FDA Approved Drugs: June 2020

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

Imbruvica Indication Extended

An oral Bruton’s tyrosine kinase (BTK) inhibitor, Imbruvica® (ibrutinib – Pharmacyclics) was approved by the FDA on April 21, 2020, to be used in combination with rituximab for initial treatment of adult patients less than 70 years old who are newly diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Rituximab, an intravenous (IV) monoclonal antibody, is available as the brand, Rituxan® (Genentech) and two biosimilars, Ruxience(rituximab-pvvr – Pfizer) and Truxima® (rituximab-abbs – Celltrion/Teva). Since its first FDA approval to treat mantle cell lymphoma (MCL) in November 2013, Imbruvica also has gotten additional approvals for treating chronic graft-versus-host disease (cGvHD) and other cancers, including Waldenström’s macroglobulinemia (WM). It also has previous CLL/SLL indications either as monotherapy, along with Gazyva® (obinutuzumab - Roche) or with bendamustine and rituximab. Whether or not it is used alone, recommended dosing is 420mg once daily with water. Imbruvica’s updated prescribing information is here.

FDA Approves Fensolvi

Tolmar Pharmaceuticals announced that the FDA approved Fensolvi® (leuprolide acetate) for injectable suspension on May 1, 2020. Fensolvi is a gonadotropin releasing hormone (GnRH) agonist used to treat pediatric patients two years of age and older who have central precocious puberty (CPP). CPP is early onset puberty caused by GnRH released in the brain, which in turn, stimulates the pituitary gland to release gonadotropin and physically mature the child’s reproductive organs and physical features. Patients with CPP can have diminished bone growth, psychological problems and emotional comorbidities. Fensolvi, which needs reconstitution prior to administration, will be available in kits containing 45mg of leuprolide. It is injected subcutaneously (SC) once every six months by a healthcare professional. Fensolvi is not substitutable with generic and brand alternative options of injectable leuprolide that are available. Approval was based on a multi-center, open-label, single-arm phase III trial of 64 children who have CPP. At six months after the first injection, 87% of children met the primary endpoint for serum luteinizing hormone (LH) concentration of less than 4IU/L. LH, regulated by GnRH, LH is released from the pituitary gland to trigger reproductive hormones. Also observed were suppressed sex hormones to pre-puberty levels and diminished or reversed clinical signs of puberty. Most common side effects were injection site pain/redness, fever, headache and sore throat. Price is not available at this time. Fensolvi was launched near the end of May 2020 at a wholesale acquisition cost (WAC) of $27,093 per kit containing one dose and the syringes and diluent needed for administration. Full prescribing information is here.

Darzalex Faspro Receives FDA Approval

Darzalex Faspro (daratumumab/hyaluronidase-fihj), a SC dosage form of Janssen’s IV antibody, Darzalex® (daratumumab), was FDA approved on May 1, 2020. It has indications, either alone or along with other cancer drugs, to treat adults who have multiple myeloma. Dosing schedules differ according to the type and stage of multiple melanoma, the patient’s prior treatment status and the other drugs being used. Daratumumab works by sticking to CD38 glycoproteins that accumulate on the surfaces of multiple myeloma and other cancer cells; causing cancer cells to break up while also promoting immune responses. The new SC form showed comparable effectiveness to the original form, but it can be administered in only a few minutes as compared to several hours for an IV dose. Both forms require pre-treatment and post-treatment with other drugs, though; and both forms must be given by a healthcare provider in a facility equipped to manage severe reactions that may occur. In clinical trials, Darzalex IV caused infusion reactions about 34% of the time versus a 13% rate for those using Darzalex Faspro. The new dose form will be introduced onto the U.S. market in mid-May as single-dose vials containing 1,800mg of daratumumab and 30,000 units of hyaluronidase, which allows for fast injection of the drug. Prescribing information is here.

