FDA Approved Drugs: February 2020

The Express Scripts Office of Clinical Evaluation and Policy tracks some recent updates to the drug pipeline.
FDA Update

Ayvakit Approved to Treat Gastrointestinal Stromal Tumors

The FDA approved Ayvakit (avapritinib) tablets on Jan. 9, 2020. Ayvakit is indicated to treat adult patients who have inoperable or metastatic gastrointestinal stromal tumors (GIST) that have an exon 18 mutation in platelet-derived growth factor receptor alpha (PDGFRA). GIST is a type of soft tissue sarcoma affecting the lining of the gastrointestinal (GI) tract, most commonly the stomach or small intestines. It is diagnosed for between 3,000 and 6,000 American patients – usually older adults – each year. Approximately 10% of patients have GIST caused by a mutation, especially of exon 18, in PDGFRA, which is involved in cell differentiation, growth and replication. Exons are sections of DNA that carry information for specific proteins. Mutations in another gene, receptor tyrosine kinase (KIT), also may be involved. GIST that has such mutations is difficult to treat and it worsens relatively quickly. Ayvakit blocks the mutated PDGFRA and KIT kinases. Its recommended dose is 300mg taken once a day at least one hour before or two hours after eating. The manufacturer, Blueprint Medicines Corp., plans to launch it the week of Jan. 13, 2020. The wholesale acquisition cost (WAC) has been set at $32,000 for a 30-day supply. For full prescribing information, please look here.

New Keytruda Indication

On Jan. 9, 2020, Keytruda® (pembrolizumab - Merck) was FDA approved to treat high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). NMIBC affects about three-fourths of the 80,000 patients newly diagnosed with bladder cancer each year in the U.S. Initial treatment for it usually involves surgical removal of tumors and treatment with intravesicular (placed inside the bladder through a catheter) chemotherapy or a vaccine, Bacillus Calmette-Guérin (BCG). As many as one-half of NMIBC tumors will return within around one year after treatment, however; and eventually some cases no longer respond to BCG. Currently, the usual therapy for BCG-resistant patients at high risk of recurrence and progression to invasive cancer is removal of the bladder (cystectomy) and surrounding tissues. Keytruda will be used by itself for the 30% to 40% of patient who have bladder tumors that are BCG resistant and who cannot or choose not to have cystectomies. It will be given as 200mg doses in 30-minute long IV infusions once every three weeks for 24 months or until the cancer worsens or the patient cannot tolerate the drug’s side effects. First FDA approved in 2014, Keytruda is a human programmed death receptor-1 (PD-1)-blocking antibody that has additional previous indications for multiple other cancer types. Check here for its full prescribing information. 

Valtoco Approved to Treat Seizure Clusters

On Jan. 10, 2020, a new dosage form of diazepam, Valtoco® (diazepam nasal spray), C-IV, was FDA approved for patients at least six years old. It will be used as on-demand treatment for patients who have epilepsy and who experience seizure clusters and/or acute repetitive seizures that are different from their usual seizure patterns. The manufacturer, Neurelis, estimates that over 150,000 U.S. patients who have epilepsy also have the potential for periods of acute repetitive seizures. Dosed by the patient’s age and weight, Valtoco will be dispensed in cartons that contain either two individually blister-packed devices (for the 5mg and 10mg devices) or two blisters each containing two devices (7.5mg and 10mg). Caregivers should administer one dose as soon as a seizure cluster begins. If necessary, a second dose may be given at least four hours after the first one. No more than two doses should be used for each episode, Valtoco should not be used more than once in five days and it should not be used for more than five clusters in any 30-day period. All diazepam products carry a boxed warning cautioning about simultaneous use with opioids, which increases the risks of respiratory depression, sedation and death. It also is contraindicated for use in patients who have narrow-angle glaucoma. Neurelis has not announced its plans for pricing, but it intends to launch within the next two months. Here is full prescribing information.

Pfizer Announces the Launch of Zirabev

According to the Center for Biosimilars, Pfizer has introduced Zirabev(bevacizumab-bvcr), a biosimilar for Avastin® (bevacizumab - Genentech), to the U.S. market. Supplies are expected to be available the week of Jan. 13, 2020. FDA approved on June 27, 2019, Zirabev is indicated for treating metastatic or recurring cases of cervical cancer, colorectal cancer, glioblastoma, non-squamous non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). It is administered by IV infusion at doses and schedules that differ according to the cancer being treated. Its WAC is $613.40 for a 100mg vial and $2,543.60 for a 400mg vial, which is 23% less than the WAC for Avastin. Another Avastin biosimilar, Mvasi (bevacizumab-awwb - Allergan/Amgen), was launched in mid-July 2019. However, neither Mvasi nor Zirabev is considered to be a generic and neither is automatically interchangeable with Avastin or one another. Additionally, neither biosimilar is approved for three other Avastinindications (ovarian, fallopian tube, and primary peritoneal cancer), because they are protected by Orphan Drug Exclusivity (ODE).  Find full prescribing information for Zirabev here.

