New Drug Approvals
New Biologic Approved for Plaque Psoriasis
The U.S. Food and Drug Administration (FDA) recently approved a new monoclonal antibody, Siliq® (brodalumab), for the treatment of adults with moderate-to-severe plaque psoriasis. It is indicated specifically for patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. It is given by subcutaneous injection and is expected to be available later this year as a single-dose prefilled syringe with a list price of $3,500 per month.
Plaque psoriasis is the most common form of the autoimmune disease psoriasis and is characterized by skin redness accompanied by flaky, silver-white scales. Siliq binds to inflammatory cytokine interleukin-17’s receptor, inhibiting the downstream inflammatory process involved in the development of psoriasis. The safety and efficacy of Siliq was established in three randomized, placebo-controlled trials evaluating more than 4,000 adult patients with moderate-to-severe plaque psoriasis. Compared to patients receiving placebo, a greater proportion of patients treated with Siliq exhibited clear or almost clear skin. The most common side effects experienced with Siliq included joint pain, headache, fatigue, diarrhea, throat pain, nausea, muscle pain, injection site reactions, influenza, low white blood cell levels, and ring worm infections. Siliq is contraindicated in patients with Crohn’s disease, and similar to other biologics carries warnings and precautions for infections.
Siliq is expected to compete directly with two other biologics with similar mechanisms of action also indicated for moderate-to-severe plaque psoriasis: Cosentyx® (secukinumab) and Taltz® (ixekizumab). Neither of these products carries a black box warninq (BBW), however Siliq does have a BBW for suicidal ideation and behavior. As a result, it is only available through a restricted Risk Evaluation and Mitigation Strategy (REMS) program. The program requires prescribers and pharmacies to be certified in order to prescribe or dispense Siliq. In addition, patients in the program are required to be counseled about the risks of the medication, be made aware of when to seek medical attention for changes in mood, and sign a Patient-Prescriber Agreement Form.
Upon the commercial launch of Siliq, NPS plans to review the product for placement on the national formularies. For additional information, please view the FDA’s press release.
First Medication Approved for Treatment of Tardive Dyskinesia
The FDA has recently approved the first medication for the treatment of adults with tardive dyskinesia: Ingrezza® (valbenazine). Tardive dyskinesia is a neurological disorder characterized by repetitive uncontrollable movements of the face, trunk, tongue, and extremities which may affect the patient’s ability to walk, speak, and breathe. Patients exposed long-term to certain drugs such as antipsychotics, which block the dopamine receptor, may develop tardive dyskinesia. It is not known why some individuals taking these medications develop the movement disorder. Tardive dyskinesia is currently estimated to affect approximately 500,000 people in the United States.
Ingrezza received Breakthrough Therapy designation and was granted Priority Review by the FDA. Prior to its approval, patients with tardive dyskinesia were managed by changes in dose or discontinuation of the offending antipsychotic. However, changes in therapy can affect the patient’s psychiatric stability. Ingrezza works by inhibiting vesicular monoamine transporter 2 (VMAT2) and has demonstrated a reduction in involuntary movements without affecting patients’ psychiatric stability. Ingrezza is also being studied in adults and adolescents with Tourette syndrome.
The efficacy and safety of Ingrezza was established in a randomized, placebo-controlled trial evaluating more than 230 patients with moderate-to-severe tardive dyskinesia. Patients enrolled had schizophrenia, schizoaffective disorder, or a mood disorder. After 6 weeks of therapy, patients who received Ingrezza demonstrated improvement in the severity of tardive dyskinesia symptoms compared to patients who received placebo. The most common side effect observed with Ingrezza was sleepiness. As a result, patients should not operate a motor vehicle or hazardous machinery until they know how Ingrezza affects them. The product also carries a warning/precaution for QT prolongation and therefore should be avoided in patients with congenital QT syndrome or with arrhythmias associated with a prolonged QT interval.
Ingrezza will be supplied as a 40 mg capsule with initial dosing of 40 mg once daily and maintenance dosing of 80 mg once daily. The wholesale acquisition cost (WAC) for a 30-count bottle is $5,275. Although Ingrezza is currently the only FDA-approved medication for tardive dyskinesia, the FDA is expected to make a decision on the use of another VMAT2 inhibitor, Austedo® (deutetrabenazine), for tardive dyskinesia by late August 2017. For additional information on Ingrezza, view the FDA’s press release.