New Indication for Farxiga

On May 5, 2020, AstraZeneca announced that a new indication was FDA approved for Farxiga® (dapagliflozin) tablets to reduce the risk of CV-related death and hospitalization in adults who have heart failure (NYHA class II to IV) with reduced ejection fraction with or without type 2 diabetes (DM2). The New York Heart Association (NYHA) classifies heart failure based on limitations of physical activity. An estimated 6 million people in the U.S. have heart failure and one-half of them have reduced ejection fractions -- a smaller than normal percentage of blood leaving the heart each time it contracts. Farxiga is a sodium-glucose cotransporter 2 (SGLT2) inhibitor first approved for blood sugar control, in addition to diet and exercise, for patients who have DM2. Later, it was approved to reduce hospitalization risk in heart failure patients who have both DM2 and established CV disease or multiple CV risk factors. Although other SGLT2 inhibitors have CV indications, Farxiga is the first approved to treat reduced ejection fraction in heart failure. The FDA granted Farxiga Priority Review and Fast Track designations for this new indication. FDA approved it from results of the Phase III DAPA-HF trial, in 4,744 adult patients who have heart failure and reduced ejection fraction. Patients were treated with the standard of care, in addition to Farxiga 10mg or placebo orally once daily. Compared to placebo, study results showed a 26% reduction in CV death or hospitalization. For more material, see the prescribing information here.

Truxima Now Approved for Additional Indications

Originally FDA approved only to treat adults who have CLL or some types of CD20-positive, B-Cell non-Hodgkin’s lymphoma (NHL), Truxima now has two more indications. Through a patent settlement agreement, it can be used to treat rheumatoid arthritis (RA) and granulomatosis with polyangiitis and microscopic polyangiitis (GPA/MPA). For RA, methotrexate also will be taken and Truxima will be given on 24-week cycles with one 1,000mg infusion followed by a second infusion two weeks later. If needed, the next cycle can begin after 16 weeks. Treatment for GPA/MPA involves a once-weekly, weight-determined dose for four weeks, two 500mg doses that are two weeks apart and then one 500mg infusion once every six months. Rituximab products must be given by healthcare providers in facilities that are equipped and staffed to handle severe adverse effects. A boxed warning on their labeling lists potentially fatal side effects, including infusion-related reactions, mucocutaneous (skin and mucus membrane) reactions, progressive multifocal leukoencephalopathy (PML) and reactivation of hepatitis B. Ruxience, the other rituximab biosimilar currently available in the U.S. does not yet have an indication for RA. Neither biosimilar is approved to treat pemphigus vulgaris (PV), an indication that the brand drug received in 2018. Here is revised prescribing information for Truxima.

Tabrecta Approved to Treat Certain Non-Small Cell Lung Cancers

The FDA approved Tabrecta (capmatinib – Novartis) tablets on May 6, 2020. A kinase inhibitor, it is the first drug indicated to treat adult patients who have metastatic or inoperable non-small cell lung cancer (NSCLC) that has a specific mutation -- exon 14 skipping -- in the mesenchymal-epithelial transition (MET) gene. NSCLC accounts for about 85% to 90% of the 230,000 cases of lung cancer diagnosed in the U.S. each year. Between 3% and 5% of metastatic NSCLC has mutations that cause exon 14 skipping in the MET gene (METex14). Novartis expects 4,000 to 5,000 Americans will be candidates for treatment with Tabrecta, annually. After a diagnostic test verifies the mutation, patients will take 400mg of Tabrecta twice a day. In the phase II clinical trial that lead to approval, 68% of treatment-naïve patients and 41% of previously treated patients responded at least partially to Tabrecta therapy. Response lasted at least one year for 47% of the patients new to treatment and 32% of those who had prior therapy. Because it may damage the liver, patients taking Tabrecta should have liver function tests before and during treatment. It also may inflame or scar the lungs, harm developing babies and increase sensitivity to sunlight. Its WAC is $17,950 for a four-week supply, but a launch date is not yet known. Look here for full prescribing information.

Retevmo Approved for RET-Mutated Lung and Thyroid Cancers

The Loxo Oncology division of Eli Lilly and Company received FDA approval for Retevmo (selpercatinib) capsules on May 8, 2020. Approval was granted for its use by patients who have one of three types of RET-positive (RET+) cancers. It treats adults who have metastatic RET+ NSCLC. It also is indicated for patients at least 12 years old who require systemic treatment for RET+ metastatic medullary thyroid cancer (MTC) or advanced RET+ thyroid cancer that cannot be managed by radioactive iodine (RAI). Around 2% of NSCLC cases, 10% to 20% of papillary thyroid cancers and 60% to 90% of patients with MTC have an RET fusion or mutation. Patients will be tested for RET mutations before Retevmo therapy begins. Dosing depends on body weight with 120mg twice daily recommended for patients weighing 50kg (110 pounds) or less and 160mg twice daily for those who weigh more than 50kg. It launched within one week of its approval. WAC has been set at $20,600 for a 30-day supply. Currently, no other drugs are approved specifically for RET mutations; but Blueprint Medicines’ pralsetinib is pending approval for the treatment of RET+ NSCLC. FDA approval is expected by Dec. 1, 2020. Complete prescribing information for Retevmo may be found here.

