Entadfi Earns FDA Approval

Entadfi™, a combination of finasteride 5mg and tadalafil 5mg, was approved by the U.S. Food and Drug Administration (FDA) on Dec. 9, 2021. It is indicated for treating urinary symptoms, such as more frequent urination, dribbling urine and increased nighttime urination, which result from benign prostatic hyperplasia (BPH). Patients will take one capsule at about the same time each day for as long as 26 weeks. The manufacturer, Veru, plans to begin marketing Entadfi early in 2022 through GoodRx^® and also through its own telepharmacy/telemedicine program. Pricing is not yet available. 

FDA Approves Tarpeyo

The FDA granted Accelerated Approval for Tarpeyo™ (budesonide) delayed-release capsules on Dec. 15, 2021. A new version of a corticosteroid that is used widely in multiple dose forms for a number of allergic and inflammatory conditions, it is the first FDA-approved drug for treating adult patients who have primary Immunoglobulin A nephropathy (IgAN) and whose condition is likely to deteriorate quickly. Many patients who have IgAN eventually enter end-stage kidney disease, which often needs dialysis and/or a kidney transplant. Formerly called Nefecon, Tarpeyo decreases the amounts of protein lost in urine by regulating antibodies that cause IgAN. Treatment with it is recommended to start at a urine protein-to-creatinine ratio of 1.5gm/gm or higher. Patients swallow four whole capsules (16mg) one hour or more before any food once every morning for eight and one-half months. For the next two weeks, doses are reduced to two capsules (8mg) per day and then treatment is ended. In the continuing phase III clinical study that led to the approval, urine protein decreased by an average of 34% for patients treated with Tarpeyo added to the current standard of care, a renin-angiotensin-system inhibitor (RASi), as opposed to an average 5% reduction for patients using only RASi. Calliditas Therapeutics is prepared to launch Tarpeyo in the first quarter of 2022, but its cost and distribution plans have not been made public. Confirmation of the drug’s effectiveness, including how it impacts kidney function, will be needed before the FDA gives it full approval.

Orencia Approved to Prevent Graft-vs-Host Disease

Initially FDA approved in 2005 to treat rheumatoid arthritis (RA), Orencia^® (abatacept – Bristol Myers Squibb) now is indicated for use along with methotrexate and a calcineurin inhibitor, such as Prograf^® (tacrolimus – Astellas), to prevent acute graft-versus-host disease (aGVHD) for certain patients. The combination will be used for individuals who are at least two years old and who are receiving a hematopoietic stem cell transplant (HSCT) from a donor who is not a family member of the recipient and whose human leukocyte antigen (HLA) profile either duplicates the recipient’s or is off by only one allele, a gene variant. GVHD happens when T-cells in the donated stem cells attack the recipient’s tissues and organs. It can be acute, typically appearing between about 14 and 100 days after the procedure, or chronic, emerging beyond the 100-day mark. It causes potentially serious gastrointestinal (GI) disturbances, liver damage and skin rashes. As many as 70% of patients who have had an HSCT are estimated to develop aGVHD. Most cases are not severe and most can be resolved by standard treatment with a corticosteroid and immunosuppressants. However, some patients who have aGVHD progress to the chronic form of the condition and others are diagnosed with cGVHD long after the transplant. Until the Orencia regimen was approved on Dec. 15, 2021, no standard preventive therapy was approved in the U.S. for aGVHD, but several drugs, including Imbruvica^® (ibrutinib), Jakafi^® (ruxolitinib) and Rezurock^™ (belumosudil), that are indicated to treat GVHD, are used off-label to prevent it, as well. A T-cell co-stimulation modulator that also is approved for treat psoriatic arthritis ( ) and polyarticular juvenile idiopathic arthritis (pJIA), Orencia decreases T-cell activation. To prevent aGVHD, Orencia will be given as a series of four 60-minute intravenous (IV) infusions – one on the day before the transplant and then one each on the fifth, fourteenth and twenty-eighth days afterward. The dose for patients who are six years old and older is 10mg/kg (up to 1,000mg); for younger patients, the first infusion is at 15mg/kg, followed by 12mg/kg for the remaining three treatments. Orencia should not be used at the same time as the patient is using another immunosuppressant, a biologic disease-modifying antirheumatic drug (bDMARD) or a Janus-associated kinase (JAK) inhibitor. See its current prescribing information here.

