- New Specialty Drug Approvals
- New Drug Launches
- New Indication
- FDA Safety Update
- Pipeline Update
- Over-the-Counter (OTC) Products Update
- Drug Shortages/Discontinuations
New Specialty Drug Approvals
FDA Approves New Hepatitis C Medication: Mavyret®
Hepatitis C is a viral disease that causes inflammation of the liver, which can lead to decreased liver function and in some cases liver failure. According to the Centers for Disease Control and Prevention (CDC), an estimated 2.7 to 3.9 million people in the United States have chronic hepatitis C virus (HCV). There are six known HCV genotypes; genotype 1 is the most common affecting approximately 75% of Americans with HCV.
AbbVie’s new drug Mavyret® (glecaprevir/pibrentasvir) was approved on August 3, 2017 for the treatment of adults with chronic HCV genotypes 1-6 without liver disease (cirrhosis) or with mild cirrhosis. Mavyret can be used in patients with moderate to severe kidney disease as well as in patients on dialysis. It is also indicated for adults with genotype 1 HCV who have previously been treated with a regimen containing either an NS5A inhibitor or an NS3/4A protease inhibitor, but not both. Unlike other drugs approved for HCV that have a treatment length of 12 weeks, Mavyret is the first 8-week treatment option for patients with genotypes 1-6 who do not have cirrhosis. Mavyret also is priced competitively as it carries an average wholesale price (AWP) of $15,840.00 per month, compared to its competitors Harvoni® ($37,800 per month), Epclusa® ($29,904 per month), and Zepatier® ($21,840 per month).
Mavyret was proven to be safe and effective based on clinical trials enrolling approximately 2,300 adults with chronic HCV, genotypes 1-6. The most common side effects observed in the studies included headache, fatigue, and nausea. As with other direct-acting antiviral agents indicated for HCV, there is a potential for Mavyret to cause reactivation of hepatitis B virus (HBV) in patients with both HBV and HCV. Therefore, Mavyret carries a black box warning regarding HBV reactivation in these patients, as some patients with HBV reactivation have experienced liver failure and death. Clinicians are advised to screen all patients for evidence of current or prior infection with HBV before initiating treatment with a direct-acting antiviral agent, such as glecaprevir/pibrentasvir.
Mavyret is supplied as an oral tablet with recommended dosing of three tablets taken once daily with food. The duration of therapy is dependent on the patient’s genotype, liver status (no cirrhosis vs. compensated cirrhosis), and previous HCV treatment regimens. NPS is planning to review Mavyret for placement on the national formularies. For additional information on the approval of Mavyret, please view the FDA’s News Release.
New Drug Launches
New Medication for Psoriasis Available: Tremfya®
In July 2017, the U.S. Food and Drug Administration (FDA) approved Tremfya® (guselkumab) for the treatment of moderate to severe plaque psoriasis in patients who are candidates for systemic therapy or phototherapy. Plaque psoriasis is a condition that causes raised, inflamed red skin covered with dry itchy patches and scales which could appear anywhere on the skin. Tremfya selectively blocks interleukin (IL)-23, which plays an important role in plaque psoriasis in regards to the inflammatory immune response.
FDA approval of guselkumab was based on the VOYAGE 1, VOYAGE 2, and NAVIGATE Phase III clinical trials which evaluated over 2,000 patients. At week 16 in both the VOYAGE 1 and VOYAGE 2 trials, 70% or more of patients who received guselkumab achieved a 90% reduction in the psoriasis severity score (PASI 90) and more than 80% of patients were determined to have clear or almost clear skin. In addition, 90% of patients who achieved PASI 90 at week 28 with guselkumab maintained the improvements through week 48. When evaluated against Humira® (adalimumab), superior efficacy in skin clearance (PASI 90) was observed with guselkumab at weeks 16, 24, and 48. The NAVIGATE study also showed significant improvements with guselkumab compared with the competitor agent Stelara® (ustekinumab). The results at week 28 showed 31% of Tremfya-treated patients achieved clear or almost clear skin compared to 14% of patients taking ustekinumab. Some of the most common adverse effects of guselkumab include upper respiratory infections, headache, injection site reactions, and joint pain.
Tremfya is supplied as a single-dose prefilled syringe of 100 mg/1 mL with an average wholesale price (AWP) for 1 mL (100 mg) of $11,620.80. A 100 mg dose is given subcutaneously at week 0, week 4, and then every 8 weeks thereafter. In contrast, the biologic Humira carries an AWP of $2,664.74 per each 40 mg dose with maintenance dosing of every other week. NPS is planning to review Tremfya for placement on the national formularies. For additional information on the new plaque psoriasis medication, please view the manufacturer’s press release.
