FDA Update: December 2018

Dec 27, 2018

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

New Pill Bottle

New Opioid, Dsuvia, Approved

On Nov. 2, 2018, AcelRx Pharmaceuticals was given U.S. Food and Drug Administration (FDA) approval for Dsuvia (sufentanil sublingual tablets, 30mcg), C-II. For use only in certified healthcare facilities, it is indicated for treating adults who have intense, acute pain that requires an opioid. It will be available in the first quarter of 2019 as prefilled, single–tablet dispensers that a health professional will use to insert one tablet under the patient’s tongue. Doses must be separated by at least one hour and no more than 12 tablets should be given in any 24-hour period. In clinical studies, Dsuvia began to work within 15 minutes. Compared to 65% of study patients given a placebo, only 22% of Dsuvia-treated participants needed rescue treatment with morphine within the first 12 hours after abdominal surgery. A Risk Evaluation and Mitigation Strategy (REMS) limits distribution to certified heath care facilities. Boxed warnings on its label caution that opioids can cause potentially severe breathing problems, that they can be life-threatening if swallowed by children and that neonatal withdrawal syndrome is possible for babies born to women who used opioids while pregnant. Prescribing information for Dsuvia is available here.

FDA Approval for Sympazan to Treat Lennox-Gastaut Syndrome

The FDA approved Sympazan(clobazam) oral film on Nov. 2, 2018. Made by Aquestive Therapeutics, it is a new dosage form of clobazam that is indicated in combination with other anti-seizure drugs to treat patients at least two years old who have Lennox-Gastaut syndrome (LGS). A rare form of epilepsy, LGS is believed to affect fewer than 20,000 patients in the U.S. It is difficult to treat because it causes multiple different types of seizures, some lasting for several minutes and/or repeating rapidly. Multi-drug therapy generally is required throughout the patient’s life. With a planned launch in November, Sympazan will be available in foil pouches each containing one 5mg, 10mg or 20mg berry-flavored film. Recommended daily dosing is 5mg to 20mg per day for children weighing 30kg (66 pounds) or less and 10mg to 40mg for children heavier than 30kg. Doses of 10mg or more should be divided into two equal parts. Clobazam also is available as Aquestive’s brand, Onfi® and generics for both oral tablets and oral suspension. Labeling for all clobazam products carries a boxed warning that taking it at the same time as an opioid could result in extreme sleepiness, breathing problems, coma or even death. They are C-IV controlled substances. Full prescribing information for Sympazan may be found here.

Udenyca Biosimilar to Neulasta Approved

Udenyca (pegfilgrastim-cbqv – Coherus BioSciences) a biosimilar to Amgen’s Neulasta®, was FDA approved on Nov. 2, 2018. A leukocyte growth factor, it reduces the risk of infection for patients who have non-myeloid malignancies being treated with anti-cancer drugs that are associated with bone marrow suppression and clinically significant febrile neutropenia. As an adverse effect of some chemotherapy (chemo), the drugs that kill cancer cells also destroy normal cells, including neutrophils – white blood cells that protect against infections. As a result, infections are more likely and usually more serious among cancer patients receiving chemo. Pegfilgrastim is a PEGylated form of the granulocyte colony-stimulating factor (G-CSF) analog filgrastim, giving it a longer duration of action. G-CSF causes cells in bone marrow to produce more neutrophils. The approval of Udenyca follows that of Fulphila (pegfilgrastim-jmdb – Mylan/Biocon), which the FDA approved on June 4, 2018. Neither biosimilar is interchangeable with Neulasta. Coherus plans to launch Udenyca on Jan. 3, 2019. According to IQVIA, U.S. annual sales of Neulasta were approximately $4.3 billion in 2017. For prescribing information, please see here.

Lorbrena Approved to Treat Metastatic Non-Small Cell Lung Cancer

The FDA approved Lorbrena® (lorlatinib - Pfizer) on Nov. 2, 2018. It is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), which will be used to treat patients who have ALK-positive metastatic non-small cell lung cancer (NSCLC) that has worsened despite treatment with Xalkori® (crizotinib - Pfizer) and at least one other ALK inhibitor for metastatic disease. It also is indicated for NSCLC that was treated with Alecensa® (alectinib - Genentech) or Zykadia® (ceritinib - Novartis) as the first ALK inhibitor therapy for metastatic disease. Recommended dosing is one 100mg tablet per day, but doses may be decreased to 50mg or 75mg/day if the patient has serious side effects from the drug. Pfizer has not yet released a launch date. Complete prescribing information is located: here.