FDA Approves Rinvoq to Treat Psoriatic Arthritis

AbbVie gained an additional FDA approval on Dec. 14, 2021, for its JAK inhibitor Rinvoq^® (upadacitinib) extended-release tablets. It now is indicated for treating certain patients who have PsA. At a dose of one tablet (15mg) daily, it is approved for adults who have PsA that has not responded to one or more tumor necrosis factor (TNF) inhibitors or who cannot use a TNF blocker. Rinvoq should not be taken at the same time as biologic DMARDs, immunosuppressants or other JAK inhibitors are being used. It carries the same boxed warning that the FDA requires for all JAK inhibitors, including Rinvoq, that treat inflammatory conditions. Patients taking them have a higher chance of dying, developing certain cancers, suffering cardiovasvular (CV) events, having blood clots and acquiring severe infections. Patients taking one of them also should be screened for tuberculosis (TB) before starting treatment and periodically while therapy continues. Rinvoq originally was FDA approved in August 2019 for the treatment of adults who have moderately to severely active RA that is not managed with methotrexate, or who cannot tolerate methotrexate treatment. Check here for its complete prescribing information. 

New Xeljanz Indication

Also on Dec. 14, 2021, another JAK inhibitor, Xeljanz^®/Xeljanz^® XR (tofacitinib/tofacitinib extended-release – Pfizer) tablets/oral solution, was granted FDA approval to treat ankylosing spondylitis (AS). It will be reserved for second-line or later therapy after at least one TNF inhibitor fails to manage AS. An inflammatory condition that causes pain and inflexibility mainly in the back and hip joints, AS is estimated to affect around 350,000 American patients — with most diagnosed by age 30. To treat it, the recommended dose of Xeljanz is 5mg two times a day; for Xeljanz XR the recommendation is 11mg one time daily. Xeljanz/XR also is indicated to treat some patients who have RA, PsA, pJIA and ulcerative colitis (UC). The FDA-mandated boxed warning outlines the increased risks of blood clots, cancer, adverse cardiovascular (CV) events and serious infections that may be associated with the use of any JAK inhibitor that is taken to treat an inflammatory disorder. TB tests should be performed before starting therapy and frequently during treatment. For its fully revised prescribing information, look here.

Pediatric Indication Approved for Zepatier

The indication for Zepatier^® (elbasvir 50mg/grazoprevir 100mg – Merck) tablets was broadened on Dec. 9, 2021. In addition to adults, it now includes patients who are between the ages of 12 years and 18 years and who weigh 30kg (66 pounds) or more. The combination of a non-structural protein 5A (NS5A) inhibitor and a non-structural protein 3 and 4A (NS3/4A) protease inhibitor, one tablet is taken daily for 12 weeks to treat genotypes 1 and 4 of the hepatitis C virus (HCV). Some patients may need 16 weeks of therapy and some may need to take ribavirin, as well as Zepatier. A boxed warning on the label warns that using or stopping direct-acting antiviral drugs, such as Zepatier, could cause a resurgence of hepatitis B (HBV) for patients infected with both viruses, even if HBV has been cleared, previously. Liver failure and death are possible outcomes, if HBV is not controlled. Here is updated prescribing information.

Apretude Approved for Preventing HIV

ViiV Healthcare’s Apretude (cabotegravir extended-release injectable suspension) received approval from the U.S. Food and Drug Administration (FDA) on Dec. 20, 2021. It is indicated as pre-exposure prophylaxis (PrEP) for teens and adults who weigh 35kg (77 pounds) or more and who are at increased risk of being infected with HIV-1. Before beginning Apretude, some patients may be prescribed a one-month-long course of Vocabria, an oral form of cabotegravir that was FDA approved in January 2021, to be sure they can tolerate the drug. For preventing HIV-1 infection, one 600mg dose of Apretude is injected intramuscularly (IM) by a healthcare professional once every two months after the first two injections are administered one month apart. Patients must test negative for HIV-1 before every injection. Labeling for Apretude has a boxed warning that using it while infected with HIV-1 has led to drug-resistant variations of the virus. ViiV plans to launch Apretude early in 2022 at a wholesale acquisition cost (WAC) of $3,700 per dose. Distribution plans are unknown at this time. For complete prescribing information, look here. 

