New Specialty Drug Approvals
FDA Approves New Biologic for Rheumatoid Arthritis
In May of 2017, the U.S. Food & Drug Administration (FDA) approved a new medication, Kevzara® (sarilumab), for the treatment of moderately to severely active rheumatoid arthritis (RA). Kevzara is indicated specifically for adults who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drug (DMARDs), such as methotrexate (MTX). Kevzara is an interleukin-6 receptor (IL-6R) inhibitor, which helps to decrease the inflammatory processes associated with RA. Sarilumab can be used alone or in combination with MTX or other non-biologic DMARDs.
The efficacy and safety of sarilumab was demonstrated in two phase III clinical trials evaluating approximately 2,900 adults who had an inadequate response to prior treatments. When combined with MTX, sarilumab demonstrated statistically and clinically significant improvements in patients with moderately to severely active RA at week 24 compared to patients who received placebo + MTX. Studies have also shown when Kevzara is used in combination with either MTX or DMARDs, it reduces the signs and symptoms of RA and improves physical function compared to patients treated with placebo. The most common adverse effects observed with Kevzara are low white blood cell (WBC) counts, increased liver enzymes, injection site redness, upper respiratory infection, and urinary tract infection. Kevzara carries a boxed warning for the increased risk of developing serious infections, and use should be avoided in patients with an active infection.
Kevzara is supplied as prefilled syringes in two count packs, either as a 150 mg/1.14 mL single-dose syringe or in a 200 mg/1.14 mL dosage strength. The recommended dosage is 200 mg of sarilumab once every two weeks as a subcutaneous injection. Some patients may require dose reduction to 150 mg once every two weeks due to low WBC counts, low platelet levels, or increased liver enzymes. The average wholesale price (AWP) for one syringe of sarilumab is $1,800.00. For more information, please view manufacturer’s press release.
FDA Approves New Drug for Osteoporosis in Postmenopausal Women
On April 28, 2017, the FDA approved a new medication, Tymlos® (abaloparatide), for the treatment of postmenopausal women with osteoporosis who are at a high risk for fracture. Patients with a high fracture risk include those with a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis treatment. Tymlos is the first new bone building drug approved for postmenopausal women with osteoporosis in nearly 15 years.
The efficacy and safety of abaloparatide were demonstrated in a randomized, double-blind, placebo-controlled clinical trial evaluating more than 2,000 women. Abaloparatide demonstrated an increase in bone mineral density and reduced the risk of new vertebral and nonvertebral fractures compared with placebo at the end of month 18. The most common adverse effects observed with Tymlos were elevation of calcium in the urine and dizziness. Tymlos carries a boxed warning regarding an increase in the incidence of bone cancer, based on animal data. Also, it is not recommended to use abaloparatide for more than 2 years during a patient’s lifetime. In addition, abaloparatide carries warnings/precautions for low blood pressure when standing, high calcium levels in the blood, high calcium levels in the urine, and formation of kidney stones.
Tymlos is supplied as a pre-assembled, single patient-use disposable pen. Each disposable pen contains 3,120 mcg of abaloparatide in 1.56 mL (2,000 mcg/mL), which provides a 30-day supply of abaloparatide. The recommended dose is 80 mcg administered subcutaneously (under the skin) once daily into the right lower region of the stomach. The average wholesale price (AWP) for a 30-day supply is $1,950.
Tymlos is expected to compete directly with the other agent in its class indicated for the treatment of postmenopausal women with osteoporosis who are at a high risk of fracture, Forteo® (teriparatide). Forteo also carries additional indications for 1) increasing bone mass in men with osteoporosis who are at a high risk for fracture and 2) the treatment of patients with steroid-induced osteoporosis who are at a high risk of fracture. Forteo is also given once-daily and also carries a boxed warning for bone cancer. For additional information, please view the manufacturer’s press release.