New Indications for Lynparza

A new indication for AstraZeneca’s poly ADP-ribose polymerase (PARP) inhibitor, Lynparza® (olaparib) tablets, was approved by the (FDA on May 8, 2020. It can now be used as initial maintenance therapy, in combination with bevacizumab, for advanced ovarian, fallopian tube or primary peritoneal cancers that are positive for homologous recombination deficiency (HRD). An estimated 50% of the cancers covered by the new indication have an HRD, which must be verified by a diagnostic test for deleterious BRCA mutation, suspected BRCA mutations or genemonic instability before treatment begins. In the phase III PAOLA clinical trial, patients receiving both drugs were 67% less likely to die or experience worsening of their cancers than patients who used only bevacizumab. Average progression-free survival (PFS) time was more than twice as long for women on the two-drug regimen, as well (37.2 months vs 17.7 months). The recommended Lynparza dose for its new indication is 300mg twice a day for up to two years. Treatment stops, however, if the cancer progresses or the patient can no longer stand drug side effects. Bevacizumab is available as the brand-name, Avastin® (bevacizumab – Genentech), and two biosimilars, MVASI (bevacizumab-awwb – Amgen) and Zirabev (bevacizumab-bvzr – Pfizer). Lynparza has a previous FDA indication as monotherapy for maintenance treatment of patients who have advanced cases of one of the three cancers that is in a full or partial response after first-line treatment with platinum-based chemotherapy (chemo). It also is approved for specific types of BRCA positive breast and pancreatic cancers.

Lynparzareceived another FDA approval on May 20, 2020, for treatment of adult patients who have deleterious or suspected germline or somatic homologous recombination repair (HRR) gene mutated metastatic castration-resistant prostate cancer (mCRPC). It should be used after the patient tries and fails Xtandi® - (enzalutamide - Pfizer/Astellas) or Zytiga® (abiraterone - Janssen). Lynparza was approved for prostate cancer based on results in the PROfound study, which found Lynparza reduced the risk of disease progression or death by 66% compared to Xtandi or Zytiga. The study evaluated HRR genetic mutation subpopulations, meaning that patients received Lynparza after positive results from appropriate diagnostic testing. Prostate cancer is fueled by testosterone, so patients should receive GnRH treatment or have both testicles surgically removed when starting the medication. Lynparza received FDA Breakthrough Therapy designation for the new indication. It also has FDA approvals for certain breast, ovarian and pancreatic cancers. The recommend dose of Lynparza for prostate cancer is 300mg taken orally twice daily with or without food. Click here for full prescribing information.

Pomalyst Approved for Kaposi Sarcoma

Pomalyst® (pomalidomide – Celgene/Bristol Myers Squibb) capsules was FDA approved on May 14, 2020, to treat adults who have Kaposi sarcoma (KS). Although it can be used whether or not the condition is related to AIDS, treatment with highly active antiretroviral therapy (HAART), which usually manages both AIDS and KS, will have to have stopped controlling KS before Pomalyst can be considered for patients living with AIDS. HAART still must be continued. Occurring mostly among patients who have immune-compromising disorders, KS is diagnosed for fewer than 2,000 individuals in the U.S. each year. It usually affects the skin, but it can attack the digestive system, lungs and other internal organs. The recommended dose of Pomalyst for KS is 5mg/day for the first 21 days of each 28-day cycle. Due to a boxed warning that it may cause severe damage or death for an unborn developing baby, women of childbearing age should be tested for pregnancy before being treated. They are advised to use two forms of reliable contraception during therapy. An additional boxed warning cautions about an increased risk of blood clots, heart attacks and strokes among patients taking Pomalyst. Its potential for serious side effects resulted in a risk evaluation and mitigation strategy (REMS) program that restricts its dispensing to limited quantities only through specifically certified prescribers and pharmacies. Originally approved in 2013, Pomalyst also is indicated to treat multiple myeloma. Look here for its revised prescribing information.

