FDA Approved Drugs: May 2020

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

Hemophilia Treatment Sevenfact Approved

On April 1, 2020, the FDA approved Sevenfact® [coagulation factor VIIa (recombinant)-jncw] to control bleeding for patients at least 12 years old who have hemophilia A or B with inhibitors. In the U.S., an estimated 20,000 people are living with hemophilia. Because males have a greater likelihood of inheriting a copy of the hemophilia gene if their single X chromosome is affected, most patients are male.. The active ingredient in Sevenfact is factor VIIa (FVIIA), which is produced using milk from genetically engineered rabbits. Factor VIIa controls bleeding episodes through bypassing the parts of the coagulation pathway that are blocked by inhibitors. It is not approved to prevent bleeds. During a clinical trial, Sevenfact was shown to be safe and effective when used by 27 patients who had hemophilia A or B with inhibitors. In the study, 465 mild-to-moderate bleeds and three severe episodes were treated successfully with Sevenfact. After 12 hours, about 86% of the treated bleeding required no further treatment, and patients reported no increase in pain. Recommended dosing for mild or moderate bleeding episodes is 75mcg/kg given by intravenous (IV) infusion once every three hours until bleeding stops. Alternately, an initial dose of 225mcg/kg may be administered; if bleeding is not resolved within 9 hours, 75mcg/kg may be given once every three hours until bleeding stops. For severe bleeding, the suggested initial dose is 225mcg/kg. If bleeding continues after six hours, a dose of 75mg/kg can be repeated every two hours. Labeling for Sevenfact has a boxed warning that patients using it should be watched for signs of blood clots. The manufacturer, Laboratoire Francais du Fractionnement et des Biotechnologies S.A. (LFB S.A.), is delaying launch until late-2020, at the earliest, due to the COVID-19 pandemic. For full prescribing information, look here.

MedWatch Update

Ranitidine

After alerts that it issued last fall, the FDA decided on April 1, 2020, to ask all manufacturers of products containing ranitidine to remove their products from the market. An oral histamine-2 (H2) blocker, ranitidine was available both with and without a prescription. Sold under the brand-name, Zantac® (Chattem, a subsidiary of Sanofi-Aventis), and numerous generics, it was widely used to treat gastroesophageal reflux disease (GERD), heartburn and stomach ulcers. The FDA discovered that  amounts of a suspected cancer-causing substance, N-nitrosodimethylamine (NDMA), that were found in samples of ranitidine, increase while the drugs are in storage --- particularly at temperatures higher than room temperature. Although the amounts still are small, the FDA feels the levels are unacceptable for patients to use. Multiple other drugs, including other H2 blockers, such as cimetidine and famotidine; and proton pump inhibitors (PPI), such as esomeprazole and lansoprazole, do not contain unacceptable amounts of NDMA. Patients taking a non-prescription form of ranitidine are advised to stop using it. Those who were prescribed ranitidine should talk about alternative treatments with their doctors before discontinuing the drug. All supplies of ranitidine that individuals have should be put into a sealable plastic bag with wet trash, such as used coffee grounds, and thrown away. Additional information is in the FDA’s notices and their Question and Answer page.

Reblozyl Approved for Second Indication

Bristol Myers Squibb and Acceleron Pharma’s Reblozyl® (luspatercept-aamt) gained approval for a second indication from the FDA on April 4, 2020. Reblozyl, an erythroid maturation agent (EMA), was first approved on Nov. 8, 2019, to treat anemia for adult patients who have beta thalassemia and who need regular transfusions of red blood cells (RBCs). The new approval is to treat anemia for adults who have tried an erythropoiesis stimulating agent (ESA), such as Epogen® (epoetin alfa – Amgen), but who still require two or more units of RBCs over eight weeks to treat very low to intermediate risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T). For MDS-RS and MDS/MPN-RS-T, Reblozyl is given as subcutaneous (SC) injection once every three weeks at a starting dose of 1mg/kg. The dose may be increased at specified intervals if the patient’s need for transfusions does not decrease. Reblozyl should be discontinued if the need for RBC transfusions hasn’t lessened after three doses at the highest recommended level. However, it is not to be substituted for transfusions if patients require immediate correction of anemia. Doses may be reduced or delayed if the patient’s hemoglobin levels increase. Approval for the new indication was based on MEDALIST, a phase III trial of 229 patients randomized to Reblozyl or placebo every three weeks for 24 weeks or until disease progression, toxicity or loss of efficacy. Results showed that 38% of patients treated with Reblozyl did not need transfusions for eight weeks or longer vs 13% of participants in the placebo group. For full prescribing information click here.