Biologic Drug Actemra® Now Indicated for Giant Cell Arteritis
Last month, the FDA expanded the approved use of subcutaneous Actemra® (tocilizumab) to treat adults with giant cell arteritis. Actemra is an interleukin-6 (IL-6) receptor antagonist available in both a subcutaneous and intravenous formulation. The subcutaneous formulation is approved to treat adult patients with moderate to severe rheumatoid arthritis (RA) who have had an inadequate response to one or more disease-modifying antirheumatic drug (DMARDs). In addition to the RA indication, the intravenous (IV) formulation is also approved for systemic juvenile idiopathic arthritis (SJIA) and polyarticular juvenile idiopathic arthritis (PJIA).
Actemra is the first and only biologic therapy FDA-approved for treating giant cell arteritis. Actemra was granted Breakthrough Therapy designation and Priority Review for this use. Giant cell arteritis, also known as temporal arteritis, is a type of vasculitis, in which the blood vessels in the head are inflamed. The condition is generally treated with high-dose corticosteroids with tapering over time.
The approval was based on the GiACTA study, a phase III, double-blind, placebo controlled trial that evaluated 251 patients with giant cell arteritis. A higher percentage of patients treated with Actemra + standardized prednisone regimen, achieved a sustained remission from week 12 through 52 compared to patients treated with placebo + standardized prednisone regimen. Sustained remission was defined as the absence of symptoms, normalization of inflammatory markers, and tapering of prednisone. In addition, patients that received Actemra were able to take lower cumulative doses of prednisone compared to patients who received placebo. Actemra carries a boxed warning for serious infections, and treatment with Actemra should be withheld if an infection occurs. Patients receiving Actemra should also undergo laboratory monitoring for white blood cell counts, platelet levels, lipid levels, and liver enzymes in case dose modifications are required. Actemra is administered as a subcutaneous injection once every week and carries an average wholesale price (AWP) of $154.00 per day.
Expanded Indication for Lung Cancer Drug Zykadia®
Last month, the FDA expanded the indication of Zykadia® (ceritinib) for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) positive, as detected by an FDA-approved test. The kinase inhibitor was granted Priority Review for this use in the first-line setting. Zykadia was already approved for the treatment of patients with ALK-positive metastatic NSCLC who had progression on or were intolerant to Xalkori® (crizotinib). Zykadia has also received Breakthrough Therapy designation as a first-line treatment for patients with ALK-positive metastatic NSCLC with metastases to the brain.
The expanded approval was based on a data from ASCEND-4 phase III, randomized, open-label, multicenter trial which demonstrated Zykadia-treated patients had significantly improved progression-free survival (16.6 months) compared to patients treated with standard first-line pemetrexed-platinum chemotherapy (8.1 months). Zykadia is expected to compete directly with the other first-line therapy indicated for ALK-positive metastatic NSCLC, Xalkori. For additional information, please view the manufacturer’s press release.
FDA Safety Update
FDA Requests Removal of Opioid Pain Medication from the Market
On June 8th, the FDA requested the manufacturer of Opana ER® (oxymorphone hydrochloride) voluntarily remove the extended-release opioid pain reliever from the U.S. market. The FDA has concluded the benefits of the drug no longer outweigh its risk and is taking steps to stop the sale of the medication in the U.S. due to concerns regarding abuse. If the manufacturer of Opana ER, Endo Pharmaceuticals, does not remove Opana ER from market voluntarily, the FDA plans to withdraw approval of the product. Endo Pharmaceuticals has been reported to be communicating with the FDA regarding the request.
Opana ER is an extended-release formulation of oxymorphone and is a schedule II controlled substance. It was approved in 2006 for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are not adequate. In 2012, the product was reformulated to prevent physical and chemical manipulation used to abuse the medication. Although the reformulated product met FDA approval standards, it did not demonstrate an adequate reduction in abuse potential and therefore did not receive labeling regarding abuse-deterrent properties.
