March 4, 2022
New Biosimilar for Neupogen
Amneal Pharmaceuticals received FDA approval for Releuko™ (filgrastim-ayow) on Feb. 25, 2022. A biosimilar for Amgen’s Neupogen®, it is a colony-stimulating factor (CSF) that promotes the production of neutrophils, a key component of the immune system. Releuko’s indications are to decrease infection risk for patients who are undergoing myelosuppressive chemotherapy (chemo) for non-myeloid cancer, to accelerate neutrophil recovery for patients receiving induction or consolidation chemo for acute myeloid leukemia (AML), to shorten the length of neutropenia for patients having bone marrow transplants and to mitigate their conditions for patients who have congenital, cyclic or idiopathic neutropenia. Doses, which differ according to the condition being treated, may be injected intravenously (IV) or subcutaneously (SC). It will be available in single-dose vials containing either 300mcg/0.5mL or 480mcg/08mL. Its launch is planned for the third quarter of 2022. Two other Neupogen biosimilars, Zarxio™ (filgrastim-sndz – Sandoz), which was released to the U.S. market in September 2015 and Nivestym™ (filgrastim-aafi – Pfizer), introduced in October 2018, are available in the U.S. For 2021, IQVIA estimates that U.S. sales for all filgrastim products amounted to $407 million, which includes $275 million for biosimilars.
Norliqva Receives FDA Approval
A new formulation of the calcium channel blocker amlodipine, Norliqva® oral solution (CMP Pharma) was FDA approved on Feb. 24, 2022. It works by relaxing smooth muscles to dilate blood vessels, which lowers blood pressure for patients at least six years old and to treat coronary artery disease (CAD) in any age group. Recommended dosing for adults is 5mg to 10mg once each day; for children and small, or elderly adults, 2.5mg to 5mg once a day. It will be dispensed in 150mL bottles that contain 1mg/mL of peppermint-flavored solution. Amlodipine also is available as oral tablets (Norvasc®/generics) and oral suspension (Katerzia®). Pricing and launch plans have not been announced for Norliqva.
Kaléo Approved for Naloxone Auto-Injector
Under the FDA’s Fast-Track process and in cooperation with the Department of Defense’s Joint Project Manager for Chemical, Biological, Radiological, and Nuclear Medical unit, Kaléo has been given FDA approval for a high-dose (10mg/0.4mL) naloxone auto-injector. Designated as a Rapid Opioid Counter-measure System, it was approved on Feb. 28, 2022, for emergency use by members of the military and responders to chemical incidents. It can treat patients who are at least 12 years old and who are known or believed to have been exposed to fentanyl or another high-strength opioid that has been used as a chemical weapon. It also can be used to prevent breathing and neurologic side effects for emergency workers or armed forces who must enter spaces that are known or believed to be contaminated by high-strength opioids. For treatment, one dose should be injected intramuscularly (IM) or SC as soon as possible after exposure and before emergency medical help is called. If needed, additional doses can be given until first responders arrive. To prevent adverse respiratory and central nervous system (CNS) effects of opioids, one dose is delivered before entering the contaminated area; more doses may be needed if exposure is prolonged. Kaléo’s Naloxone Auto-Injector, 10mg, which will be packaged in cartons of 10 individual single-dose injectors, will not be distributed through civilian pharmacies. Prescribing information is here.