At a Glance

• Brand (Generic) Name: Apretude (cabotegravir extended-release injectable suspension)
• Manufacturer: ViiV Healthcare
• Date Approved: Dec. 20, 2021
• Indication: as PrEP to reduce the risk of sexually acquired HIV-1 infection for at-risk adults and adolescents weighing at least 35kg
• Dosage Forms Available: 600mg single-dose vials for intramuscular injection
• Launch Date: early 2022
• Estimated Annual Cost: WAC of $22,200 after $25,900 for the first year
• More than one million Americans live with HIV and about 34,000 more are diagnosed with it annually, as estimated by the Centers for Disease Control and Prevention (CDC). 
• According to CDC calculations, only about one-quarter of around 1.2 million Americans who are eligible for HIV-1 PrEP actually have prescriptions for it.
• Apretude is the first injectable, long-term agent for PrEP. An HIV-1 integrase strand transfer inhibitor (INSTI), it obstructs the entry of viral DNA into human T-cells.
• In two clinical studies comparing Apretude to oral PrEP with Truvada® (emtricitabine/tenofovir disoproxil fumarate – Gilead), the risk of HIV-1 infection was 69% lower for transgender women who have sex with men and for men whose gender matches their birth sex. For women who identify as women the chances were 90% lower.
• Adverse effects from Apretude were generally mild to moderate and temporary. They included back pain, fatigue, headache, irritation at the injection site and rash.
• Until Apretude’s approval, only two oral drugs were FDA indicated to provide PrEP to help prevent infection from HIV-1. Studies have shown that adherence to once-daily oral regimens tends to decline over time, especially among adolescents.

Updated DrugWatch Document Available

The Emerging Therapeutics department has updated DrugWatch, a document that highlights near-term pipeline drugs as well as potential new generic opportunities. The DrugWatch document is attached. 

Tezspire® (tezepelumab-ekko – AstraZeneca/Amgen) injection was approved by the United States Food and Drug Administration (FDA) on Dec. 17, 2021. A thymic stromal lymphopoietin (TSLP) blocker, it is a fully human monoclonal antibody used for add-on maintenance therapy for adult or pediatric patients 12 years of age and older who have severe asthma. Its use is not limited to a specific subtype of asthma. A healthcare provider should administer Tezspire subcutaneously (SC) at a dose of 210mg once every four weeks. However, it is not indicated for acute severe asthma symptoms. The launch is planned for the middle of January 2022 with pricing to be disclosed at that time. It will be available through a large network of specialty pharmacies that includes Accredo. Here is the complete prescribing information for Tezspire. 

At a Glance

• Brand (Generic) Name: Tezspire (tezepelumab-ekko) injection
• Manufacturer: AstraZeneca and Amgen
• Date Approved: Dec. 17, 2021
• Indication: for add-on maintenance treatment of adult and pediatric patients aged 12 years and older who have severe asthma
• Dosage Form Available: single-dose vials and single-dose pre-filled syringes containing 210mg per 1.91mL of Tezspire for subcutaneous injection
• Launch Date: middle of January 2022
• Estimated Annual Cost: Not yet available 
• In the U.S., nearly 25 million people suffer from asthma with 5% to 10% having severe asthma. Approximately 5.1 million U.S. children under the age of 18 years old have asthma — making it the most common chronic health condition in children.
• Asthma is considered severe if the treatment requires medium-to-high doses of inhaled corticosteroids in combination with different long-acting treatments or if asthma remains uncontrolled even with correct use and adherence to medication. 
• Allergens, dust, viruses and other irritants may prompt the production of TSLP, an early pro-inflammatory cytokine that then triggers immune cells to release inflammatory substances. High levels of TSLP seem to correlate with more severe asthma. Many patients who have severe asthma also have high levels of biomarkers, such as immunoglobulin E (IgE) and/or eosinophils (a type of white blood cell) in their blood.
• In the clinical trials that led to its approval, Tezspire or placebo was added to standard treatments such as inhaled corticosteroids, other asthma controllers and even oral corticosteroids for patients with severe, unmanaged asthma. Patients with eosinophil levels of 300 cells/microliter or more treated with Tezspire showed a 77% reduction in annualized asthma exacerbation rates (AAER) and an 85% drop in hospitalizations. Tezspire-treated patients also reported better asthma control, lung function and health-related quality of life (QoL).
• The drug was approved using Priority Review and it was designated a Breakthrough Therapy.