Recent post-marketing data has demonstrated the reformulated version of the Opana ER has resulted in a shift from nasal abuse of the drug to abuse via injection, and abuse of the drug via injection has been associated with outbreaks of HIV, hepatitis C and a serious blood condition. In March 2017, an FDA advisory committee recommended 18 to 8 that the benefits of the reformulated product no longer outweigh its risks. Due to these serious concerns regarding the abuse potential of Opana ER, the FDA has requested the manufacturer voluntarily stop commercialization of the product.
The FDA is communicating the detrimental effects associated with abuse of Opana ER and requesting the manufacturer remove the product from market in an effort to protect the public from further harm. The FDA has stated they will continue to evaluate the risks versus benefits of approved opioid products with additional action taken as necessary.
NPS plans to provide ongoing communication regarding the commercial availability and approval status of Opana ER. For additional details regarding the FDA request, please view the FDA News Release. For details regarding Endo Pharmaceutical’s response, please view the company’s press release. For additional information on the product, please view the FDA’s summary.
Supreme Court Rules Regarding Time Frame for Launch of Biosimilars
Earlier this month, the U.S. Supreme Court issued a unanimous decision regarding the commercial launch of biosimilars following their approval by the FDA. The Court voted 9-0 overturning a lower court’s decision that had blocked Sandoz from marketing Zarxio® (filgrastim-sndz), its biosimilar to Amgen’s Neupogen® (filgrastim), until 6 months after the U.S. FDA approval. The disagreement between the two manufacturers was regarding the 180-day notice required to be given to the reference product manufacturer (Amgen) by the biosimilar manufacturer (Sandoz) prior to commercialization of the biosimilar product. In July 2015, the U.S. Court of Appeals for the Federal Circuit in Washington determined the 180-day notice had to be given after FDA approval, resulting in a 6-month extension of exclusivity for the reference product manufacturer.
The Supreme Court’s recent ruling allows biosimilar manufacturers to notify reference product makers of their intent to market the biosimilar prior to FDA-approval, which will allow biosimilars to be launched soon after FDA-approval is granted. Earlier availability of biosimilars is anticipated to increase access and reduce costs, as biosimilars are generally priced at a discount to the originator reference product. Although the Supreme Court decision overturns the appeals court ruling, the Supreme Court has stated state laws may be able to be used to delay the biosimilar launch until 6-months after FDA approval. NPS plans to provide ongoing communication regarding the FDA-approval and commercial launch of biosimilar products.
Update on Draft Guidance for Interchangeable Biosimilars
In January 2017, the FDA released the much-anticipated draft guidance on biosimilar interchangeability which designates the criteria the FDA will use to designate biosimilar products as “interchangeable biosimilars.” Biosimilars which have met this additional criteria for interchangeability will be able to be substituted for the reference product (original product) at the pharmacy without intervention of the prescribing healthcare provider.
Last week, an FDA representative stated comments on the draft guidance on interchangeable biosimilars were currently undergoing review and revised draft guidance or final guidance on the requirements for interchangeability will be released within the next two years. It was also stated the FDA expects interchangeable biosimilars to become commercially available within this same time frame or sooner.
For additional information on biosimilars, please visit the FDA’s website. For additional details on the expected timeline for interchangeable biosimilars, please visit the Regulatory Affairs and Professionals Society website.
Generic Version of ADHD Drug Strattera® Now Commercially Available
In May 2017, the U.S. FDA approved the first generic versions of Strattera® (atomoxetine) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adult and pediatric patients 6 years of age and older. Both the brand and generic versions of the non-stimulant ADHD drug are available as oral capsules in the strengths of 10 mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg or 100 mg. Capsules can be taken with or without food, and therapy with atomoxetine can be discontinued without the need for tapering.