Lynparza® Now Indicated for Maintenance Treatment
On August 17th, the FDA expanded the indication for Lynparza® (olaparib) to include maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. This supplemental indication is in addition to Lynparza’s indication for the treatment of adults with deleterious germline BRCA-mutated advanced ovarian cancer, who have been treated with three or more prior lines of chemotherapy. With the addition of this new indication, a tablet formulation of Lynparza is now available along with the pre-existing capsule. The manufacturer is in the process of phasing out the olaparib capsules; the capsules will only be available through the Lynparza Specialty Pharmacy Network.
Two clinical trials collectively enrolling 560 patients, SOLO-2 and Study 19, were conducted to assess the safety and efficacy of olaparib for maintenance therapy. Both studies concluded that olaparib significantly improved progression-free survival (PFS) in patients randomized to olaparib compared to placebo. For SOLO-2, the estimated median PFS was 19.1 months and 5.5 months in the olaparib arm and placebo arm, respectively. In Study 19, the estimated median PFS was 8.4 months for olaparib-treated patients and 4.8 months for patients who received placebo. Some of the most common adverse effects (≥ 20%) observed in clinical trials were anemia, nausea, fatigue, vomiting, diarrhea, muscle pain, headache, upset stomach, constipation, and painful sores inside the mouth (oral mucositis).
Lynparza is available as 100 mg and 150 mg tablets, and 50 mg capsules. Lynparza tablets and capsules are not interchangeable. For both maintenance therapy and later line treatment the recommended dose is 300 mg (two 150 mg tablets) taken by mouth twice daily with or without food. The average wholesale price (AWP) for one Lynparza 150 mg tablet is $134.82.
FDA Safety Update
International Laboratories, LLC has voluntarily recalled one lot of pravastatin 40 mg tablets (NDC 54458-0925-16) due to a pharmacist report that a 30-count bottle was mislabeled and contained bupropion hydrochloride XL 300 mg tablets instead. Pravastatin is used to lower cholesterol levels along with diet and exercise, while bupropion is an antidepressant used to treat major depressive disorder and seasonal affective disorder. The affected product is supplied in a bottle of 30 tablets with the lot number 115698A. NPS has notified potentially affected members and their healthcare providers of the recall by mail.
PharmaTech Liquids Recall
On August 3, 2017, Rugby Laboratories issued a voluntary nationwide recall of all lots of Diocto® Liquid (docusate sodium) and Diocto® Syrup (docusate sodium) manufactured by PharmaTech, LLC due to the potential for contamination by the bacteria Burkholderia cepacia. These products are used as stool softeners and were distributed across the country to wholesalers, hospitals, and pharmacies. The FDA received multiple reports regarding infections caused by B. cepacia in patients who had used these products. All lots with NDC 0536-0590-85 or NDC 0536-1001-85 were recalled. NPS notified members with affected NDCs and their healthcare prescriber of the Diocto product recall by mail.
The following week, the FDA issued a Safety Alert instructing healthcare providers and patients not to use any liquid product manufactured by PharmaTech due to potential contamination with B. cepacia. Patients, pharmacies, and healthcare facilities with any liquid PharmaTech products were recommended to stop use immediately. Product contaminated with B. cepacia can lead to serious or life-threatening infections in patients who have weakened immune systems or chronic lung conditions such as cystic fibrosis.
On August 10, 2017, additional companies, Major Pharmaceuticals and Leader Brand, jointly issued a voluntary recall of all liquid products manufactured by PharmaTech LLC. The recall included all lots within expiry. For a complete listing of affected products and their NDCs, please view the FDA Company Announcement. NPS has notified members with potentially affected products and their healthcare prescribers of the expanded recall by mail, and instructed patients to stop using the product immediately.
To view additional details regarding the recalled liquid products due to potential contamination with B. cepacia, please view the FDA’s Drug Safety Update.
Advisory Committee Votes Against Approval of New Rheumatoid Arthritis Drug
Plivensia® (sirukumab) is a human monoclonal antibody that was developed for the treatment of moderate to severe rheumatoid arthritis (RA) in adults with inadequate response or who are unable to tolerate one or more disease modifying anti-rheumatic drugs (DMARDs). Although two Phase 3 clinical trials showed sirukumab improved signs and symptoms, inhibited progression of structural damage, and improved patient-reported outcome measures (i.e. fatigue, pain, quality of life), an advisory committee to the FDA voted the benefits do not outweigh the risks. Serious adverse events such as pneumonia, skin and bone infections, cancer, cardiovascular effects, and death were seen in clinical studies. Other commonly reported adverse events include redness, pain, or swelling at the site of injection.