NewsFlash – Vyvgart Approved to Treat Myasthenia Gravis

The U.S. Food and Drug Administration (FDA) approved Vyvgart™ (efgartigimod alfa-fcab) injection, the first in a new class called neonatal Fc receptor (FcRn) blockers, on Dec. 17, 2021. It is indicated to treat adults who have generalized myasthenia gravis (gMG) that tests positive for anti-acetylcholine receptor (AChR) antibodies, which typically belong to the immunoglobulin G (IgG) type. Acetylcholine is a naturally produced chemical essential to convey nerve impulses to muscles. MG is a rare autoimmune condition that makes skeletal muscles weaker and more easily tired than normal. Vyvgart is infused intravenously (IV) once weekly in four weekly cycles with subsequent cycles separated by at least 50 days based on clinical evaluation. The recommended dose is 10mg/kg with an upper limit of 1,200mg/dose. The manufacturer, argenx, plans a quick launch through a small network of specialty pharmacies that includes Accredo. Pricing information has not yet been announced. Prescribing information is here. 

At a Glance

• Brand (Generic) Name: Vyvgart (efgartigimod alfa-fcab)
• Manufacturer: argenx
• Date Approved: Dec. 17, 2021
• Indication: to treat adults who have gMG that has AChR antibodies
• Dosage Forms Available: single-dose 400mg/20mL vials for dilution and IV infusion
• Launch Date: Soon after FDA approval
• Estimated Annual Cost: Not yet available
• Caused by an autoimmune reaction that damages parts of muscles where nerve signals are received, gMG results in muscle weakness. The eyes and face particularly are affected for most patients, and around one patient in 10 may have potentially fatal involvement of muscles used to breathe.
• Estimated to affect up to 40 patients in 100,000 population, about 65,000 Americans have MG. It is more common among women than men. Women usually are diagnosed with the condition in early adulthood, but cases in men usually are discovered after the age of 40 years.
• Approximately 85% of patients who have MG also have AChR antibodies of the IgG type.
• By sticking to FcRn, Vyvgart helps to decrease the amounts of IgG in the blood. As a result, blood levels of AChR increase — allowing more normal nerve-to-muscle functioning.
• Among the phase III clinical study participants who received Vyvgart, 44 (67.7%) had at least a two-point improvement on the MG Activities of Daily Living (MG-ADL) scale, as compared to 27.7% of the patients who got placebo infusions. 
• The types and percentages of adverse effects among the two study groups were similar. They include infections of the respiratory and urinary tracts and headaches.
• Current pharmacological treatment for gMG depends mainly on an oral cholinesterase inhibitor, pyridostigmine, which helps to maintain acetylcholine levels. Typically dosed as 10 60mg capsules taken throughout the day, as many as 25 capsules per day may be needed to manage severe MG. Other drugs may include chemotherapy (chemo) and steroids.
• Alexion’s Soliris® (eculizumab), an infused complement inhibitor, was approved in 2017 for the treatment of adults who have gMG who are AChR-antibody positive. Soliris costs around $650,000 per year.
• Surgical removal of the thymus gland helps some patients and plasma exchange may be used in severe cases. Other treatment is supportive or aimed at controlling symptoms.
• Designated as an Orphan Drug, Vyvgart was approved under the FDA’s Fast Track program.