Qinlock Approved by FDA for Fourth-Line Gastrointestinal Stromal Tumors

On May 15, 2020, the FDA approved Deciphera Pharmaceuticals’ Qinlock (ripretinib) as a fourth-line kinase inhibitor for patients who have advanced gastrointestinal stromal tumors (GIST). Approximately 4,000 to 6,000 cases of GIST are diagnosed in the U.S. annually. The majority of cases are in people 50 years of age or older. About 80% of cases are driven by mutations in the tyrosine-protein (KIT)  and around 6% more are due to mutated platelet derived growth factor alpha (PDGFRα) genes. The approval was supported by positive data from INVICTUS, a phase III study of Qinlock compared to placebo for 129 patients who have advanced GIST and whose previous therapies included at least imatinib, Sutent® (sunitinib – Pfizer) and Stivarga® (regorafenib – Bayer). PFS was 6.3 months in Qinlock treated patients vs. one month for those receiving placebo; and the average overall survival (OS) was 15.1 months vs. 6.6 months, respectively. Patients should receive treatment with three or more kinase inhibitors, including imatinib (Gleevec® – Novartis, generics), prior to starting therapy with Qinlock. The recommended dosage is 150mg (three 50mg tablets) taken orally once per day. Patients should continue treatment until disease progression or unacceptable toxicity. Qinlock, available in 50mg oral tablets  launched in mid-May at an estimated annual WAC of $384,000. The FDA granted Qinlock Breakthrough Therapy, Fast Track designation, Orphan designation and Priority Review. The new drug application (NDA) was reviewed under the Real-Time Oncology Review (RTOR) pilot program and approval was also part of Project Orbis, a collaboration with Australian Therapeutic Goods Administration (TGA) and Health Canada. As a result, the FDA was able to approve Qinlock three months ahead of schedule. For full prescribing information see here.

Rubraca Approved for Prostate Cancer by FDA

On May 15, 2020, Clovis Oncology received FDA approval for Rubraca® (rucaparib) tablets for the treatment of adult patients with deleterious BRCA mutation mCRPC. Patients should be treated first with an androgen receptor therapy and a taxane-based chemo. Rubraca was the first PARP inhibitor approved for prostate cancer, a new indication for the medication which was previously approved for some ovarian, fallopian tube or primary peritoneal cancers. The recommended dose is 600mg orally (two 300mg tablets) twice per day with or without food until disease progression or unacceptable toxicity. Patients who are being treated for mCRPC should also receive a GnRH analog or have surgical removal of both testicles in order to lower testosterone production, a key driver of mCRPC. The approval was based on the clinical trial, TITON2, which showed a 44% objective response rate (ORR), or tumor shrinkage, measured by standard testing and assessed by blinded independent radiologic review (IRR). Furthermore, a 55% confirmed prostate specific antigen (PSA) response rate was detected in 115 patients with BRCA mutations. Rubraca received FDA Breakthrough Therapy designation for the new indication. It’s Accelerated Approval is contingent upon sustained results in the ongoing confirmatory TRITON3 trial. Go here for complete prescribing information.

New Indications for Opdivo-Yervoy Combination

Opdivo® (nivolumab) injection and Yervoy® (ipilimumab) injection, immune oncology agents made by Bristol Myers Squibb, received additional FDA indications on May 15, 2020 and May 26, 2020. The first new indication is for use, in combination, as an initial therapy to treat some adults who have metastatic NSCLC. Tumors must test positive for mutations in programmed death receptor-1 (PD-L1), but negative for genomic abnormalities in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) before treatment starts. For this NSCLC indication, recommended dosing is 3mg/kg of Opdivo given as a 30-minute IV infusion once every two weeks and 1mg/kg of Yervoy as a 30-minute IV infusion once every three weeks. After four doses, the Yervoy is discontinued, but the Opdivo lasts for as long as two years, provided that the cancer does not get worse and the patient can stand the drug’s side effects.

Awarded less than two weeks later, the second new approval, in combination with two cycles of platinum-doublet chemo, is for first-line treatment of adult patients who have metastatic or recurrent NSCLC with no EGFR or ALK genomic tumor aberrations. Tumors do not need PD-L1 expression and treatment is approved for both squamous and non-squamous NSCLC disease. Opdivo is a PD-1-blocking antibody that has indications for other cancers, including some types of melanoma, small cell lung cancer (SCLC), classic Hodgkin lymphoma and urothelial cancer. Yervoy, a monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4 (CTLA-4), has a stand-alone indication for melanoma. Used together, they treat specific kinds of renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC). For this type of metastatic NSCLC, the recommended dose of Opdivo is 360mg, infused over 30 minutes, once every three weeks; and Yervoy is given at 1mg/kg, over 30 minutes, once every six weeks along with two cycles of platinum-based doublet chemo once every three weeks. Singly and together, both drugs have several other indications for various types of cancer. Yervoy’s labeling carries a boxed warning that it can cause potentially life threatening immune-mediated adverse reactions involving any organ system. Patients should be tested for adrenal, hormone, liver, thyroid and other functions before Yervoy is initiated and before each dose. Both drugs are dispensed with patient Medication Guides due to serious side effects they may cause. Updated prescribing information is here for Opdivo, and here for Yervoy.