FDA Approves First Medicated Contact Lenses
Acuvue® Theravision™ with Ketotifen (etafilcon A drug-eluting contact lens with ketotifen) was FDA approved on March 2, 2022. Each lens contains 19mcg of ketotifen, an antihistamine that is widely used in over-the-counter eye drops to manage the itching associated with allergic conjunctivitis. Usually, contact lenses have to be removed before eye drops can be used, and not reinserted for 10 to 15 minutes for most eye drops. The new drug-containing lenses are indicated to prevent ocular itch due to allergic conjunctivitis and to provide vision correction for patients who do not have red eyes, who are suitable for contact lenses and who do not have more than 1.00 D of astigmatism. Because ketotifen is incorporated into the contact lenses, separate eye drops are no longer needed while the lenses are in place. In clinical trials, allergy relief began within three minutes for some participants and lasted for as long as 12 hours. Although the anti-itching effect may diminish, the lenses still can be worn for longer than 12 hours to correct vision. The lenses are intended to be used for one day, only, though; they never should be cleaned or re-used. They should be removed if the eyes become reddened or irritated, if vision changes significantly or if the wearer produces unusually high amounts of tears. They should not be worn while sleeping or when engaging in activities that would result in the lenses getting wet. A representative of the manufacturer, Johnson & Johnson Vision Care, verified that they will be distributed by ophthalmologists, optometrists and vision clinics; not through pharmacies. They will be dispensed in boxes of 30 separately blister-packed lenses. A launch date and pricing are not yet available. For full prescribing information, look here and for patient instructions, here.
Carvykti™ (ciltacabtagene autoleucel)
Was approved by the U.S. Food and Drug Administration (FDA) on Feb. 28, 2022. A chimeric antigen receptor T-cell (CAR-T) drug, it contains antibodies for B-cell maturation antigen (BCMA), which are prevalent on multiple myeloma cells. It will be used for adult patients after treatment with at least four previous multiple myeloma regimens and given as a single intravenous (IV) infusion by specially trained providers in authorized healthcare facilities. T-cells are extracted from the patient’s blood, genetically modified to identify and eliminate cells that express BCMA and then duplicated to very high amounts in a laboratory to create Carvykti. The resulting product is frozen and shipped back to the healthcare facility for reinfusion into the patient. Carvykti has a boxed warning and a risk evaluation and mitigation strategy (REMS) because using it may be associated with potentially fatal side effects. Janssen and Legend Biotech USA are marketing Carvykti jointly in the U.S. Initially, it will be launched to a small group of certified treatment centers and then to a larger number of facilities as the ability to produce it increases. Its wholesale acquisition cost (WAC) is $465,000. Complete prescribing information is here.
At a Glance
- Brand (Generic) Name: Carvykti™ (ciltacabtagene autoleucel)
- Manufacturer: Janssen/Legend
- Date Approved: Feb. 28, 2022
- Indication: for the treatment of adult patients who have relapsed or refractory multiple myeloma after four or more prior lines of therapy, including with a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody
- Dosage Forms Available: patient-specific cell suspensions of approximately 0.5-1.0×106 CAR-positive viable T cells per kg of body weight, with a maximum dose of 1×108 CAR-positive viable T cells per single-dose IV infusion
- Launch Date: Immediately
- Estimated Annual Cost: a one-time WAC of $465,000
- Multiple myeloma, a blood cancer that affects bone marrow plasma cells, causes deficiencies in red blood cells, platelets and white blood cells. It can cause fragile bones, kidney damage, elevated blood calcium levels and a higher risk of infections.
- The American Cancer Society (ACS) estimates that approximately 35,000 new patients will be diagnosed with multiple myeloma annually. Although only about one-half of patients survive for five years beyond their diagnosis, around 130,000 Americans are living with some stage of the disease.
- Carvykti sticks to and destroys cells that secrete BCMA, a protein that is common on multiple myeloma cells.
- It will be used following treatment failure from four or more prior treatments that include a proteasome inhibitor, such as bortezomib; an immunomodulatory agent, such as Revlimid® (lenalidomide); and an anti-CD38 monoclonal antibody, such as Darzalex® (daratumumab).
- The numerous other drugs available to treat multiple myeloma include several chemo regimens and some targeted therapies. High doses of chemo followed by stem cell transplants also are used for patients who can tolerate them. Resistance eventually develops to most pharmaceutical therapies, however; and many patients suffer relapses.
- In the CARTITUDE-1 clinical trial, 95 of the 97 patients eligible for final evaluation had an overall response (OR) to treatment, with 76 participants having a complete response. The average response lasted 21.8 months.
- Due to instances of cytokine release syndrome (CRS), Parkinsonism, Guillain-Barré syndrome, recurring cytopenia, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) and immune effector cell-associated neurotoxicity syndrome (ICANS) among study patients, Carvykti has boxed warnings on its labeling and a Risk Evaluation and Mitigation Strategy (REMS). Other serious side effects may include febrile neutropenia, fever, low blood pressure and pneumonia.