Kevzara® (sarilumab) and Actemra® (tocilizumab) were approved in May 2017 and January 2010, respectively, for use in the same population of RA patients. Similar to these agents, sirukumab also targets the interleukin-6 (IL-6) pathway, however it acts directly on the IL-6 cytokines rather than the IL-6 receptor. Agents that target the IL-6 pathway have been associated with a partial or complete suppression of the immune response and related adverse events. In the studies, thirty-five reported deaths occurred, and thirty-four of these deaths occurred in patients taking sirukumab. Due to these risks, the FDA Arthritis Advisory Committee voted overwhelmingly not to recommend sirukumab as treatment for RA despite demonstrating adequate efficacy. The FDA is not obligated to accept the recommendations from the advisory committee but generally takes their advice into consideration.
Over-the-Counter (OTC) Products Update
Store-branded OTC Nexium® Available Soon
Perrigo Company has received final approval from the FDA to package and sell a store-brand equivalent of over-the-counter Nexium® 24 HR (esomeprazole magnesium). The company has reached a patent-lawsuit settlement with AstraZeneca who is the originator of Nexium. This will be the first over-the-counter generic version of esomeprazole magnesium and is expected to be available in late September 2017. Nexium® 24 HR capsules are used to treat frequent heartburn occurring 2 or more days a week.
Atenolol Drug Shortages
At the end of July, the FDA reported a shortage of all strengths of generic atenolol tablets manufactured by Mylan Pharmaceuticals, Sandoz, and Teva Pharmaceuticals. These manufacturers listed the atenolol shortage as being caused by a shortage of the active ingredient. The manufacturers have not yet announced any anticipated release dates for additional product to become available. However, the atenolol tablets made by Zydus Pharmaceuticals USA Inc. are currently available, and the company has increased their capacity to meet additional demands. For the most up-to-date information on drug shortages, please visit the ASHP Drug Shortage Resource Center or the FDA Drug Shortage Website.
Discontinuation of Generic Pfizer Products
At the end of July, Pfizer Pharmaceuticals announced the discontinuation of their generic spironolactone tablets, sertraline tablets, and azithromycin film-coated tablets. The generic spironolactone tablet and sertraline tablet were both available in the strengths of 25 mg, 50 mg, and 100 mg, and the generic azithromycin film-coated tablet was available in the strengths of 250 mg, 500 mg and 600 mg. Other generic versions of these products are expected to remain commercially available.
Discontinuation of Qvar® (beclomethasone dipropionate HFA) Inhalation Aerosol
Earlier this month, Teva Pharmaceuticals announced the discontinuation of Qvar® (beclomethasone diproprionate HFA) metered-dose inhaler (MDI). The discontinuation will affect both the 40 mcg and 80 mcg strengths of the product and is due to a business decision. Teva recently received FDA approval for the Qvar RediHaler® which contains the same active ingredient as Qvar, but provides delivery of the orally inhaled steroid via a breath-actuated MDI that does not require hand-breath coordination.
The Qvar MDI formulation will be discontinued upon launch of the new Qvar RediHaler in the first quarter of 2018. Qvar RediHaler is indicated for the maintenance treatment of asthma as prophylactic therapy in patients 4 years of age or older. Qvar MDI is indicated for maintenance therapy of asthma as prophylactic therapy in patients 5 years of age and older. NPS plans to provide ongoing communication regarding the discontinuation of Qvar MDI and launch of the new RediHaler formulation.
- FDA approves Mavyret for hepatitis C. FDA Press Announcements. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm570038.htm. Updated August 3, 2017. Accessed August 28, 2017.
- Sagonowsky E. AbbVie’s new pan-genotypic hepatitis C drug Mavyret deeply underprices the competition. FiercePharma. http://www.fiercepharma.com/pharma/abbvie-s-new-pan-genotypic-hep-c-drug-mavyret-undercuts-competition. Published August 3, 2017. Accessed August 28, 2017.
- Lowes R. FDA OKs 8-week Mayvret for hepatitis C. Medscape Medical News: FDA Approvals. http://www.medscape.com/viewarticle/883778. August 3, 2017. Accessed August 28, 2017.
- Hee Han D. Tremfya approved for moderate to severe plaque psoriasis. EMPR.com. http://www.empr.com/news/tremfya-moderate-to-severe-plaque-psoriasis/article/674942/. Updated July 13, 2017. Accessed August 28, 2017.