Ortho Dermatologics Gains Approval for Bryhali

Bryhali (halobetasol propionate) Lotion, 0.01%, received FDA approval on Nov. 6, 2018, for the treatment of adults who have plaque psoriasis. A widely used high-potency corticosteroid, halobetasol is available in a number of other topical dosage forms, some as generics. Bryhali uses a proprietary lotion formula, however; that allows it to be used for up to eight weeks as compared with a two-to-four week limit for most other high-potency steroids. Ortho Dermatologics, a division of Bausch Health, planned to launch Bryhali in November. It will be marketed in 60Gm and 100Gm tubes with directions to apply a thin layer to the affected areas once a day. Full prescribing information may be found here.

Empliciti Approved for Multiple Myeloma

The FDA approved a new indication for Bristol-Myers Squibb’s Empliciti® (elotuzumab) on Nov. 6, 2018. It now can be used, along with Pomalyst® (pomalidomide – Celgene) and dexamethasone, to treat adults who have multiple myeloma that has relapsed or become resistant after two or more previous treatments with Revlimid® (lenalidomide – Celgene) and a proteasome inhibitor, such as Velcade® (bortezomib – Millennium/Takeda) or Kyprolis® (carfilzomib – Amgen). Empliciti is an antibody that activates the immune system and also seeks out a specific protein on myeloma cells. In the clinical study that led to the approval, 53.3% of patients treated with all three drugs responded to therapy compared to 26.3% of patients receiving only Pomalyst and dexamethasone. Additionally, progression-free survival (PFS) averaged 10.3 months for patients using all three drugs versus about 4.7 months for Pomalyst/dexamethasone-treated participants. For its new indication, Empliciti will be infused intravenously (IV) once a week for two 28-day cycles, and then once every four weeks. Dosing is weight based at 10mg/kg for the first eight infusions and at 20mg/kg thereafter. Its revised, complete prescribing information is available here.

Yupelri Approved for COPD

On Nov. 9, 2018, the FDA approved Theravance Biopharma and Mylan’s Yupelri (revefenacin) inhalation solution. It is a long-acting muscarinic antagonist (LAMA) nebulization solution for the once-daily maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Yupelri, which can be used with a standard jet nebulizer, will be available as single-dose vials containing 175mcg/3mL of solution. Pricing and availability information is not yet known. Full prescribing information can be found here.

Hepatocellular Carcinoma Indication Approved for Keytruda

Merck’s Keytruda® (pembrolizumab) received accelerated approval from the FDA for an additional indication on Nov. 9, 2018. It now is approved to treat patients who have hepatocellular carcinoma (HCC) that has previously been treated with Nexavar® (sorafenib). Keytruda is a human programmed death receptor-1 (PD-1)-blocking antibody that helps the body’s immune system attack cancer cells. It originally was FDA approved on Sep. 4, 2014, for the second- or third-line treatment of patients with unresectable or metastatic melanoma. Since then, it has received multiple new indications for treating various cancer types. In May 2017, Keytruda became the first drug approved for treating colorectal cancer and any solid tumors that are microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) regardless of the tumors’ primary site of origin. For its HCC indication, Keytruda will be infused once every three weeks at a dose of 200mg. Continued approval of Keytruda for HCC is contingent upon confirmatory trials that demonstrate a clinical benefit for patients. Revised prescribing information can be found here.

U.S. Launch for Retacrit

Pfizer released Retacrit (epoetin alfa-epbx), its biosimilar for Epogen® (Amgen) and Procrit® (Johnson & Johnson), to the U.S. market on Nov. 12, 2018. Retacrit is approved for treating anemia caused by chronic kidney disease, chemotherapy or the use of zidovudine in patients with HIV infection. It is also approved to reduce the chance that a red blood cell transfusion will be needed in patients undergoing elective, noncardiac, nonvascular surgery. Its dose depends on the indication. Although its indications are the same as those for Epogen and Procrit, Retacrit is not interchangeable with either. All epoetin products have a boxed warning about increased risks of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access and tumor progression or recurrence with their use. Retacrit will be introduced at a list price approximately two-thirds of Epogen’s and less than one-half of Procrit’s. According to IQVIA, combined annual sales of Epogen and Procrit were approximately $2.4 billion in 2017. Full prescribing information for Retacrit is located here.