Tecentriq Receives Two New Indications

Genentech’s Tecentriq® (atezolizumab) injection was granted an additional FDA indication for treating NSCLC on May 18, 2020, and one for HCC on May 29, 2020. It is approved for first-line treatment of adults who have NSCLC tumors with 50% or more PD-L1 expression and no deformities in EGFR or ALK genes. For NSCLC, Genentech suggests a dose of 840mg once every two weeks, 1200mg once every three weeks or 1680mg once every four weeks, administered through an IV infusion. Additionally, in combination with bevacizumab (Avastin, MVASI or Zirabev), it is newly approved for first-line treatment of patients who have HCC that has spread or that cannot be removed by surgery. For HCC, both drugs will be administered by IV infusion starting with Tecentriq (at 1,200mg) and then bevacizumab (at 15mg/kg) on the first day of 21-day cycles. If bevacizumab’s side effects cause its discontinuation, Tecentriq still can be given at 840mg once every two weeks, 1,200mg once every three weeks or 1,680mg once every four weeks.  Because the HCC indication was granted under the Accelerated Approval review program using intermediate data from the phase III IMpower110 clinical trial, further clinical study confirmation of effectiveness and safety will be required before the FDA grants full approval. Either alone or in multi-drug regimens, Tecentriq has previous indications for some other kinds of NSCLC and for some small cell lung cancers (SCLC), triple-negative breast cancers (TNBC) and urothelial cancers. A Medication Guide outlining its possible side effects and other information should be provided at each dose. Here is current prescribing information for Tecentriq.

Kynmobi Approved for Parkinson’s Disease

On May 21, 2020, FDA approved Sunovion’s Kynmobi™ (apomorphine) to treat “off” episodes in patients who have Parkinson’s disease (PD). Approximately 950,000 Americans are estimated to have PD, with about 60,000 new cases annually. A progressive deterioration of nerve function due to reduced dopamine production, it can cause balance problems, shaking and stiffness. Although drugs that restore dopamine levels are used to treat PD, the drug effects sometimes “wear off” between doses. Kynmobi, a sublingually (SL) administered dopamine agonist, is designed to act quickly for relieving these “off” episodes. Recommended dosing is one film allowed to dissolve under the tongue as soon as an “off” episode begins. If needed, additional doses may be taken at intervals of at least two hours. Doses should be limited to a maximum of 30mg and no more than five doses should be administered per day. When starting therapy, the first dose should be given by a healthcare provider to determine the correct strength for each patient and to watch for side effects. Before the first dose and for at least a few months after beginning treatment, patients need to take medications to help prevent the nausea and vomiting that the drug may cause. According to the manufacturer, Sunovion, Kynmobi SL film will launch in September in strengths of 10mg, 15mg, 20mg, 25mg, and 30mg. For its prescribing information, please look here.

New Type of Contraceptive, Phexxi, Approved

Evofem Biosciences received FDA approval on May 22, 2020, for Phexxi (L-lactic acid/citric acid/potassium bitartrate) vaginal gel. A unique form of contraception, Phexxi (formerly called Amphora) is a non-hormonal product that works by adjusting the pH (acid-alkaline balance) in the vagina to an acidic level that does not sustain sperm. It also provides vaginal lubrication. One prefilled, single-dose applicator (five grams) is inserted vaginally up to one hour before having sex. In phase III clinical trials, Phexxi prevented around 86% of unplanned pregnancies. Marketing is scheduled for early September at a WAC estimated at $250 to $275 for a box of 12 applicators. If Phexxi is covered by the Affordable Care Act (ACA), it will be available for no copayment, but Evofem is still negotiating for ACA coverage. Phexxi’s prescribing information can be found here.

