- FDA Approves New Hepatitis C Medication: Vosevi®
- FDA Approves Two New ADHD Drugs: Cotempla XR-ODT® and Mydayis®
- Orencia® Now Indicated for Psoriatic Arthritis
- Risk of Meningococcal Disease with Soliris®
- FDA Approval and Launch of Second Biosimilar to Remicade®
- FDA Advisory Panel Votes in Favor of First CAR-T Cell Therapy
- Pfizer Drug Shortage Update
- Discontinuation of Seizure Drug and Antibiotic
New Specialty Drug Approvals
FDA Approves New Hepatitis C Medication: Vosevi®
In July 2017, the U.S. Food & Drug Administration (FDA) approved a new fixed-dose combination medication for the treatment of chronic hepatitis C virus (HCV): Vosevi®. Vosevi is a combination of three anti-viral medications: sofosbuvir, velpatasvir, voxilaprevir. Vosevi is approved for the treatment of adult patients with chronic HCV infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). It is specifically indicated for patients who have genotype 1, 2, 3, 4, 5 or 6 infection and have been previously treated with an HCV regimen containing an NS5A inhibitor (such as, daclatasvir [Daklinza®], elbasvir [found in Zepatier®], ledipasvir [found in Harvoni®], ombitasvir [found in Technivie®], or velpatasvir [found in Epclusa®]). It is also indicated for patients with genotype 1a or 3 infection who have previously received treatment with an HCV regimen containing sofosbuvir without an NS5A inhibitor. These prior regimens include sofosbuvir with or without: peginterferon alfa/ribavirin, ribavirin, boceprevir, simeprevir, or teleprevir.
This approval marks the first therapy specifically for patients who have received prior treatment with a direct-acting antiviral drug such as sofosbuvir (Sovaldi®). The safety and efficacy of Vosevi were determined in two phase III clinical studies evaluating 750 adults without cirrhosis or with compensated cirrhosis. In these trials, 96% to 97% of patients who received Vosevi had no detectable virus found 12 weeks (SVR-12) after completing therapy. SVR-12 is considered a surrogate marker for cure of the HCV infection. Patients enrolled in these trials had previously failed treatment with an NS5A inhibitor or sofosbuvir.
Similar to other HCV drugs, Vosevi carries a black box warnings regarding the risk for hepatitis B reactivation in patients coinfected with hepatitis B virus (HBV) and HCV. As a result, it is recommended that all patients be tested for HBV infection prior to starting therapy. Vosevi is contraindicated in combination with rifampin and carries a warning/precaution for slowed heart rate in patients receiving the anti-arrhythmia drug amiodarone. The most common side effects observed in clinical trials were headache, fatigue, diarrhea, and nausea.
Vosevi is supplied as a fixed-dose combination tablet containing 400 mg of sofosbuvir, 100 mg of velpatasvir, and 100 mg of voxilaprevir with an average wholesale price (AWP) of $1,068 per each oral tablet. The recommended dose of Vosevi is one tablet orally once daily with food for 12 weeks. NPS is planning to review Vosevi for placement on the national formularies. For additional information please view the FDA press release or product prescribing information.
New Drug Approvals
FDA Approves Two New ADHD Drugs: Cotempla XR-ODT® and Mydayis®
In June 2016, the U.S. FDA approved a new formulation of methylphenidate extended-release: Cotempla® XR-ODT. The new orally-disintegrating extended-release tablets are indicated for the treatment of attention deficit hyperactive disorder (ADHD) in patients 6 to 17 years old. Cotempla XR-ODT is the first methylphenidate extended-release orally-disintegrating tablet to receive FDA approval. A phase III study conducted in children demonstrated significant improvements in ADHD symptoms with Cotempla XR-ODT compared to placebo. Symptom control was observed at 1-hour post-dose with a duration of up to 12 hours, and no serious adverse events were observed. Cotempla XR-ODT is a schedule II controlled substance and is expected to become commercially available later this year. It will be supplied in child-resistant blister packs of thirty tablets in the following strengths: 8.6 mg. 17.3 mg, or 25.9 mg.
Last month, the FDA also approved Mydayis® (mixed salts of single-entity amphetamine). Mydayis is an extended-release, once daily capsule indicated for the treatment of ADHD in patients 13 years and older. In clinical trials, Mydayis was studied in more than 1,600 adolescents and adults with ADHD. Mydayis was found to significantly improve ADHD symptoms. Improvements in performance were observed within 2 to 4 hours post-dose and continued for a duration of 16 hours post-dose. The most common side effects observed in adults and pediatric patients were insomnia, decreased appetite, and decreased weight. Adult patients also experienced dry mouth, increased heart rate, and anxiety, whereas pediatric patients experienced irritability and nausea. Mydayis is a schedule II controlled substance and will be available as extended-release capsules in the strengths of 12.5 mg, 25 mg, 37.5 mg, and 50 mg. It is expected to become commercially available in the third quarter of 2017.
