to a maximum of 60 units per injection.

"Diabetes is a progressive disease that often requires increased doses of insulin over time to better control a patient's blood sugar levels," said David Kendall, MD, vice president of Medical Affairs for Lilly Diabetes. "Humalog U-200 KwikPen represents a new option for people with diabetes. Fewer pen changes per month may help people who require higher daily doses of mealtime insulin better fit their treatment in their daily lives."

Approval was based on a demonstration of the bioequivalence of Humalog 200 units/mL relative to Humalog 100 units/mL in a pharmacokinetic/pharmacodynamic study.

FDA's. approval follows the approval of Humalog 200 units/mL KwikPen in the European Union in October, 2014.

The most common side effect of Humalog is hypoglycemia (low blood sugar), which may be severe and cause unconsciousness, seizures and death. Other possible adverse events include generalized allergies and anaphylaxis, hypokalemia, fluid retention and heart failure with concomitant use of PPAR-gamma agonists, and hyperglycemia and ketoacidosis due to insulin pump device malfunction.

NEXT: FDA approves 2 new IBS-D treatments

FDA approved 2 new treatments for adults who have irritable bowel syndrome with diarrhea (IBS-D), eluxadoline (Viberzi) and rifaximin (Xifaxan).

Eluxadoline is manufactured by Patheon Pharmaceuticals Inc., Cincinnati, Ohio, and distributed by Forest Pharmaceuticals Inc., a subsidiary of Forest Laboratories, LLC, Cincinnati. Rifaximin is marketed by Salix Pharmaceuticals, Inc., Raleigh, N.C.

Studies estimate that IBS affects up to 15% of adults in the United States. IBS-D is known as a subtype with diarrhea occurring a quarter of time or more.

“For some people, IBS can be quite disabling, and no one medication works for all patients suffering from this gastrointestinal disorder,” said Julie Beitz, MD, director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research. “The approval of two new therapies underscores the FDA’s commitment to providing additional treatment options for IBS patients and their doctors.”

Eluxadoline is taken an oral agent with a new active ingredient. Patients should be instructed to take the medicine twice daily with food. Eluxadoline activates receptors in the nervous system that can lessen bowel contractions.

Rifaximin, another oral medication, can be taken three times a day for 14 days, for the treatment of abdominal pain and diarrhea in individuals with IBS-D. Patients who experience a recurrent symptoms can be retreated with a 14-day treatment course, up to two times.

An antibiotic derived from rifampin, rifaximin was previously approved as treatment for travelers’ diarrhea caused by E coli and for reduction of the risk in adult patients of recurring overt hepatic encephalopathy. The exact mechanism of action of rifaximin for treatment of IBS-D is not known, but is thought to be related to changes in the bacterial content in the gastrointestinal tract.

The safety and effectiveness of eluxadoline for treatment of IBS-D were established in 2 double-blind, placebo-controlled clinical trials in which more than 2,400 patients were randomly assigned to receive eluxadoline or placebo. Results showed eluxadoline was more effective in simultaneously reducing abdominal pain and improving stool consistency than placebo over 26 weeks of treatment.

The safety and effectiveness of rifaximin was established in 3 double-blind, placebo-controlled trials. In the first 2 trials, more than 1,250 patients were randomly assigned to receive rifaximin or placebo for 14 days, and then followed for a 10-week treatment-free period. More rifaximin-treated patients reported improvements in abdominal pain and stool consistency than those in the placebo group.

A third trial evaluated repeat courses of rifaximin, because patients with IBS-D can develop recurrent signs and symptoms after a single treatment course of rifaximin. A total of 636 patients with recurrent symptoms of IBS-D were randomly assigned to receive either rifaximin or placebo for 2 additional 14-day courses separated by 10 weeks. More patients treated with rifaximin than placebo noted relief in abdominal pain and better stool consistency in this phase of the study.