FDA approves Alunbrig as First-Line Treatment Option

Takeda Oncology’s Alunbrig (brigatinib) received an additional approval from the FDA on May 22, 2020. An oral TKI, Alunbrig gained approval as a first-line treatment for patients who have metastatic ALK+ NSCLC as detected by an FDA-approved test. Only about 2% to 8% of NSCLC patients also have ALK mutations. For ALK+ patients whose cancer returns after initial treatment, approximately 70% have metastases in their brains. Originally approved for patients who have progressed or who were intolerant to Xalkori® (crizotinib – Pfizer/EMD Serono), Alunbrig was superior to Xalkori in results from the phase III ALTA 1L trial. In the trial, patients who have locally advanced or metastatic ALK+  NSCLC, without prior ALK-inhibitor treatment, were assigned either to Alunbrig dosed at 90mg once per day for seven days and then increased to 180mg once per day or to Xalkori 250mg twice per day. At two years of follow-up, assessment by a blinded independent review committee (BIRC) found that Alunbrig reduced the risk for disease progression or death with a 24-month median PFS vs 11 months for Xalkori. Compared to the Xalkori group, patients taking Alunbrig saw a confirmed ORR of 74% vs 62% and a confirmed intracranial ORR with brain metastases at baseline of 78% vs 26% for patients taking Xalkori. For full prescribing information see here.

Dupixent Approved for Children

On May 26, 2020, the FDA approved Dupixent® (dupilumab – Sanofi) for children six to 11 years of age who have moderate to severe atopic dermatitis and whose disease is not adequately controlled with topical prescription therapies. It can be used when topical therapies are not advisable, as well. Dupixent, the first biologic approved for this patient population, blocks interleukin-4 (IL-4) and interluekin-13 (IL-13) receptors – key drivers of the inflammatory process. Dupixent will be given as SC injections, at different injection sites. The pediatric weight-based dose, for patients up to 11 years of age is 300mg once every four weeks for children weighing between 15kg (33 pounds) and 30kg (66 pounds) or 200mg once every two weeks for children weighing between 30kg and 60kg (132 pounds) following an initial loading dose. The FDA approved Dupixent under Priority Review and Breakthrough Therapy designations based on phase III clinical trial results that demonstrated children treated with Dupixent and topical corticosteroids (TCS) showed improvement at 16 weeks vs TCS alone.  Independent assessment found that 30% to 39% of patients receiving Dupixent achieved clear to almost clear skin vs 10% to 13% of those on TCS alone. Dupixent also is approved to be used with other asthma medicines for maintenance treatment of moderate-to-severe eosinophilic or oral-steroid dependent asthma in patients 12 years and older, and as an add-on maintenance therapy for adult patients who have uncontrolled chronic rhino-sinusitis with nasal polyps (CRSwNP). See here for full prescribing information. 

FDA Approves VESIcare LS for Pediatric Patients

The FDA approved Astellas’ VESIcare LS® (solifenacin) oral suspension, a new dosage form, on May 27, 2020, for treatment of pediatric patients who have neurogenic detrusor over-activity (NDO). A form of bladder dysfunction, NDO is caused by disease or injury in the nervous system. If left untreated it can put pressure on the bladder, possibly leading to damage in the kidneys and upper urinary track. In addition, spontaneous bladder muscle contractions can lead to unexpected and frequent leakage of urine with symptoms of urgency. VESIcare LS helps increase the amount of urine the bladder can hold and decrease the amount of urine that leaks. Its effectiveness for children was established in two trials that included patients two years to 17 years old. The primary endpoint was the maximum amount of urine the bladder could hold after 24 weeks of treatment. In the first study, patients could hold an average of 39mL (about one ounce and one-third) more urine than when they began; and in the second, they could hold 57mL (nearly two ounces) more. VESIcare 5mg/5mL oral solution will be available in the U.S. in late 2020. Recommended doses, which are based on the patient’s weight, should be taken once daily followed by liquid, such as milk or water. For full prescribing information check here.