Controlled Substance Designation Removed for Epidiolex

In a press release dated April 6, 2020, GW Pharmaceuticals disclosed that the U.S. Drug Enforcement Agency (DEA) has removed Epidiolex® (cannabidiol) oral solution from the federal schedule of controlled substances. FDA approved in June 2018, Epidiolex is a marijuana derivative sold in the U.S by GW’s subsidiary, Greenwich Biosciences. Even though Epidiolex does not have the psychoactive (mood or behavior changing) properties of marijuana, the DEA assigned it to the lowest level of controlled substance (C-V) before it launched in November 2018. It is used to treat children two years of age and older with Lennox-Gastaut syndrome or Dravet syndrome, which are rare forms of epilepsy. Once the individual states follow the national policy of descheduling Epidiolex, it will be easier for caregivers of patients to obtain. Prescriptions will be valid for one year (or in accordance with state laws) instead of six months and they will not have to be recorded under states’ prescription drug monitoring programs. For its complete information, look here.

New Indication for Braftovi

Braftovi® (encorafenib), an oral small-molecule kinase inhibitor marketed in the United States by Pfizer, was given a new FDA indication on April 8, 2020. It is approved, in combination with Erbitux® (cetuximab – Eli Lilly) solution for injection, for previously treated patients who have metastatic colorectal cancer (CRC) that tests positive for BRAFV600E mutations. According to American Cancer Society (ACS) estimates, about 148,000 cases of CRC will be diagnosed in the U.S., this year; and around 15% of patients have BRAF mutations. In the BEACON CRC clinical trial, 20% of patients taking Braftovi and using Erbitux responded to therapy as compared with 2% of patients who used the current drugs of choice -- Erbitux with either irinotecan or FOLFIRI, a multi-drug chemotherapy (chemo) regimen. Overall survival (OS) for patients treated with the new combination was three months longer (8.4 months vs 5.4 months) than for patients using current standards of care. Dosing for CRC is 300mg (four capsules) taken one time each day. In combination with Mektovi® (binimetinib - Pfizer), Braftovi also is approved to treat BRAF-mutated metastatic or inoperable melanoma. The FDA expedited approval for the new indication under its Priority Review and Breakthrough Therapy programs. Here is updated prescribing information.

First Generic Approved for Proventil HFA

On April 8, 2020, the FDA) approved Cipla’s albuterol metered–dose inhaler (MDI), 90mcg — the first AB-rated generic for Proventil® HFA (Merck) inhalation aerosol. Used to treat and prevent bronchospasms due to exercise or reversible obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease, it is indicated for patients four years of age and older. To prevent exercise-induced bronchospasms, patients use two oral inhalations about 15 minutes before beginning to exercise. Small children may require only one inhalation. To relieve bronchospasms, the recommended dose usually is two inhalations every four to six hours, but some patients may need more inhalations at shorter intervals for serious acute episodes. For most patients, total doses should be limited to 12 inhalations per day. Albuterol is a short-acting beta2 agonist (SABA) typically used as-needed to relieve asthma symptoms. It is not meant for regular chronic use. Cipla plans to begin releasing supplies of the generic in stages. In Feb. 2020, the FDA approved Perrigo’s A-rated generic to ProAir® HFA (albuterol inhalation aerosol – Teva). While small supplies of the generic are being launched, the company is working to increase production to full capacity by the fourth quarter of 2020. Although other albuterol inhalers are sold in the U.S., shortages have occurred as they are being used to help treat some patients who have COVID-19. To accelerate the development of inhaled albuterol products, the FDA recently issued specific guidelines for manufacturers. Cipla indicates that it will donate some part of its generic stock to the effort to control COVID-19.