New Drug Launches
Much-Anticipated Multiple Sclerosis Drug Commercially Available
Last month, the FDA approved a new biologic, Ocrevus® (ocrelizumab), for the treatment of adults with relapsing multiple sclerosis (RMS) or primary progressive multiple sclerosis. Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that impairs communication between the brain and other parts of the body. The majority of patients with MS experience episodes of worsening symptoms (relapse) followed by periods of recovery. As MS progresses, functional decline and disability can occur. Ocrevus is the first agent FDA-approved for primary progressive multiple sclerosis (PPMS).
The Biologics License Application (BLA) reviewed by the FDA included data from three phase III studies: OPERA I, OPERA II, and ORATORIO. In OPERA I and II, ocrelizumab demonstrated superior efficacy to Rebif® (interferon beta-1a) in reducing the annualized relapse rate and disability progression in patients with RMS. In ORATORIO, ocrelizumab demonstrated significant reductions in disability progression compared to placebo in PPMS patients. The most common side effects observed with ocrelizumab were infusion-related reactions and infections. Ocrelizumab is administered by intravenous infusion as a 600 mg dose every 6 months and carries an average wholesale price (AWP) of $39,000 per 600 mg dose. NPS is planning to review ocrelizumab for placement on the national formularies.
Harvoni® and Sovaldi® Now Indicated in Pediatric Patients
The FDA recently expanded the indications of two hepatitis C medications, Sovaldi® (sofosbuvir) and Harvoni® (ledipasvir/sofosbuvir), for use in children ages 12 to 17 years for the treatment of hepatitis C virus (HCV). Previously, these products were approved only for treating adults with HCV. These agents are the first direct-acting antiviral (DAA) agents indicated for treating pediatric patients and are approved for use in patients 12 years and older or weighing at least 35 kg. Sovaldi is indicated for pediatric patients with genotype 2 or 3 chronic HCV infection without cirrhosis or with compensated cirrhosis and is to be used in combination with ribavirin. Harvoni is indicated for pediatric patients with genotype 1, 4, 5 or 6 chronic HCV infection without cirrhosis or with compensated cirrhosis.
The expanded approval was in part based on data from studies conducted in patients 12 years of age or older which demonstrated undetectable hepatitis C virus (sustained viral response) 12 weeks after the conclusion of antiviral treatment with either Harvoni or Sovaldi + ribavirin. The most common side effects observed in these patients were fatigue and headache. Both medications carry a black box warning (BBW) regarding the risk for hepatitis B virus (HBV) reactivation in patients treated with DAA who are infected with both HCV and HBV. As a result, it is recommended all patients be tested for HBV infection prior to initiating therapy; patients with HCV/HBV co-infection should be monitored for HBV reactivation and managed as clinically indicated.
HCV is a viral disease causing liver inflammation which can lead to impaired liver function or liver failure. Children born to HCV-positive mothers are at risk for acquiring the infection. Currently, there are an estimated 23,000 to 46,000 children in the U.S. living with HCV. For additional information on the expanded indications for Sovaldi and Harvoni, please view the FDA’s press release.
FDA Safety Update
EpiPen® Recall Expanded to the U.S.
On March 31st, the U.S. FDA announced a voluntary recall by Meridian Medical Technologies of Mylan’s EpiPen® (epinephrine injection, USP) and EpiPen Jr.® (epinephrine injection, USP) Auto-Injector devices. Previously, the manufacturer had recalled 80,000 EpiPens outside of the U.S. due to a defective part. Although the incidence of the defect is rare and testing has not identified any units with a defect, the recall was expanded out of an abundance of caution and includes 13 lots of EpiPen and EpiPen Jr. auto-injectors distributed in the U.S. between December 17, 2015 and July 1, 2016.
The recall was issued following two reports of the device failing to deliver a dose of the life-saving medication. The two patients who experienced the device malfunctions were successfully treated with a backup EpiPen. However, the faulty part may result in increased force required to activate the needle or the inability to activate the needle entirely. Failure of the device to work could be detrimental to a patient in the event of a life-threatening allergic reaction. Patients are instructed to seek emergency medical help immediately after using their EpiPen, particularly if the device does not activate.
Mylan is planning to replace the recalled devices at no cost, and has instructed patients, customers and distributors to visit www.Mylan.com/EpiPenRecall or call Stericycle at 877-650-3494 for information on product return and replacement instructions. In addition, patients have been instructed to continue to carry and use their current EpiPen until a replacement device is received. Although the number of reported failures is small, the following NDCs with the affected lot numbers and expiration dates are being recalled:
|EpiPen Jr. Auto-Injector 0.15 mg – NDC 49502-0501-02|
|Lot #: 5GN767 and 5GN773||Exp. Date April 2017|
|Lot #: 6GN215||Exp. Date Sept. 2017|
|EpiPen Auto-Injector 0.3 mg – NDC 49502-0500-02|
|Lot #: 5GM631||Exp. Date April 2017|
|Lot #: 5GM640||Exp. Date May 2017|
|Lot #: 6GM082, 6GM072, 6GM081||Exp. Date Sept. 2017|
|Lot #: 6GM088, 6GM199, 6GM091, 6GM198, 6GM087||Exp. Date Oct. 2017|
Patients who have EpiPens from lots not included in this recall, do not need to replace their EpiPen prior to its expiration date. For additional information, please view the FDA News Release or the manufacturer’s press release. For additional questions regarding the recall, the manufacturer can be contacted at 800-796-9526 or email@example.com. NPS has notified members and their healthcare providers via mail of the EpiPen recall.