FDA Approves Artesunate to Treat Severe Malaria

Artesunate for Injection, a component of the natural product artemisinin, was approved by the FDA on May 27, 2020. An Orphan Drug previously available to Americans only through the Centers for Disease Control and Prevention’s (CDC) investigational new drug (IND) program, it is indicated as the drug of choice to treat severe cases of malaria. The manufacturer, Amivas US, estimates that about 15% of the approximately 2,000 U.S. patients who are diagnosed as having malaria each year will have the severe form of the disease. Severe malaria, defined as 5% or more of malaria parasites in the blood, can cause sudden and potentially fatal blood clotting, breathing, kidney and central nervous system (CNS) effects. The recommended dose of Artesunate is 2.4mg/kg. Patients receive three doses given as one-to-two-minute bolus IV injections at 12-hour intervals on the first day followed by one dose daily until parasite levels are 1% or lower, but no longer than seven total days. Because it does not treat all the stages of malaria, treatment with artesunate should be accompanied by therapy with another malaria drug, such as primaquine, that is approved for malaria caused by certain types of parasites. A complete, three-day course of treatment with an oral antimalarial drug, such as Coartem® (artemether/lumefantrine - Novartis), should be taken after artesunate treatment ends. Dispensed in single-dose vials containing 110mg of powder for reconstitution, Artesunate will continue to be available on an IND basis as its production increases to commercial levels and the distribution network is established over the next few months. Look here for its prescribing information.

Pediatric Indication and New Formulation for Sirturo

Under the FDA’s Accelerated Approval and Priority Review pathways, Janssen gained pediatric approval on May 27, 2020, for Sirturo® (bedaquiline) tablets. It also was granted approval for a 20mg tablet that can be crushed and mixed with liquids or soft foods for patients who have trouble swallowing whole tablets. Used along with other drugs to treat tuberculosis (TB), Sirturo now is indicated for children as young as five years old, who weigh at least 15kg and who have TB that has resisted therapy with previous drug regimens. The recommended dose for children weighing between 15kg and 30kg is 200mg once every day for two weeks and then 100mg three times a week for 22 additional weeks. Children who weigh more than 30kg, adolescents and adults are advised to take 400mg once daily for the first two weeks followed by 200mg three times a week to total 24 weeks of therapy. At least three other TB drugs must be taken at the same time, as well. Because strict adherence to medication is essential to curing TB, all doses of all drugs being taken should be monitored visually to assure they actually were taken appropriately. The full 24-week course of treatment must be completed, as well. A boxed warning on the label for Sirturo cautions that the risk of death was about 10% higher among patients who took it in clinical trials than among patients who took an inactive tablet. In addition, it may disturb heart rhythm, so electrocardiograms should be done before Sirturo treatment starts, after 12 weeks and at 24 weeks. Patients who have certain conditions or who take some other drugs that could cause arrhythmias should be tested more often. Electrolytes and liver enzymes also should be checked before beginning treatment. Launch and pricing information for the 20mg tablets are not yet available. Revised prescribing information may be found here.

MedWatch Update

Extended-Release Metformin

The FDA released a notice on May 28, 2020, about unacceptable amounts of a probable cancer-causing chemical, N-Nitrosodimethylamine (NDMA), in some tablets of extended-release metformin. Not all manufacturers are affected and no immediate-release tablets are believed to contain excess NDMA. Although short-term ingestion of NDMA in the small amounts found in the tested tablets is not likely to cause cancer, repeated exposure over very long periods may increase the risk, slightly. The FDA is asking all manufacturers to test each lot of their products, let the FDA know if NDMA levels are high and keep lots with unacceptable levels off the market. Some already distributed lots have been recalled by several manufacturers. Patients who are concerned about their extended-release metformin should continue to take it and discuss an alternative product with their healthcare providers. More information is available in the FDA’s press release.

FDA Approves Zilxi to Treat Rosacea

A new formulation, Zilxi (minocycline – Foamix, a subsidiary of Menlo Therapeutics) topical foam, 1.5%, was FDA approved on May 28, 2020. An antibiotic, it is the first minocycline approved to treat adults who have acne-like inflammatory lesions from rosacea. It will be dispensed in 30gm canisters with directions for once daily application to affected areas of the face. It should be rubbed in gently at about the same time every day — at least one hour before bathing, going to bed, showering or swimming. Because the propellant used in Zilxi is flammable, patients should not use it near an open flame. They should avoid smoking while applying it and for several minutes after application. Oral antibiotics in the same class as Zilxi may cause sensitivity to sunlight. Even though the risk is less with minocycline topical products, patients still should protect against sunburn from natural or artificial light, such as in tanning beds. A launch is planned by the fourth quarter of 2020, but pricing is not yet available. Prescribing information is here.