MedWatch Update

Belviq/Belviq XR

The FDA issued a safety communication on Jan. 14, 2020, for Belviq® (lorcaserin) tablets and Belviq XR® extended-release tablets. Originally approved in 2012 and 2016, respectively, they are used along with diet and exercise to manage weight for patients who are obese (a body mass index [BMI] of 30 kg/m2 or greater) or who are overweight (a BMI of 27 kg/m2 to30 kg/m2) and who also have other health issues, like diabetes and hypertension. In results from a recent clinical trial, taking a Belviq product may have been associated with more cases of cancer. The trial was not designed to evaluate cancer risk, however; and the possible link is not confirmed. Still, the FDA is advising patients to discuss other treatment options with their healthcare providers. Physicians should consider the possible risks for each patient before prescribing or continuing prescriptions for Belviq/Belviq XR. More information is in the FDA’s notice.

New Indication for Ozempic and Labeling Changes for Rybelsus

On Jan. 16, 2020, the FDA took action for two Novo Nordisk products. Both contain the same glucagon-like peptide-1 (GLP-1) receptor agonist, but in different dosage forms. Both are indicated to be used along with diet and exercise to manage blood sugar for adults who have type 2 diabetes. Like all GLP-1 agonists, they have a boxed warning about tumors of the thyroid gland (thyroid C-cell tumors) that have occurred among laboratory animals treated with some GLP-1 receptor agonists in preclinical studies. However, whether or not GLP-1s cause humans to develop thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), is not yet known. Patients with MCT, individuals with close family members who have thyroid C-cell tumors and patients with Multiple Endocrine Neoplasia syndrome type 2 (tumors in more than one gland) should not use them.

Ozempic® (semaglutide) injection for subcutaneous (SC) use was awarded a new indication to lower the chance of heart attacks, strokes and other major cardiovascular (CV) events for adults who have type 2 diabetes and CV disease. The approval was based on results from the SUSTAIN 6 CVOT clinical trial, which lasted for two years. Patients using Ozempic along with their prescribed diabetes and CV treatments averaged 26% fewer CV events than participants given a placebo along with their regular medications. Dispensed in single-dose self-injector pens, Ozempic is administered at a recommended dose of 0.5mg once a week. Here is its full prescribing information.

Rybelsus®(semaglutide) tablets are taken every morning with a small amount of water and at least one-half hour before any food at a recommended dose of 7mg. The dose may be increased to 14mg, if needed, after one month at the lower dose has not improved blood sugar adequately. The FDA is allowing Novo Nordisk to include results from a separate 3,000 participant trial, PIONEER 6 CVOT, evaluating the safety of Rybelsus and showing it was approximately equal to placebo in reducing CV events. Additionally, fewer patients taking Rybelsus died from any reason during the 16-month follow up after the study (23 vs 45 in the placebo group). All patients also continued receiving their usual therapy for CV and diabetes. Find prescribing information for Rybelsus here.

Tepezza Approved to Treat Thyroid Eye Disease

Tepezza (teprotumumab-trbw – Horizon Therapeutics) for injection was approved by the FDA on Jan. 21, 2020. It is the first drug indicated to treat a rare autoimmune condition, thyroid eye disease (TED), which also is called Graves’ ophthalmopathy. Frequently associated with Grave’s disease, a condition that involves overactivity of the thyroid gland, TED is believed to affect between 15,000 and 20,000 American adults. About five times as many women as men have TED, and it is far more common for patients who smoke or who are around secondhand smoke. Usually developing for patients in their 30s to 50s, TED involves the inflammation and overgrowth of tissues behind the eyes. As a result, the eyes develop a characteristic protrusion known as proptosis. Patients also may have swollen eyelids, irritated eyes, light sensitivity and double or blurred vision. By blocking insulin-like growth factor 1 receptors (IGF-1R), Tepezza helps to prevent inflammation and tissue growth behind the eyes. It will be given as one series of eight IV infusions, with the first at 10mg/kg of patient weight and the following seven at 20mg/kg. Infusions are spaced at three-week intervals. Horizon plans a launch within the next few weeks at a WAC of $14,900 per vial. For a patient weighing 70kg (154 pounds) 23 vials will be required for a full course of treatment (totaling $342,700 in WAC). For its complete prescribing information, look here.