- Abecma® (idecabtagene vicleucel – Bristol Myers Squibb/bluebird bio) is another BCMA-directed CAR-T cell therapy that was approved in March 2021 for treating multiple myeloma. Other CAR-T cell therapies approved for different cancers include Breyanzi® (lisocabtagene maraleucel), Kymriah® (tisagenlecleucel), Tecartus™ (brexucabtagene autoleucel) and Yescarta® (idecabtagene vicleucel)
- Carvykti has the FDA’s Orphan Drug and Breakthrough Therapy designations.
BioPharma’s Vonjo™ (pacritinib)
The U.S. Food and Drug Administration (FDA) granted Accelerated Approval to CTI BioPharma’s Vonjo™ (pacritinib) capsules on Feb. 28, 2022. By inhibiting specific enzymes – particularly Janus-associated kinase 2 (JAK2), interleukin 1 receptor-associated kinase 1 (IRAK1) and FMS-like tyrosine kinase 3 (FLT3) – it treats certain adult patients who have myelofibrosis. It is indicated for patients who have either intermediate or high-risk primary or secondary myelofibrosis and who have severely low platelet counts (less than 50×109/L). Recommended dosing is 200mg (two capsules) two times a day. Vonjo is expected to be marketed in the U.S. within around 10 days at a wholesale acquisition cost (WAC) of about $19,500 per month. Here is its prescribing information.
At a Glance
- Brand (Generic) Name: Vonjo (pacritinib)
- Manufacturer: CTI BioPharma
- Date Approved: Feb. 28, 2022
- Indication: to treat adults who have intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis and a platelet count below 50×109/L
- Dosage Forms Available: 100mg capsules
- Launch Date: within 10 days
- Estimated Annual Cost: approximately $234,000
- Myelofibrosis is an uncommon form of blood cancer resulting from over activity of the signaling pathways controlled by JAKs. Mutations in blood-forming stem cells cause a high production of atypical blood cells that overwhelm normal blood cells and cause fibrosis within bone marrow. Most patients are diagnosed in their 50s or after. Estimated survival is 3.5 years to 11 years, on average.
- With as many as 21,000 patients in the United States diagnosed, myelofibrosis usually occurs spontaneously (primary), but 10% to 15% of cases have other causes (secondary).
- Primary cases usually have no apparent triggers, but about one-half of patients test positive for mutations in the JAK2 gene. Roughly one-fifth of patients who have primary myelofibrosis eventually develop acute myelogenous leukemia (AML).
- Secondary myelofibrosis typically follows another blood condition, such as polycythemia vera or essential thrombocytopenia.
- Because bone marrow cannot produce enough normal blood cells, the spleen and liver begin to generate blood cells, which usually causes the organs to enlarge. Symptoms include anemia, fatigue, fever, night sweats and pain below the left ribs.
- Vonjo blocks the actions of JAK2, IRAK1 and additional enzymes to decrease abnormal blood cell formation due to aberrant JAK signaling.
- In the PERSIST-2 clinical trial, 107 patients took 200mg of Vonjo twice daily and 100 patients continued on their previous best available therapies. After 24 weeks, spleen volume, a standard measure of treatment effectiveness, decreased by an average of one-third or more for 29% of the patients taking Vonjo as compared to only 3% of those using their standard therapies.
- At least one-fifth of Vonjo-treated patients in the study experienced anemia, diarrhea nausea or peripheral edema. Fewer than 3% of study participants developed more serious adverse effects that included heart failure, hemorrhaging and pneumonia.
- Two other oral JAK inhibitors, Jakafi® (ruxolitinib – Incyte) tablets and Inrebic® (fedratinib – Bristol Myers Squibb) capsules are FDA approved to treat myelofibrosis. However, they are not indicated for treating patients whose platelet counts are severely low.
- Because Vonjo was given Accelerated Approval, positive results from continuing clinical trials are needed for full FDA approval. It also received a Priority Review.