Brilinta Given New Indication

The FDA awarded a new indication to AstraZeneca’s antiplatelet drug, Brilinta® (ticagrelor) tablets, on May 28, 2020. Taken at 60mg twice a day along with a single 100mg or lower-dose aspirin, it now is approved to decrease the risk of an initial major CV event, such as a heart attack, a stroke or death, for patients who have coronary artery disease (CAD) that puts them at high risk for a CV event. Patients in the clinical trial leading to the approval all were at least 55 years old and they also had diabetes, but the new indication is not restricted only to older patients or to patients who have both conditions. In the study, the risk of a CV event was reduced by about 10% for patients taking Brilinta and aspirin compared to participants taking aspirin and a placebo. For its original FDA approval in 2011, Brilinta is taken at 90mg twice a day for one year and then 60mg daily as CV event prevention for patients who have acute coronary syndrome (ACS), who have had a previous heart attack or who may be at risk for blood clots after a coronary stent has been placed. The labeling for Brilinta contains a boxed warning that using it may raise the risk of excessive bleeding and that discontinuing treatment may cause a CV event to be more likely. The warning also indicates that maintenance doses of aspirin above 100mg/day should be avoided because they may reduce the effectiveness of Brilinta. Here is full prescribing information.

Oriahnn Receives FDA Approval

Oriahnn (elagolix/estradiol/norethindrone and elagolix) capsules was approved by the FDA on May 29, 2020. It is the first oral drug indicated to reduce heavy menstrual bleeds for women who have uterine fibroids and who have not yet reached menopause. Non-cancerous tumors of the uterus that are worsened by monthly hormone variations, fibroids affect over one-half of women by the time they reach 50 years of age. They are more common among overweight women, those nearing menopause, women who have never given birth and those who have a family history of the condition. Although many women have few or no symptoms, about one-quarter of women who have fibroids experience serious effects such as severe pain that can interfere with usual activities and excessive bleeding that can cause anemia. The only cure for fibroids is hysterectomy. Oriahnn combines elagolix, a GnRH inhibitor that blocks natural production of estrogen and progesterone, while its estradiol and norethindrone components block receptors for naturally produced hormones. Patients will take one capsule containing all three ingredients once each morning and one capsule of just elagolix every evening. A boxed warning and Medication Guide cautions that all estrogen/progestin products may raise the risk of blood clots; particularly for women who smoke, who have uncontrolled hypertension or who are 35 years of age or older. With its partner, Neurocrine Biosciences, Oriahnn’s manufacturer, AbbVie, plans a launch by the end of June. It will be dispensed in cartons of four blister-packed cards each containing a seven-day supply of the capsules. Pricing is not immediately available. For its full prescribing information, look here.

Expanded Indication for Taltz

Taltz® (ixekizumab – Eli Lilly and Company) injection was granted an additional indication on May 29, 2020. An interleukin-17 (IL-17) inhibitor that blocks inflammation, it now is indicated for treating non-radiographic axial spondyloarthritis (nr-xSpA). The Spondylitis Association of America estimates that about 2.7 million Americans have axial spondyloarthritis (axSpA), an inflammatory arthritis of the spine that usually is diagnosed in the late teens to mid-forties for patients who have chronic, severe back pain. Up to 35% of those patients have nr-axSpA, which does not show in x-rays, making it difficult to recognize. All forms of axSpA are painful and progressive. Ultimately, the spine can become twisted and/or fused. To treat nr-axSpA, Taltz will be given by SC injection once every four weeks at a dose of 80mg. Originally approved by the FDA in 2016 to treat adults who have psoriasis, it later was given additional indications, including for pediatric psoriasis. Check here for Taltz’s updated prescribing information.

New Cyramza Indication

Also on May 29, 2020, Lilly’s Cyramza® (ramucirumab) injection was FDA approved as first-line treatment for metastatic NSCLC that has deletions in EGFR exon 19 or mutations in EGFR exon 21. An estimated 15% of the approximately 230,000 individuals diagnosed with NSCLC in the U.S. each year have mutations in EGFR. An inhibitor of new blood vessel formation, Cyramza will be used along with erlotinib (Tarceva® - Genentech/Astellas, generics) tablets, which block EGFR tyrosine kinase. In the phase III RELAY clinical study, PFS was seven months longer for patients treated with the two-drug combination than for patients receiving erlotinib and a placebo (19.4 months vs 12.4 months). For the new indication, the recommended Cyramza dose is 10mg/kg, given by a 30-minute IV infusion, once every two weeks. Patients will be verified as having EGFR mutations through diagnostic testing before treatment begins. Cyramza has previous indications for certain colorectal, liver and stomach cancers, as well as for NSCLC in combination with docetaxel. Treatment continues until the cancer advances or the patient cannot stand therapy side effects. For revised prescribing information, please look here.


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