Koselugo Approved to Treat Neurofibromatosis Type 1

The FDA approved Koselugo® (selumetinib) capsules on April 10, 2020, to treat neurofibromatosis type 1 (NF1). A rare genetic condition caused by mutations in specific genes that control cell formation in the nervous system, NF1 results in small, slow-growing, non-cancerous tumors around nerves, on the skin or just underneath the skin. NF1 affects one in 3,000 to 4,000 patients in the United States, or about 100,000 individuals. Although some patients are diagnosed at birth, others develop signs and symptoms over years – with most patients diagnosed before they are 10 years old. Up to one-half of cases are due to spontaneous mutations; the patients have no family history of the disease, but the affected patients may pass it to their children. As many as 50% of patients who have NF1 progress to plexiform neurofibromas (PN) -- larger, spongy tumors along main nerves and their branches. Due to their size or placement, many PNs cannot be removed by surgery. Koselugo inhibits mitogen-activated protein kinase (MEK), an enzyme that promotes the growth and spread of tumor cells. Indicated as treatment for pediatric patients at least two years old, Koselugo is the first drug approved to treat any form of NF1. Dosing is based on the body surface area of the patient. With most children taking 25mg/m2 approximately every 12 hours, total daily doses may be adjusted to as little as 30mg/day for smaller patients or up to 100mg/day for larger ones. AstraZeneca will produce and distribute Koselugo, but profits will be shared by Merck under a collaboration agreement. Launched soon after approval, it costs approximately $130,000 per year. Look for complete Koselugo prescribing information here.

First Urothelial Cancer Drug, Jelmyto, Approved

UroGen Pharma received FDA approval on April 15, 2020, for Jelmyto (mitomycin gel) for pyelocalyceal solution. It is an alkylating agent indicated to be instilled by a urologist into the upper urinary tract to treat adults who have low-grade upper tract urothelial carcinoma (LG-UTUC). UTUC accounts for about 5% to 10% of the estimated 62,000 new cases of urothelial cancer diagnosed each year in the United States. It is two to three times more common among men as women and approximately 90% of patients are white. Up to 50% of UTUC is low-grade. Before treatment with Jelmyto begins, patients need to have a pyelography (an x-ray of the urinary tract) to determine the size of the upper urinary tract, which includes the ureters and the parts of the bladder and the kidneys where ureters attach (the bladder cuff and the renal pelvis, respectively). Recommended dosing is 4mg per mL of upper urinary tract volume, but no more than 60mg should be used for a single dose. Doses may be administered through a urinary catheter or a nephrostomy tube (a thin tube inserted through the back into the renal pelvis). The first six doses are given on one-week cycles and then treatment is evaluated. If tumors still are present, treatment is stopped. If tumors have disappeared, patients continue receiving instillations on a monthly schedule for up to 11 additional instillations. Jelmyto will be packaged in cartons of two vials containing 40mg each of mitomycin powder and one vial with 20mL of the hydrogel that is used to liquefy the powder. It is expected to be available on June 1, 2020. Jelmyto will cost approximately $21,000 per dose. No other drugs currently are available to treat LG-UTUC. Some LG-UTUC tumors may be removable by endoscopic procedures; but many tumors, especially small ones, are difficult to find in the upper urinary tract making their removal difficult. Additionally, LG-UTUC has a high rate of recurrence. Jelmyto’s full prescribing information may be found here.

Biosimilar to Herceptin – Ontruzant – Launched in US

Merck launched Ontruzant® (trastuzumab-dttb), a biosimilar to Herceptin® (trastuzumab - Genentech), on April 15, 2020. Approved by the FDA on January 18, 2019, Ontruzant was developed through a collaboration between Merck and Samsung Bioepis. Like Herceptin and its other FDA-approved biosimilars, it is indicated to treat breast cancers and metastatic stomach cancers (gastric or gastroesophageal junction adenocarcinomas) that overexpress the HER2 gene (HER2+). Recommended doses vary according to the cancer being treated. Ontruzant’s wholesale acquisition cost (WAC) is a 15% discount to Herceptin. Therefore, the average wholesale acquisition cost (WAC) will be $1,325 for 150mg single dose vials and $3,709 for 420mg multiple dose vials, approximately. All trastuzumab products have boxed warnings that they may cause birth defects, heart failure, respiratory collapse or severe allergic reactions. Ontruzant faces competition from Herceptin and its previously FDA-approved biosimilar products – Ogivri® (trastuzumab-dkst – Mylan/Biocon), Herzuma® (trastuzumab-pkrb – Celltrion/Teva), Kanjinti® (trastuzumab-anns – Amgen) and Trazimera® (trastuzumab-qyyp – Pfizer), which were previously launched. None of the biosimilar products are interchangeable with Herceptin or another biosimilar. Merck has announced that it will spin-off its biosimilar products, including Ontruzant, to a new company in 2021. Prescribing information for Ontruzant can be found here.