Copycat of Blockbuster Asthma Drug Launched
Last week, Teva Pharmaceutical Industries launched their copycat, AirDuo RespiClick® (fluticasone proprionate / salmeterol), of blockbuster asthma drug Advair® (fluticasone propionate / salmeterol). Although AirDuo contains the same active ingredients as Advair®, it is not directly substitutable with Advair and only received FDA-approval for the treatment of asthma in patients 12 years of age and older. In comparison, Advair is also approved for chronic obstructive pulmonary disorder (COPD) and contains a higher dose of salmeterol. Substitutable generic copies of Advair are still awaiting FDA approval.
AirDuo RespiClick is a breath-activated, multidose, dry-powder inhaler available in the strengths (fluticasone propionate / salmeterol) of 55 / 14 mcg, 113 / 14 mcg, and 232 / 14 mcg. Advair Diskus® (fluticasone propionate / salmeterol), powder for oral inhalation, is available in the strengths of 100 / 50 mcg, 250 / 50 mcg, and 500 / 50 mcg. Advair is also available as an aerosol for oral inhalation, Advair HFA®, in the strengths of 45 / 21 mcg, 115 / 21 mcg, and 230 / 21 mcg.
The launch of Teva’s AirDuo RespiClick coincided with the launch of their authorized generic version of the AirDuo product. Although this authorized generic version of AirDuo is also not directly substitutable with Advair, it is expected to result in increased competition as it is priced at a 68% to 80% discount to brand-name Advair. All three strengths of the AirDuo RespiClick carry an average wholesale price (AWP) of $342.00 per inhaler, and the AirDuo authorized generic carries an AWP of $112.50 per inhaler. In comparison, Advair has an AWP of $349.04 to $570.38 per inhaler, depending on the strength. NPS is planning to review AirDuo Respiclick and its authorized generic for placement on the national formularies.
FDA Issues Complete Response Letter for Arthritis Drug
Earlier this month, the FDA issued a complete response (CR) letter for the New Drug Application (NDA) for baricitinib (Olumiant®). Baricitinib was being reviewed for the treatment of moderate-to-severe rheumatoid arthritis (RA). A decision on the investigational agent was expected in January 2017, however the FDA review was extended by three months to allow for additional analyses. The CR letter states the application cannot be approved in its current state and requires additional clinical data to verify the most appropriate doses and more fully characterize safety concerns. A timeline for completion of these additional requirements has not been released, but the manufacturer has stated the timeline for a resubmission will be determined after discussions with the FDA.
The application reviewed included data from phase III trials evaluating the agent in RA patients compared to placebo, methotrexate, and the injectable biologic Humira® (adalimumab). As baricitinib is an oral once-daily JAK inhibitor, if approved, it would be expected to compete directly with the other JAK inhibitor Xeljanz® (tofacitinib). Baricitinib is also being evaluated for use in other inflammatory conditions including atopic dermatitis, systemic lupus erythematosus, and psoriatic arthritis.
For additional information on baricitinib, please view the manufacturers’ press release.
- FDA approves new psoriasis drug. FDA News Release. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm541981.htm. Updated February 15, 2017. Accessed April 20, 2017.
- Siliq [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; February 2017. http://www.valeant.com/Portals/25/Pdf/PI/Siliq-pi.pdf. Accessed April 25, 2017.
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- FDA approves new psoriasis drug. P&T Community. https://www.ptcommunity.com/news/20170216/fda-approves-new-psoriasis-drug. Updated February 15, 2017. Accessed April 20, 2017.
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- FDA approves first drug to treat tardive dyskinesia. FDA News Release. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm552418.htm. Updated April 11, 2017. Accessed April 19, 2017.
- Brauser D. FDA approves first treatment for tardive dyskinesia: valbenazine (Ingrezza). Medscape Medical News. http://www.medscape.com/viewarticle/878495. Updated April 11, 2017. Accessed April 19, 2017.