Orencia® Now Indicated for Psoriatic Arthritis
Orencia® (abatacept), a selective T cell co-stimulation modulator, recently received approval for the treatment of psoriatic arthritis in adults. Orencia is also approved for moderately to severely active rheumatoid arthritis (RA) in adults and moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. Orencia should not be given concurrently with tumor necrosis factor blockers, such as Humira® (adalimumab), due to the potential for an increased risk of serious infections.
The efficacy and safety of Orencia for the treatment of psoriatic arthritis was demonstrated in two clinical trials (PsA-I and PsA-II). In these trials, Orencia reduced disease activity in patients with high disease activity, swollen / tender joints, and a disease duration of more than 7 years. In the PsA-I trial, 170 patients received the intravenous (IV) formulation of either abatacept or placebo on days 1, 15, 29 and then every 28 days. Patients were allowed to continue on background therapy of methotrexate, low-dose corticosteroids, or non-steroidal anti-inflammatory drugs (NSAIDs). In the PsA-II trial, 424 patients were randomized to receive weekly subcutaneous (SQ) injections of abatacept or placebo for 24 weeks. Patients enrolled were allowed to continue methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, low-dose corticosteroids, or NSAIDs. Compared to placebo, a greater proportion of patients receiving the IV or SQ formulation of abatacept achieved the primary endpoint at week 24.
The IV and SC formulations of Orencia are both approved for psoriatic arthritis. For IV administration, Orencia is dosed based on the patient’s body weight and is given at week 0, 2, and 4 followed by maintenance dosing every 4 weeks. For SQ administration, Orencia is administered as a 125 mg injection once weekly. Orencia is currently a specialty medication on standard NPS formularies and carries an average wholesale price (AWP) of $1,148.57 per 125 mg SQ dose.
FDA Safety Update
Risk of Meningococcal Disease with Soliris®
Earlier this month, the Centers for Disease Control and Prevention (CDC) published a Morbidity and Mortality Weekly Report (MMWR) regarding Soliris® (eculizumab) and its risk for invasive meningococcal disease despite previous vaccination. Approved in 2007, Soliris is an intravenously (IV) administered complement inhibitor indicated for the treatment of two rare, life-threatening conditions: paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Soliris carries a Black Box Warning regarding the increased risk for serious meningococcal infections (septicemia and/or meningitis) due to its association with an increased incidence (1,000 to 2,000 fold) of meningococcal disease. Soliris has limited availability, requiring prescriber and voluntary patient enrollment in the Soliris Risk Evaluation & Mitigation Strategy (REMS) program. The Advisory Committee on Immunization Practices (ACIP) recommends patients who are going to take eculizumab receive both the quadrivalent (MenACWY) and serogroup B specific (MenB) meningococcal vaccines. Patients without a history of vaccination should be vaccinated at a minimum of 2 weeks prior to initiation of therapy.
In February 2017, the CDC requested meningococcal disease case records from 2008 to 2016. Records were provided by 47 state health departments and a search of the FDA Adverse Event Reporting System was also performed by the CDC. Sixteen cases of meningococcal disease (median patient age of 30 years) were identified in patients who had received Soliris – all 16 cases were diagnosed as blood stream infections (6 cases had evidence of brain and spinal cord involvement). The majority of cases were caused by nongroupable Neisseria meningitides, and most patients had received 1 or more doses of MenACWY vaccine prior to disease onset. However, MenACWY and MenB vaccines are serogroup specific, and therefore cross-protection against nongroupable strains has yet to be determined.
In an attempt to further decrease the risk of meningococcal disease in patients receiving eculizumab, antimicrobial prophylaxis for the duration of treatment (often lifelong) may be considered. In the United States, studies of invasive meningococcal isolates have shown that penicillin-resistant strains are rare. Long-term prophylaxis with penicillin is generally safe, however the effectiveness of penicillin long-term for meningococcal disease prevention has not been determined. Macrolide antibiotics may be considered in instances of penicillin allergy.
Meningococcal vaccination and antibiotic prophylaxis cannot guarantee prevention of meningococcal disease while using Soliris. Therefore regardless of vaccination and/or antibiotic prophylaxis status, patients and health care providers should be aware of the symptoms of meningococcal disease. Patients should be instructed to seek early care and rapid treatment should they become symptomatic. For additional information, please view the CDC’s MMWR.
FDA Approval and Launch of Second Biosimilar to Remicade®
In April of 2017, the FDA approved Renflexis® (infliximab-abda), a biosimilar to reference product Remicade® (infliximab). Biosimilars are approved under an abbreviated licensure pathway allowing for existing information on the reference product to serve as part of the review for the biosimilar product, thereby reducing development costs. Renflexis is the second biosimilar to Remicade that has received FDA approval. The first biosimilar to Remicade, Inflectra® (infliximab-dyyb) was approved in April of 2016.