The FDA Approves Tazverik for Epithelioid Sarcoma

The FDA announced on Jan. 23, 2020, that it approved Tazverik (tazemetostat – Epizyme) tablets. Tazverik is the first in a new class of drugs that block the activity of an enzyme, enhancer of zeste homolog 2 (EZH2) methyltransferase. It is approved to treat patients 16 years of age and older who have epithelioid sarcoma that has metastasized or spread locally and that cannot be removed by surgery. Sarcomas are cancers that start in connective tissues, such as bones and soft tissues, which include blood vessels, fat and muscles. Epithelioid sarcoma, which usually begins under the skin of the arms, fingers, hands, legs or toes, accounts for about one percent of the 13,000 cases of soft tissue sarcoma diagnosed in the United States each year. Adolescents and young adults are more likely to have its most common form (distal type). The usual treatment for epithelioid sarcoma is surgery to remove the tumors, but the condition is difficult to diagnose, so many patients have metastases or advanced cancer at diagnosis. Radiation and chemotherapy or targeted therapy with one of several other drugs FDA approved to treat soft tissue sarcomas may be used, as well. Tazverik is the first drug specifically developed for epithelioid sarcomas. By inhibiting EZH2, it increases production of tumor suppressor cells that reduce the growth of epithelioid tumors. Its recommended dose is 800mg (four tablets) taken twice a day. A Medication Guide that will be given to patients using Tazverik explains that it may cause other types of cancer and that it may damage developing babies. A woman of childbearing age should use contraceptives while she or her male partner takes Tazverik and for six months or longer after treatment ends. Epizyme plans to launch Tazverik by mid-February at a WAC of $15,500 for a one-month supply ($186,000 per year). Full prescribing information may be found here.

Second Rituxan Biosimilar Now Available in the U. S.

Ruxience(rituximab-pvvr), Pfizer’s biosimilar to Rituxan® (rituximab – Celgene), launched on Jan. 23, 2020. Approved by the FDA on July 23, 2019, it is indicated to treat adults who have non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL) or granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). A monoclonal antibody, it causes B cells to disintegrate by binding to CD20 proteins on their cell surfaces. Administered as IV infusions, it has to be given by a healthcare professional in a facility equipped to handle emergency treatment of serious side effects that it may cause. A boxed warning lists those potentially fatal adverse effects, which include adverse infusion-related responses, mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML) and reactivation of hepatitis B. Doses and dose schedules vary according to the condition under treatment and the patient’s response to therapy. Ruxience is not interchangeable with Rituxan or with Rituxan’s other biosimilar, Truxima® (rituximab-abbs – Celltrion/Teva), which was introduced to the U.S. market in November 2019. Ruxience has a WAC of $71.68 per 10mg, which is a 24% discount to the WAC of Rituxan. Full prescribing information for Ruxience is here.

New Dosage Form and Extended Indication for Dificid

On Jan. 24, 2020, the FDA approved an oral suspension formulation and an extended indication for the tablet form of Dificid® (fidaxomicin - Merck). An oral antibiotic that is absorbed only minimally into the body, it is indicated only to treat Clostridioides difficile (C diff)-associated diarrhea for patients at least six months old. Previously known as Clostridium difficile, C diff is a bacterium that infects the colon, particularly for patients who have used different antibiotics for other infections. Potentially fatal, it causes fever, nausea and diarrhea. An estimated one-half-million cases of C diff are reported in the U.S. each year. To treat it, Dificid will be administered as two doses per day for 10 days. For adults and children who can swallow tablets, each dose is one 200mg tablet; for those who weigh less than 12.5 kg (about 28 pounds) and/or who cannot swallow tablets, liquid doses are based on weight. A release date and pricing for the oral suspension have not yet been disclosed. Check here for Dificid’s prescribing information.