- Helfand C. Neurocrine nabs Ingrezza OK to kick-start tardive dyskinesia market, with Teva waiting in the wings. FiercePharma. http://www.fiercepharma.com/marketing/neurocrine-nabs-ingrezza-ok-to-kick-start-tardive-dyskinesia-market-teva-waiting-wings. Updated April 12, 2017. Accessed April 19, 2017.
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- Teva announces FDA approval of Austedo (deutetrabenazine) tablets for the treatment of chorea associated with Huntington’s disease. Teva Latest News. http://www.tevapharm.com/news/teva_announces_fda_approval_of_austedo_deutetrabenazine_tablets_for_the_treatment_of_chorea_associated_with_huntington_s_disease_04_17.aspx. Updated April 3, 2017. Accessed April 26, 2017.
- Helfand C. Neurocrine goes high -$60k-plus high – with price for new movement drug Ingrezza. FiercePharma. http://www.fiercepharma.com/marketing/neurocrine-goes-high-60k-plus-high-price-for-new-movement-drug-ingrezza. Updated April 26, 2017. Accessed April 26, 2017.
- FDA approves new drug to treat multiple sclerosis: First drug approved for primary progressive MS. FDA.gov. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm549325. Updated March 29, 2017. Accessed April 20, 2017.
- FDA extends review of application for Ocrevus. Roche Media Release. http://www.roche.com/media/store/releases/med-cor-2016-12-20.htm. Updated December 20, 2016. Accessed April 26, 2017.
- Helfand C. Look out, Biogen and Novartis. Roche’s Ocrevus is coming for your MS sales—big time, analyst predicts. FiercePharma. http://www.fiercepharma.com/pharma/look-out-biogen-and-novartis-roche-s-ocrevus-coming-for-your-ms-sales-big-time-analyst. Updated April 13, 2017. Accessed April 20, 2017.
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- FDA approves two hepatitis C drugs for pediatric patients. FDA.gov. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm551407. Updated April 7, 2017. Accessed April 20, 2017.
- Han, DH. First direct-acting antivirals approved for pediatric HCV patients. EMPR.com. http://www.empr.com/news/chronic-hepatitis-c-adolescents-ledipasvir-sofosbuvir/article/6492222. Updated April 7, 2017. Accessed April 20, 2017.
- Sovaldi [package insert]. Foster City, CA: Gilead Sciences; April 2017. https://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/sovaldi/sovaldi_pi.pdf. Accessed April 26, 2017.
- Harvoni [package insert]. Foster City, CA: Gilead Sciences; April 2017. https://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/sovaldi/sovaldi_pi.pdf. Accessed April 26, 2017.
- Lowes R. Global EpiPen Recall Now Includes United States. Medscape Medical News. http://www.medscape.com/viewarticle/878084. Updated March 31, 2017. Accessed April 3, 2017.
- Mylan Provides Update on Meridian Medical Technologies’, a Pfizer Company, Expanded Voluntary Worldwide Recall of EpiPen Auto-Injector. Recalls, Market Withdrawals, & Safety Alerts. U.S. Food & Drug Administration. https://www.fda.gov/Safety/Recalls/ucm550173.htm. Updated March 31, 2017. Accessed April 3, 2017.
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- Pressuring GSK’s Advair, Teva launches both AirDuo RespiClick and Authorized Generic. FiercePharma. http://www.fiercepharma.com/pharma/putting-pressure-advair-teva-launches-airduo-respiclick-and-authorized-generic. Updated April 20, 2017. Accessed April 26, 2017.
- Teva launches copy of asthma inhaler Advair. Reuters. http://www.reuters.com/article/teva-pharm-ind-asthma-idUSL3N1HS57G. Updated April 20, 2017. Accessed April 26, 2017.
- FDA Approves Copies of Advair and Flovent for Asthma Patients – Fully Substitutable Generics Await Approval. P&T Community. https://www.ptcommunity.com/news/20170130/fda-approves-copies-advair-and-flovent-asthma-patients. Updated January 30, 2017. Accessed February 21, 2017.
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- FDA declines to approve Eli Lilly and Incyte arthritis drug Olumiant. Reuters. http://www.reuters.com/article/us-lilly-incyte-fda-idUSKBN17G16Z. Updated April 17, 2017. Accessed April 26, 2017.
- FDA Issues Complete Response Letter for Baricitinib. Business Wire. http://www.businesswire.com/news/home/20170414005051/en/. Updated April 14, 2017. Accessed April 26, 2017.
- Hee Han D. FDA requires more data before baricitinib approval. EMPR.com. http://www.empr.com/drugs-in-the-pipeline/rheumatoid-arthritis-ra-baricitinib-jak-inhibitor/article/650726. Updated April 14, 2017. Accessed April 26, 2017.
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