New Indication for Dupixent

On May 20, 2022, two months before the FDA’s Priority Review action date, Dupixent® (dupilumab) was FDA approved for an additional indication. The first medication approved to treat eosinophilic esophagitis (EoE), it also is the first gastrointestinal (GI) disease indication for Dupixent. Its new indication is for patients 12 years and older, weighing at minimum 40kg (88 pounds). EoE is a chronic immune disease that destroys the esophagus and impairs swallowing function due to inflammation. Presently, corticosteroids and proton pump inhibitors are used off-label, along with diet, to reduce symptoms of swelling and improve the ability to swallow. Regeneron estimates that 160,000 people are actively being treated for EoE in the United States, with roughly one-third still symptomatic after numerous therapies. Developed by Regeneron and Sanofi, Dupixent is an interleukin-4 alpha receptor (IL-4Rα) blocking antibody that disrupts the inflammatory process. Available in single dose prefilled syringes and pen devices, it is administered subcutaneously (SC) either at home by patients or caregivers or in a healthcare setting by a professional. In the two-part Phase 3 trial that evaluated It for treating EoE, Dupixent 300mg weekly demonstrated significantly improved signs and symptoms of EoE compared to the placebo after 24 weeks. Among the patients receiving Dupixent, symptoms decreased by 64% or 69% compared to 32% or 41% among the patients using a placebo. The Dysphagia Symptom Questionnaire, a patient-reported measure of swallowing difficulty, improved by as much as 23.8 points in Dupixent-treated patients versus as little as 9.6 points for those receiving placebo. Injection site reaction, upper respiratory tract infection (URI) and arthralgia were the most common adverse effects associated with using Dupixent. It also is approved for treating atopic dermatitis and certain types of asthma in patients six years old and older, and to treat adults who have chronic rhinosinusitis with nasal polyposis.

New Vidaza Indication

Through the U.S. Food and Drug Administration’s (FDA) Priority Review program, Vidaza® (azacitidine), a hypomethylating agent manufactured by Celgene Corporation, was approved for a new indication on May 20, 2022. With a Breakthrough Therapy designation, it now is indicated for pediatric patients aged one month and older who have newly diagnosed juvenile myelomonocytic leukemia (JMML). Typically diagnosed in children before the age of four, JMML affects up to 3% of the 4,000 American children who are diagnosed with leukemia annually. A rare cancer of the blood, it previously had no FDA approved treatment other than a stem cell transplant, which is successful for around 50% of all cases. In an open-label clinical trial for the new indication, 18 patients who have JMML were evaluated for a confirmed clinical response that was sustained for at least four weeks. Nine of the patients had a complete (cCR) or partial (cPR) remission as defined by the international JMML response criteria, which are standard measures of disease progression. The median time to response was 1.2 months. The most common side effects were fever, rash, upper respiratory tract infection and anemia. For patients one month to less than one year of age or weighing less than 10kg (22 pounds), the recommended dose is 2.5mg/kg. For patients aged one and older and weighing 10kg or more, the recommended dose is 75mg/m2. The recommended duration of treatment is between three and six 28-day cycles with Vidaza given by intravenous (IV) infusion on the first seven days. In the trial, 17 of the patients went on to receive a stem cell transplant. Vidaza is not interchangeable with oral azacitidine. It originally was approved to treat adults for several subtypes of myelodysplastic syndrome (MDS), a rare type of bone marrow cancer.

Tibsovo Indication Extended

The FDA expanded the indication for Sevier Pharmaceuticals’ isocitrate dehydrogenase-1 (IDH1) inhibitor, Tibsovo® (ivosidenib) tablets, on May 25, 2022. Initially FDA approved in July 2018 for treating adults who have relapsed or refractory acute myeloid leukemia (r/rAML) that has been confirmed as having IDH1 mutations, Tibsovo later was approved to treat IDH1-mutated cholangiocarcinoma (cancer in the bile ducts). Along with Vidaza given as an IV or SC injection, Tibsovo now is approved as initial treatment for new cases of IDH1-positive AML in patients who are at least 75 years old or who cannot tolerate induction doses of chemotherapy (chemo) due to having other medical conditions. Dosing for all its indications is 500mg (two tablets) every day. In the clinical study that led to the new approval, 47.0% of patients receiving Tibsovo and Vidaza had complete remissions and their average overall survival (OS) lasted 24.0 months versus 15.0% and 7.9 months for those using Vidaza and a placebo tablet. Vidaza was administered at a dose of 75mg/m2 once a day on either the first seven days or days one through five, eight and nine in 28-day cycles. The combination therapy should be given for at least six cycles, provided that the patient can stand the drugs’ side effects and the cancer does not worsen. A boxed warning cautions that differentiation syndrome, a potentially fatal condition that involves very rapid production of immature myeloid cells, may be associated with taking Tibsovo. Its new indication was approved under FDA Priority Review and Real-Time Oncology Review.

New Dosage Form for Tyvaso

A dry powder inhaler formulation, Tyvaso DPI™ (treprostinil) inhalation powder, was FDA approved on May 23, 2022. It is the first DPI that is indicated to improve exercise capability for patients who have WHO Group 1 pulmonary arterial hypertension (PAH) and patients who have WHO Group 3 pulmonary hypertension associated with interstitial lung disease (PH-ILD). PAH is estimated to affect about 45,000 Americans; and around 30,000 patients in the U.S. have PH-ILD. Originally FDA approved in 2009 for delivery through a specialized inhalation device, Tyvaso is a prostacyclin analog. It works by widening blood vessels in the lungs and body. As one side effect, patients using either form of it may have low blood pressure. Because it also interferes with the normal activity of blood platelets, some patients may experience excess bleeding. The recommended starting dose for the DPI form is one 16mcg cartridge inhaled four times a day, approximately four hours apart. With increases of 16mcg per dose every one to two weeks, the recommended maintenance dose is 48mcg or 64mcg four times a day. United Therapeutics plans to introduce Tyvaso DPI early in June. It will be dispensed in packages containing 16mcg, 32mcg, 48mcg or 64mcg cartridges and up to five inhalation devices, which each can be used for only one week.