Aemcolo Approved to Treat Traveler’s Diarrhea

Aries Pharmaceuticals was granted approval by the FDA on Nov. 16, 2018, for Aemcolo (rifamycin) delayed-release tablets, 194mg. Aemcolo is an antibiotic that is indicated for adults who have travelers’ diarrhea due to noninvasive bacteria – primarily Escherichia coli (E. coli). It has been formulated with a proprietary technology to prevent drug release until the tablets are in the colon, so it has very little systemic effect. Recommended dosing is two tablets twice each day for three days. Aries plans to launch Aemcolo in the first quarter of 2019. Approval was given under the FDA’s Fast Track program. It also received Qualified Infectious Disease Product (QIDP) status, which extends its exclusivity through 2028. Its prescribing information is here.

Temixys Approved to Treat HIV

On Nov. 16, 2018, Celltrion received approval from the FDA for Temixys (lamivudine 300mg /tenofovir disoproxil fumarate 300mg) tablets.  A combination of two nucleoside reverse transcriptase inhibitors, it will be taken once a day along with other HIV drugs to treat HIV-1 infection for patients weighing at least 35kg (about 77 pounds). Its labeling includes a boxed warning that discontinuing the use of lamivudine or tenofovir disoproxil fumarate can activate hepatitis B virus (HBV) for patients who have or who have had HBV. Patients should be monitored for signs of HBV before, during and for several months after treatment with Temixys. Celltrion plans to launch Temixys early in 2019. Prescribing information is available here.

Gamifant Approved to Treat Primary Hemophagocytic Lymphohistiocytosis

Gamifant® (emapalumab-lzsg) was approved by the FDA on Nov. 20, 2018, to treat an extremely rare hereditary condition, primary hemophagocytic lymphohistiocytosis (HLH). It is an antibody that inhibits interferon gamma, which is overproduced by patients who have HLH. It will be administered by (IV at a starting dose of 1mg/kg per day every three or four days. Doses may be increased over the first few treatments to a maximum of 10mg/kg if symptoms and lab values do not improve on smaller doses. Patients will continue receiving Gamifant along with dexamethasone, until the patient undergoes a stem cell transplant or treatment with the drug is no longer tolerable. Cost information is not yet available. The manufacturer, Swedish Orphan Biovitrum (Sobi), expects to begin shipping Gamifant to treatment centers in the first quarter of 2019. Complete prescribing information can be found here.

Daurismo Approved for Acute Myeloid Leukemia

On Nov. 21, 2018, the FDA approved Pfizer’s Daurismo (glasdegib) for the first-line treatment of acute myeloid leukemia (AML) in adult patients who are 75 years or older or who have comorbidities that preclude use of intensive induction chemotherapy. The National Cancer Institute estimates that approximately 19,500 patients are diagnosed with AML each year in the United States. Almost half of adults who have AML cannot be treated with intensive chemotherapy due to its toxicities. Daurismo is a hedgehog pathway inhibitor; blocking this pathway may impede cancer stem cell development and survival. It is used in combination with low-dose cytarabine (LDAC), a type of chemotherapy. The recommended dose of Daurismo is 100mg orally, once daily. Launch was expected in early December. Full prescribing information is located here.

Indication Extended for Venclexta

AbbVie/Genentech’s Venclexta ® (venetoclax) tablets received an FDA indication on Nov. 21, 2018, for treating adults who have newly-diagnosed AML, but who cannot undergo intense chemotherapy. Eligible patients include those age 75 years and older and those who have previous or co-existing conditions that make effective treatment difficult for them to tolerate. Venclexta inhibits B-cell lymphoma-2 (BCL-2), a protein that may interfere with apoptosis (the self-destruction process) in cancer cells. For its new indication, Venclexta will be used along with azacitidine, decitabine or low-dose cytarabine. Dosing is initiated at 100mg on the first day, 200mg on the second and 400mg on the third. Based on which additional agent is being used, maintenance dosing is either 400mg/day or 600mg/day until AML worsens or the patient can longer continue therapy. Complete revised prescribing information is available here.