Tukysa Approved for Breast Cancer

On April 17, 2020, the FDA approved Seattle Genetics’ Tukysa (tucatinib) tablets in combination with trastuzumab (Herceptin® - Genentech, biosimilars) and capecitabine (Xeloda® - Genentech) for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients whose cancer has spread to the brain, and who have received one or more prior anti-HER2-based regimens in the metastatic setting. Tukysa is an oral tyrosine kinase inhibitor with a recommended dose of 300mg twice daily. FDA approval of Tukysa was based on a clinical study that found patients who were treated with Tukysa, trastuzumab and capecitabine had an improvement in progression-free survival (amount of time with no tumor growth) of 7.8 months compared to 5.6 months for patients who received placebo, trastuzumab and capecitabine. Overall survival in the treatment group was 21.9 months compared to 17.4 months in the placebo group. For patients with brain metastases, the addition of Tukysa reduced the risk of cancer progression or death by 52% compared to trastuzumab and capecitabine alone. Seattle Genetics launched Tukysa within the week it was approved. The wholesale acquisition cost (WAC) for a one-month supply is $18,500. For full prescribing information, look here.

FDA Approves Pemazyre to Treat Cancer of the Bile Ducts

Incyte Pharmaceuticals received approval from the FDA for Pemazyre (pemigatinib) on April 17, 2020. It is an oral kinase inhibitor for treating adults who have cancer of the bile ducts (cholangiocarcinoma) that has been treated previously, but that has spread locally or metastasized and that cannot be removed surgically. No other targeted drugs are available specifically to treat cholangiocarcinoma. Before therapy begins, patients will be tested with Foundation Medicine’s FoundationOne®CDx, a companion diagnostic for the presence of fibroblast growth factor receptor 2 (FGFR2) rearrangements, including fusions. According to the American Cancer Society (ACS), about 8,000 Americans are diagnosed with cholangiocarcinoma annually. Between 9% and 14% of cases have mutations in FGFR2. Pemazyre, which targets FGFR, is taken on continuing 21-day cycles, at a recommended dose of one 13.5mg tablet daily for 14 days, followed by no treatment for the next seven days. Doses may be reduced for patients who experience serious adverse effects. Therapy ends when the cancer worsens or the drug’s side effects become intolerable for the patient to continue. Incyte plans an immediate launch at an estimated wholesale acquisition cost (WAC) of $24,600 per month. Look here for complete prescribing information.

Trodelvy Approved for Triple Negative Breast Cancer

Trodelvy (sacituzumab govitecan-hziy) was approved by the FDA on April 22, 2020.  An antibody-drug conjugate manufactured by Immunomedics, it is indicated to treat adults who have metastatic triple negative breast cancer (mTNBC) that already has been treated two or more times. It is the first drug attracted specifically to tumor-associated calcium signal transducer 2 (Trop-2) receptors. Once attached, it then releases a topoisomerase inhibitor that destroys cancer cells. The recommended dose for treating mTNBC is 10mg/kg administered as IV infusions on the first and eighth days of 21-day cycles. Due to the possibility of serious side effects that can include neutropenia (very low numbers of specific white blood cells) and severe diarrhea, Trodelvy has a boxed warning on its labeling. Patients should be observed during each infusion and for at least one-half hour after every treatment. It launched right away and will be available at a WAC of $2,012.50 for one single-dose vial containing 180mg of powdered Trodelvy. For full prescribing information, look here.

Ongentys, New Parkinson’s Disease Drug, FDA Approved

On Apr. 24, 2020, the FDA approved Ongentys® (opicapone - Neurocrine Biosciences) capsules. It is a selective catechol-O-methyltransferase (COMT) inhibitor for use as an add-on therapy to levodopa/carbidopa for patients who have Parkinson's disease (PD) and who are experiencing "off" episodes. PD is the second most common neurodegenerative disease in the U.S. behind Alzheimer’s disease. An estimated  one million Americans have PD. Of them, about 350,000 are taking levodopa/carbidopa, the gold standard of treatment. During advanced stages of PD, a patient may experience motor fluctuations between doses of carbidopa/levodopa, such as tremor, slowed movement or trouble walking, referred to as “off” episodes. The recommended dose of Ongentys is 50mg orally once per day at bedtime. Patients should not eat food for one hour before or one hour after taking Ongentys. It will be available in 25mg and 50mg capsules with a launch planned for later in 2020. Full prescribing info can be found here.