For children and adolescents weighing over 70 kg and adult patients, the initial total daily dose of atomoxetine is 40 mg. After a minimum of 3 days this dose can be increased to a targeted total daily dose of 80 mg given as a single daily dose in the morning or in two divided doses (one in the morning and one in late afternoon/early evening). For patients who do not achieve adequate response after 2 to 4 weeks, the dose may be increased further to a maximum total daily dose of 100 mg. Dose adjustments are required for patients with hepatic impairment, patients who are poor CYP2D6 metabolizers, and patients taking strong CYP2D6 inhibitors.
For children and adolescents with a body weight of 70 kg or less, the initial total daily dose should be based on the patient’s body weight and given at 0.5 mg/kg. This dose can be increased to 1.2 mg/kg after a minimum of 3 days. The maximum dose for these patients is 1.4 mg/kg or 100 mg, whichever is lower. Both the brand and generic products carry a boxed warning for suicidal ideation in children and adolescents, and as a result, patients should be monitored for changes in behavior, worsening of symptoms, and suicidal thoughts/behaviors with initiation of therapy or changes in therapy. Other warnings/precautions include the potential for serious liver injury and serious cardiovascular events.
Strattera has an average wholesale price (AWP) of $15.82 to $18.54 per each oral capsule. Currently there are four manufacturers of the generic product (Teva Pharmaceuticals, Rising Pharmaceuticals, Prasco Laboratories, Glenmark Pharmaceuticals), and the generics carry an AWP of between $14.22 and $16.69 per capsule. NPS is planning to review the generic atomoxetine capsules for placement on the national formularies. For additional information, please view the FDA’s press release.
Hospira Drug Shortages
In mid-June 2017, the U.S. FDA announced they were aware of the ongoing shortages affecting a number of injectable drugs made by Hospira, a Pfizer company. Products affected by the shortage include: sodium bicarbonate injection, dextrose 50% injection, epinephrine injection, calcium chloride injection, and atropine sulfate injection. The shortage is reportedly due to manufacturing, distribution, and third party delays.
The FDA has stated they are working with Hospira to address the shortages and is in the process of identifying alternative sources for these drugs as well as extending beyond use dates when stability data is available. Certain emergency syringe products have been given extended use dates based on lot number. For a full listing of these products, the lot number, and extended use dates, please visit: Extended Use Dates Provided by Pfizer to Assist with Emergency Syringe Shortages.
There has also been a voluntary recall of certain Pfizer products due to the potential for lack of sterility assurance. Certain formulations with specific lot numbers of the following products have been recalled: 8.4% sodium bicarbonate injection, Neut® (sodium bicarbonate 4% additive solution), potassium phosphate injection, and Quelicin® (succinylcholine chloride injection). For a complete listing of recalled Pfizer products due to sterility concerns, please view the company announcement.
Malaria Drug Discontinued
Earlier this month, the FDA announced West-Ward Pharmaceuticals had made a business decision to discontinue the manufacturing of mefloquine HCl 250 mg tablets. Mefloquine is indicated for the treatment of mild to moderate acute malaria caused by mefloquine-susceptible strains and for the prevention of certain strains of malaria. Mefloquine HCl 250 mg tablet manufactured by Teva Pharmaceuticals will continue to be commercially available.
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- FDA approves Radius Health’s TYMLOS™ (abaloparatide), a bone building agent for the treatment of postmenopausal women with osteoporosis at high risk for fracture. Radius News Releases. http://investors.radiuspharm.com/releasedetail.cfm?releaseid=1023557. Updated April 28, 2017. Accessed June 20, 2017.
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- Novartis receives FDA approval for expanded use of Zykadia in first-line ALK-positive metastatic NSCLC. Novartis News Releases. https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-expanded-use-zykadiar-first-line-alk-positive. Updated May 26, 2017. Accessed June 28, 2017.
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- Sagonowsky E. In landmark Amgen v. Sandoz ruling, biosim makers can give notice before FDA nod. FiercePharma. http://www.fiercepharma.com/pharma/biosim-developers-can-provide-marketing-notice-before-approval-scotus. Updated June 12, 2017. Accessed June 28, 2017.
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