Vitrakvi Approved for Solid Tumors with NTRK Gene Fusions

The FDA approved Vitrakvi® (larotrectinib – Loxo Oncology) capsules and oral solution on Nov. 26, 2018. A kinase inhibitor, Vitrakvi is the first drug FDA indicated to treat solid tumors that have neurotrophic receptor tyrosine kinase (NTRK) gene fusions. Although rare, NTRK fusions are found in many malignancies including some cancers of the appendix, breast, colon, lungs, pancreas or thyroid. Vitrakvi is “site agnostic”, meaning that it can be used for many different solid tumors, regardless of their site of origin, as long as they have the NTRK abnormality. Dosing is based on body surface area, but most patients will take 100mg twice a day. Loxo Oncology and Bayer will be co-marketing Vitrakvi. Its complete prescribing information can be found here.

Truxima, Biosimilar to Rituxan, Approved

On Nov. 28, 2018, the FDA) approved Celltrion and Teva’s Truxima® (rituximab-abbs), the first biosimilar to Genentech’s Rituxan®. Truxima is indicated for use alone or in combination with chemotherapy to treat adult patients with CD20-positive, B-Cell non-Hodgkin’s lymphoma (NHL). Rituximab is an infused monoclonal antibody that targets CD20 receptors on cancerous and normal B-cells resulting in their destruction. Truxima is not interchangeable with Rituxan. However, the two products have no clinically significant differences in safety, purity or effectiveness. Due to patent protection, Truxima was only approved for three NHL indications. Rituxan is also approved to treat chronic lymphocytic leukemia, rheumatoid arthritis, Wegener’s granulomatosis, microscopic polyangiitis and pemphigus vulgaris. Celltrion and Teva have yet to release pricing information and a launch date for Truxima. Complete prescribing information for Truxima is available here.

Xospata Approved for Acute Myeloid Leukemia

The FDA approved Astellas Pharma’s Xospata® (gilteritinib) on Nov. 28, 2018, for the treatment of adults who have relapsed or refractory AML) with a FLT3 mutation as detected by an FDA-approved test. Approximately 25% to 30% of patients with AML have a mutation in the FLT3 gene. These mutations are associated with worse outcomes. The recommended dose of Xospata, an oral kinase inhibitor, is 120mg once daily. It will be supplied as 40mg tablets soon after its approval. Full prescribing information can be found here.

Firdapse Approved for Lambert-Eaton Myasthenic Syndrome

Catalyst Pharmaceuticals received approval from the FDA on Nov. 28, 2018, for Firdapse® (amifampridine) tablets to treat adults who have Lambert-Eaton myasthenic syndrome (LEMS). A rare autoimmune disease, LEMS interrupts the flow of nerve impulses to muscles. Firdapse blocks potassium channels to keep calcium channels open longer, which enhances nerve signal transmission. The recommended initial dose is 15mg to 30mg daily divided into three or four parts. Doses may be increased by 5mg per day every few days to a maximum of 80mg per day, with no more than 20mg taken in any single dose. Complete prescribing information is located here.

EpiPen Generics Available 

After an August FDA approval, limited quantities of Teva’s generic to EpiPen® 0.3mg epinephrine auto-injectors were released on the U.S. market in late November 2018. Epinephrine  auto-injectors, in both 0.3mg and 0.15mg strengths, are used for the emergency treatment of allergic reactions, including anaphylaxis. They are handheld devices that deliver exact amounts of epinephrine using a spring-loaded needle through intramuscular (IM) or subcutaneous (SC) injection when pressed firmly against the outside of the upper thigh. Manufacturing interruptions, recalls and increased demand have resulted in frequent shortages of epinephrine auto-injectors over the last few years. Teva’s product will help to increase supply. However, it was introduced at $300 for a package of two injectors, which is the same wholesale acquisition cost (WAC) as for Mylan’s AG. Two other auto-injectors, Impax Laboratories’ AG to Adrenaclick® (epinephrine injection, USP, auto-injectors) and Auvi-Q® (epinephrine injection - Kaléo), also are available in the U.S. Symjepi, a prefilled syringe version of self-injected epinephrine, may be launched soon and Teva plans to introduce a 0.15mg strength generic auto-injector, as well.

Authorized Generics Planned for Epclusa and Harvoni

Asegua Therapeutics, a subsidiary of Gilead Sciences, plans to introduce AGs for Gilead’s hepatitis C drugs, Epclusa® (sofosbuvir/velpatasvir) and Harvoni® (ledipasvir/sofosbuvir) in January 2019. Epclusa is approved to treat adults who have any of the six genotypes of the hepatitis C virus (HCV); Harvoni can be used to treat several types of HCV for patients as young as 12 years old. List cost for the most common course of treatment will be $24,000 for either drug, which is what Gilead estimates is comparable to the brand’s costs after rebates and discounts.

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