Jublia Gets Pediatric Indication

Ortho Dermatologic’s Jublia® (efinaconazole) Topical Solution, 10%, which first was FDA approved in June 2014 to treat adults, now can be used for children age six and older. It is an antifungal drug that is applied directly to affected toenails for treatment of treat distal lateral subungual onychomycosis (toenail fungus) caused by certain Trichophyton species. Generally beginning with discoloration, untreated toenail fungus can lead to foot infections and permanent damage of the affected nails. Through a unique bottle and brush device, Jublia is applied to clean, dry toenails. The entire nail, including the edges and underneath, should be covered with medication once a day for 48 weeks. The FDA awarded the new indication on April 26, 2020, based on results from a study that showed a 40% complete cure rate among 62 pediatric patients treated for one year. Revised prescribing information is here.

Ajovy Auto-Injectors Now Available

Teva Pharmaceuticals USA announced on April 27, 2020, that it has released Ajovy® (fremanezumab-vfrm) auto-injection devices. Indicated to prevent, but not to treat, migraine headaches for adults, Ajovy is a humanized monoclonal antibody. It inhibits the activity of calcitonin gene-related peptide (CGRP), a protein that causes blood vessels to tighten and trigger migraines. Since its FDA approval in September 2018, Ajovy has been marketed only as single-dose, prefilled syringes. Recommended dosing is one SC injection (225mg) once a month or three injections (775mg) at the same time once every three months. Check here for its complete prescribing information.

Final FDA Approval for Bafiertam

On April 28, 2020, the FDA granted final approval of Banner Life Science’s Bafiertam (monomethyl fumarate) delayed-release capsules. It is indicated for the treatment of adults who have relapsing forms of multiple sclerosis (MS), including isolated syndrome, relapsing-remitting disease (RRMS) and active secondary progressive disease (SPMS). MS is an autoimmune disease caused by inflammation in the central nervous system (CNS). It includes periods of active symptoms, such as problems with vision, balance, pain, weakness or numbness, which can be followed by episodes of remission. Nearly one million people are living with MS in the United States and RRMS affects around 85% of all patients diagnosed with it. To treat it, Bafiertam capsules should be swallowed whole, irrespective to food, with a starting dose of 95mg twice daily for one week; followed by an increase to the maintenance dose of 190mg (two 95mg capsules) twice daily. Since Bafiertam can damage the liver or decrease lymphocyte production, blood tests should be taken prior to starting therapy and every six to 12 months during treatment. Bafiertam was given tentative FDA approval as a new drug in 2018 via the 505(b)(2) pathway. Although it is not a direct therapeutic equivalent to Tecfidera® (dimethyl fumarate - Biogen), legal proceedings delayed full approval until a United States District Court of Appeals found in favor of Banner Life Sciences. Price and launch information is not available at this time. Full prescribing information can be found here.

FDA Expands Zejula Indication 

Zejula™ (niraparib - GlaxoSmithKline) was initially FDA approved on March 27, 2017, as maintenance treatment for women who responded at least partially to platinum-based chemo for recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer. It is a poly ADP-ribose polymerase (PARP) inhibitor, a class of drugs that destroys cancer cells or limits their growth by interfering with an enzyme cancer cells need to repair damage caused by drug treatment. Zejula does not require testing for a biomarker, such as BRCA gene mutations, like other PARP inhibitors do. On April 29, 2020,  it received a new indication under the FDA’s Real-Time Oncology Review. It now is approved as first-line, monotherapy  maintenance for women who have advanced cases of one of the cancers it targets and who have had a complete or partial response to first-line chemo, regardless of biomarker status. Previously, PARP inhibitor treatment was reserved only for patients whose cancers tested positive for BRCA mutations. Recommended dosing for Zejula is either 200mg (two capsules) or 300mg (three capsules) orally once a day depending on the patient’s weight and/or platelet count. Therapy continues until the cancer worsens or the drug’s side effects become to harsh for the patient. Here is revised prescribing information.

New Dosing for Keytruda

Based on information from previous clinical trials, Merck’s Keytruda® (pembrolizumab) was granted a new dosage schedule by the FDA on April 28, 2020. Keytruda is a human programmed death receptor-1 (PD-1)-blocking antibody that is given as a 30-minute IV infusion. FDA approved as both a single agent and in combination with other drugs to treat multiple types of cancer, it previously was recommended only for a 200mg dose once every three weeks. Now, doses can be higher (400mg) and further apart (once every six weeks) for adults who are being treated for any of its labeled indications. Because the new regimen was granted under the FDA’s Accelerated Approval program, additional confirmatory trials that demonstrate a clinical benefit may be needed before full FDA approval. For Keytruda’s complete prescribing information, look here.


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