- FDA approves Tremfya for moderate to severe plaque psoriasis. P&T Community. https://www.ptcommunity.com/news/20170717/fda-approves-tremfya-moderate-severe-plaque-psoriasis. Updated July 13, 2017. Accessed August 28, 2017.
- Tremfya [package insert]. Horsham, PA: Janssen Biotech Inc; July 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761061s000lbl.pdf. Accessed August 28, 2017.
- FDA approves olaparib tablets for maintenance treatment in ovarian cancer. FDA Approved Drugs. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm572143.htm. Updated August 17, 2017. Accessed August 28, 2017.
- Gold Standard, Inc. Lynparza monograph. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology.com. Accessed: August 28, 2017.
- International Laboratories, LLC issues voluntary nationwide recall of one lot of pravastatin sodium tablets USP, 40 mg packaged in bottles of 30 tablets due to mislabeling NDC #54458-925-16; Lot # 115698A. U.S. Food and Drug Administration: Recalls, Market Withdrawals, & Safety Alerts. https://www.fda.gov/Safety/Recalls/ucm571019.htm. Updated August 9, 2017. Accessed August 25, 2017.
- Diocto Liquid and Diocto Syrup by Rugby Laboratories: Recall – Possible product contamination. FDA MedWatch: Safety Alerts for Human Medical Products. https://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm570014.htm. Updated August 3, 2017. Accessed August 29, 2017.
- Liquid drug products manufactured by PharmaTech and distributed by Rugby Laboratories and possibly other companies: FDA Advisory – Not to Use. U.S. FDA: Safety Alerts for Human Medical Products. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm570674.htm. Updated August 8, 2017. Accessed August 29, 2017.
- Liquid products manufactured by PharmaTech and distributed by Leader Brand, Major Pharmaceuticals, and Rugby Laboratories: Recall – Possible product contamination. U.S. FDA: Safety Alerts for Human Medical Products. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm570997.htm. Updated August 10, 2017. Accessed August 29, 2017.
- Hee Han D. FDA committee votes against RA drug candidate approval. EMPR.com. http://www.empr.com/news/sirukumab-plivensia-rheumatoid-arthritis-advisory-panel/article/679604. Updated August 3, 2017. Accessed August 28, 2017.
- Brown T. Sirukumab not recommended for RA on mortality concerns. Medscape Medical News. http://www.medscape.com/viewarticle/883729. Updated August 2, 2017. Accessed August 28, 2017.
- Store-branded OTC Nexium to launch by end of September. P&T Community. https://www.ptcommunity.com/news/20170821/store-branded-otc-nexium-launch-end-september. Updated August 21, 2017. Accessed August 28, 2017.
- Perrigo announces final FDA approval and settlement for the store brand OTC equivalent of Nexium® 24HR capsules. PRNewswire. http://www.prnewswire.com/news-releases/perrigo-announces-final-fda-approval-and-settlement-for-the-store-brand-otc-equivalent-of-nexium-24hr-capsules-300506984.html. Published August 21, 2017. Accessed August 28, 2017.
- Atenolol tablets. FDA Drug Shortages. https://www.accessdata.fda.gov/scripts/drugshortages/. Updated August 16, 2017. Accessed August 25, 2017.
- Spironolactone tablets. FDA Drug Shortages. https://www.accessdata.fda.gov/scripts/drugshortages/. Updated July 27, 2017. Accessed August 29, 2017.
- Sertraline tablets. FDA Drug Shortages. https://www.accessdata.fda.gov/scripts/drugshortages/. Updated July 27, 2017. Accessed August 29, 2017.
- Azithromycin tablets. FDA Drug Shortages. https://www.accessdata.fda.gov/scripts/drugshortages/. Updated July 27, 2017. Accessed August 29, 2017.
- Beclomethasone dipropionate HFA inhalation Aerosol. FDA Drug Shortages. https://www.accessdata.fda.gov/scripts/drugshortages/. Updated August 16, 2017. Accessed August 29, 2017.
- Teva announces FDA Approval of QVAR RediHaler inhalation aerosol. Medical Device News Magazine. https://infomeddnews.com/2017/08/teva-announces-fda-approval-qvar-redihaler-inhalation-aerosol/. Updated August 7, 2017. Accessed August 29, 2017.
- QVAR [prescribing information]. Frazer, PA: Teva Respiratory, LLC; May 2017. Available at: http://www.qvar.com/library/docs/prescribing-information.pdf. Accessed August 29, 2017.