Renflexis is a tumor necrosis factor (TNF) blocker and received FDA approval for seven of Remicade’s eight indications, including: moderate to severely active Crohn’s disease in adult and pediatric patients 6 years and older, moderate to severely active ulcerative colitis in adults, moderate to severely active rheumatoid arthritis in combination with methotrexate, active ankylosing spondylitis, active psoriatic arthritis, and chronic, severe plaque psoriasis. Renflexis was not approved for the indication of pediatric ulcerative colitis, as Remicade is protected from competition for this indication due to orphan drug exclusivity status until 2018. Approval for Renflexis was based on analytical, nonclinical and clinical data demonstrating that Renflexis is highly similar to Remicade. Renflexis carries the same black box warning as Remicade regarding the risk for serious infections and lymphoma/other cancers.
Renflexis is commercially available in 100 mg single-dose vials for reconstitution and is administered by intravenous infusion. Dosing is dependent on the indication for use and is weight-based (3 mg/kg, 5 mg/kg, or 10 mg/kg per dose) with maintenance dosing of every 6 to every 8 weeks. A 100 mg vial of Renflexis carries an average wholesale price of $904.07. In comparison, a 100 mg vial of Inflectra carries an AWP of $1,135.54, and the AWP for a 100 mg vial of Remicade is $1,401.38. At the current time, Renflexis is priced at a 35% discount to reference product Remicade, offering a 16% greater discount than the first Remicade biosimilar, Inflectra. NPS is planning to review the new biosimilar for placement on the national formularies.
FDA Advisory Panel Votes in Favor of First CAR-T Cell Therapy
Earlier this month, an advisory panel to the U.S. FDA reviewed the safety and effectiveness of the experimental gene therapy tisagenlecleucel (CTL019) for the treatment of pediatric and young adults aged 3 to 25 years with relapsed/refractory B-cell acute lymphoblastic leukemia. The advisory committee voted unanimously in favor of approval of tisagenlecleucel for the proposed indication. If approved, tisagenlecleucel will be the first gene therapy approved for use in the U.S. The FDA is expected to make a decision regarding approval of the gene therapy by October 3, 2017.
Tisagenlecleucel is a chimeric antigen receptor T cell (CAR-T) therapy, which uses the patients existing T cells to attack cancer cells. Blood is removed from the patient, and T cells are extracted and manipulated to add a receptor that targets a marker found on the leukemia cells. The cells also have a mechanism added to allow them to replicate in the body in order to attack other leukemia cells. These engineered T cells are then infused back into the patient. In general, CAR-T therapy requires close monitoring of the patient due to the potential for very serious, potentially life-threatening side effects. As a result of these safety precautions, if tisagenlecleucel is approved, it will only be available at 30 to 35 highly specialized centers across the U.S. At this time, it is unknown how long these engineered T cells will persist in the body and the long-term safety of gene therapies such as tisagenlecleucel requires further evaluation.
The CAR-T therapy is a one-time treatment and may potentially provide a cure to the patient’s cancer. Therefore, it is expected to be a costly therapy. Additional CAR-T therapies are under development for treating various cancers, including axicabtagene ciloleucel (KTE-C19) which is being developed by Kite Pharma for the treatment of refractory non-Hodgkin’s lymphoma. A decision is expected on Kite Pharma’s CAR-T therapy by November 29th of this year. To view the advisory committee briefing document on tisagenlecleucel in its entirety, please visit the FDA website.
Pfizer Drug Shortage Update
To address the ongoing shortage of sodium bicarbonate injection, the FDA has released a list of additional products that qualify for extended use dates based on stability data provided by Pfizer. The extended use dates are based on lot number. Additional information can be found on the FDA website.
Discontinuation of Seizure Drug and Antibiotic
Earlier this month, GlaxoSmithKline announced the seizure drug, Potiga® (ezogabine), and antibiotic oral suspension, Ceftin® (cefuroxime axetil), would be discontinued.
Potiga is indicated as an adjunctive treatment for partial-onset seizures in patients with inadequate response to alternative treatments. The manufacturer has stated drug removal was not due to safety or efficacy concerns. However in 2013, the labeling for Potiga was updated to include a black box warning regarding the risk for permanent retinal abnormalities, potential vision loss, and skin discoloration. Pharmacies and wholesalers have been instructed to stop distribution and quarantine any of the affected products which include the Potiga 50 mg, 200 mg, 300 mg and 400 mg tablets.
Ceftin is a cephalosporin antibiotic indicated for the treatment of the following infections: pharyngitis/tonsillitis, acute bacterial otitis media, acute bacterial maxillary sinusitis, acute bacterial exacerbations of chronic bronchitis, uncomplicated skin and skin structure infections, uncomplicated urinary tract infections, uncomplicated gonorrhea, Lyme disease, and impetigo. The manufacturer has stated product discontinuation is not related to any safety, quality, or efficacy issues. The 125 mg/mL (100 mL bottle) and 250 mg/5 mL (50 mL and 100 mL bottles) have the following expected final dates of availability: April 1, 2018, January 15, 2018, and February 15, 2018, respectively. Although the Ceftin oral suspension formulations will no longer be commercially available, the 250 mg and 500 mg generic cefuroxime tablets will remain available.
For additional details on these drug discontinuations, please visit the manufacturer’s website.
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