Trijardy XR FDA Approved

The FDA approved Trijardy XR extended-release tablets on Jan. 27, 2020. The first three-drug combination for managing diabetes, Trijardy XR combines metformin with Jardiance® (empagliflozin), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, and Tradjenta® (linagliptin), a dipeptidyl peptidase 4 (DPP4) inhibitor. Marketed jointly by Eli Lilly and Boehringer Ingelheim, all three branded drugs are indicated for the treatment of adults who have type 2 diabetes, as is metformin. Metformin reduces production of glucose, lessens its absorption and improves insulin sensitivity. SGLT2 drugs block reabsorption of glucose by the kidneys to increase glucose excretion in the urine. DPP-4 inhibitors decrease the activity of an enzyme that breaks down hormones that help to maintain blood glucose control. Including all three in one tablet is more convenient for patients who need more than one drug to control blood sugar. To be produced in four different strength combinations, Trijardy XR will be taken one time each day by patients who already are using diet, exercise and other diabetes drugs, but who still need more help to lower blood sugar levels. As with all drug products that include metformin, Trijardy XR carries a boxed warning and has a medication guide about the possibility that it may cause lactic acidosis — a rare, but potentially dangerous, accumulation of acids in the body. No launch or pricing plans are available. Here is prescribing information for Trijardy XR.

Auto-Injector Approved for Ajovy

Teva Pharmaceuticals USA received FDA approval on Jan. 27, 2020, for an auto-injector device for its calcitonin gene-related peptide (CGRP) inhibitor, Ajovy® (fremanezumab-vfrm). One of three injectable CGRP inhibitors that are FDA approved, Ajovy is used to prevent migraine headaches for adult patients. Auto-injectors containing 225mg of Ajovy are expected to launch within the coming months. Its recommended dosing is one SC injection (225mg) every month or three injections (675mg) all at the same time once every three months. Prefilled 225mg syringes remain available, as well. Prescribing information for Ajovy is here.

MedWatch Update


An updated safety communication for clozapine was issued by the FDA on Jan. 28, 2020. A medication used for treating schizophrenia, clozapine is available as generics and as the brand names, Clozaril® (HLS Therapeutics USA) tablets and Versacloz® (TruPharma) Oral Suspension. The FDA is intensifying its previous warning that constipation often associated with taking clozapine may cause rare bowel blockages and other severe bowel problems. Although constipation is a common side effect of taking clozapine, some patients needed to be hospitalized, had to have surgery or died due to infections or blockages they developed while taking it. Most seriously affected patients were taking higher doses of clozapine and many were using other medications, such as opioid pain relievers and overactive bladder drugs, that also slow down activity in the intestines. Prescribers should consider recommending a laxative along with clozapine, they should inform patients how to avoid constipation and they should check for problems at patient visits. Patients should know the signs of constipation and report any major changes in bowel habits to their doctors. Labeling for all clozapine products will include a stronger warning. The products already are prescribed and dispensed under a risk evaluation and mitigation strategy (REMS), which requires special training for clinicians and registration for all patients. FDA’s notice can be found here.

Palforzia Approved for Peanut Allergy

On Jan 31, 2020, the FDA approved Palforzia™ [peanut (Arachis hypogaea) allergen powder-dnfp] capsules and sachets from Aimmune Therapeutics. It is an immunotherapy to be taken orally for preventing severe allergic reactions (anaphylaxis) to peanuts for children ages four to 17 who have diagnosed peanut allergies. Patients still will have to avoid eating or being around products that contain peanuts and keep emergency treatments at hand, but using Palforzia may help prevent or decrease reactions if peanuts are encountered accidentally. Treatment is in three stages – on the first day, 13mg will be administered in gradually larger amounts, then doses will be increased progressively over several months from 3mg/day to a maintenance dose of 300mg per day – about the same amount of protein as in one peanut. Capsules and sachets contain peanut powder that should be sprinkled onto cold, soft food, such as applesauce or yogurt, and consumed immediately. The first doses at each increasing dose level will be given in a healthcare facility staffed and equipped to manage severe allergic reactions. A boxed warning on the labeling cautions that Palforzia, itself, could trigger anaphylaxis. A REMS for Palforzia will restrict its use to providers who are certified to prescribe and dispense it. Patients must be registered to receive it. Launch is projected for the first quarter of 2020 at a monthly WAC of about $890. Look here for full prescribing information.

Reyvow Launched

After receiving a C-V controlled substance designation from the U.S. Drug Enforcement Agency (DEA), Eli Lilly and Company launched Reyvow™ (lasmiditan) tablets on Jan. 31, 2020. FDA approved in October, 2019, it is the first in a new class of oral drugs, known as serotonin (5-HT) 1F receptor agonists (ditans), that are indicated for treatment of adults who have acute migraine headaches. Recommended dosing for Reyvow is 50mg, 100mg or 200mg taken once a migraine has started. No more than one dose should be taken per day and no safety information is available for using more than four doses in a one-month period. Because it may cause sleepiness, patients are advised to wait at least eight hours after taking it before driving or doing other tasks that require mental alertness. Reyvow is marketed in packages of eight tablets – two blister cards containing four tablets each – at a WAC of $640. Its prescribing information is here.

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