New Biosimilar Approved for Neulasta

Amneal Pharmaceuticals received FDA approval on May 26, 2022, for Fylnetra™ (pegfilgrastim-pbbk), a biosimilar to Amgen’s Neulasta®. It is indicated to decrease the risk of infections for patients who receive cancer drugs that interfere with the bone marrow’s production of blood cells and that are associated with a clinically significant incidence of febrile neutropenia, an adverse effect of some chemo. Although multiple variables are involved in developing febrile neutropenia, approximately 60,000 patients develop it annually during treatment, with patients who have blood cancers more likely to be affected. 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. Fylnetra’s recommended dose is 6mg (one prefilled syringe) as an SC injection at least two weeks before or one day after the first chemo treatment in each cycle. Along with the brand product, other biosimilars — Fulphila® (pegfilgrastim-jmdb – Mylan/Biocon), Nyvepria™ (pegfilgrastim-apgf – Pfizer), Udenyca® (pegfilgrastim-cbqv – Coherus BioSciences) and Ziextenzo® (pegfilgrastim-bmez – Sandoz) — already are available in the U.S. None of the biosimilars is interchangeable with Neulasta or with each other, however. Amneal has not released its pricing or launch plans.

Generics Available for Alimta

Several companies, including Accord Healthcare, Dr. Reddy’s Laboratories, Eugia Pharma and Zydus Lifesciences, have been FDA approved for generic versions of Alimta® (pemetrexed – Eli Lilly). Some already have started supplying pemetrexed in the United States. It can be used alone or in combination with other oncology drugs to treat malignant pleural mesothelioma (MPM) and some types of non-small cell lung cancer (NSCLC). A folate analog metabolic inhibitor, it is given as IV injections at a dose of 500mg/m2 on the first day of each 21-day treatment cycle. Because it may disrupt the activity of bone marrow, patients receiving pemetrexed need supplementation with folic acid and vitamin B12. IQVIA estimated U.S. sales at $1.2 billion for the 12-month period that ended on March 31, 2022.

Recalls

Strides Losartan

On May 18, 2022, Strides Pharma recalled lots that expire in May 2022 or after for all three strengths of its losartan tablets. The angiotensin receptor blocker (ARB), which is used mainly to treat high blood pressure, was recalled due to containing unacceptably high amounts of an azide impurity. Although the FDA typically considers similar recalls to be at Class II level, we are treating Strides’ losartan recall as Class I (to the consumer level). In a Safety Hazard Evaluation, Strides estimated a moderate risk to patients.

Teva Anagrelide

Teva Pharmaceuticals elevated a recall for one lot of anagrelide capsules, 0.5mg, to the consumer level on May 20, 2022. In routine testing, some capsules from the affected lot did not dissolve as well as expected. Inadequate doses of anagrelide, an antiplatelet agent, could raise the risk of blood clots, excess bleeding or cardiovascular (CV) events, such as heart attacks and strokes. The FDA’s notice has more information.

Vtama® (tapinarof)

Dermavant Sciences was awarded U.S. Food and Drug Administration (FDA) approval on May 23, 2022, for its psoriasis treatment, Vtama® (tapinarof) Cream, 1%. It is the first in a new class, aryl hydrocarbon receptor (AhR) agonists, which work differently than topical corticosteroids, a current cornerstone of psoriasis treatment. Indicated for use by adults, it is applied sparingly once a day to affected skin, including sensitive areas such as the armpits, face and external genitals. It should not be used in the eyes, mouth or internal genitals, however. Unlike steroids, which should be used only for short periods, Vtama has no limits on how long it can be applied. It will be packaged in 60gm tubes that have a wholesale acquisition cost (WAC) of $1,325 each. Launch is planned for early in June 2022.

At a Glance

• Brand (Generic) Name: Vtama (tapinarof) Cream, 1%.
• Manufacturer: Dermavant Sciences, a unit of Roivant Sciences
• Date Approved: May 23, 2022
• Indication: to treat adults who have plaque psoriasis
• Dosage Forms Available: 60gm tubes
• Launch Date: June 2022
• Estimated Annual Cost: WAC for each tube is $1,325. Total cost depends on how many tubes are needed to control psoriasis and how long each episode of active treatment lasts.
• Psoriasis is an autoimmune disease that involves excessive activity of the immune system that causes skin cells to grow much faster than normal. As a result, cells build up on the skin’s surface as large, raised spots (plaques). In addition to itchy, painful, red skin, patients who have psoriasis also may experience internal organ damage due to inflammation.
• An estimated 7.5 million Americans who are at least 20 years old have some degree of psoriasis. It is slightly more common among Caucasians than among other ethnic groups and it affects about equal numbers of men and women.
• Vtama interferes with the inflammatory effects of interleukin-17 (IL-17) to help restore more normal skin cell turnover.
• In two phase III clinical trials, 35% to 40% of patients who used Vtama for as long as 12 weeks achieved clear or nearly clear skin as opposed to about 6% of those who used the cream base without any active ingredient in it.
• Side effects for 5% or more of study patients using Vtama included dermatitis, infections of the hair follicles on the skin and infections of the nose and/or throat.
• Presently, topical treatment for psoriasis depends mainly on various strength corticosteroid products and forms of vitamin D. Other topical treatments may include anthralin, coal tar and vitamin A.