Vivjoa Approved for Chronic Yeast Infections

On April 28, 2022, the U.S. Food and Drug Administration approved Mycovia Pharmaceuticals’ Vivjoa™ (oteseconazole capsules) to reduce the frequency of recurring vulvovaginal candidiasis (RVVC) in females who have a history of RVVC. Since Vivjoa can cause harm to a fetus, it is recommended only for females who do not have reproductive potential, such as biological females who are post-menopausal or who have another form of permanent infertility. According to the Centers for Disease Control and Prevention (CDC), RVVC is defined as three or more occurrences of acute symptomatic vulvovaginal yeast infections within 12 months. It’s estimated that 75% of adult women will have one yeast infection in their lifetime and around 50% of them will have a recurrence. Of those women who have a recurrence, approximately 9% will develop RVVC. Symptoms of RVVC include itching, burning, irritation and inflammation of the vulvovaginal area. Vivjoa is a tetrazole-pyridine hybrid, fungal-specific inhibitor of cytochrome P51 (CYP51), which is essential for the stability fungal cell walls. Vivjoa will be available as 150mg oral capsules that should be taken with food. Dosing for Vivjoa comes in two regimens. Vivjoa-only therapy consists of 600mg on day one, 450mg on day two and starting on day 14, 150mg once every seven days for 11 weeks. Alternatively, Vivjoa can be prescribed along with a separate prescription of fluconazole 150mg taken on days one, four and seven; followed by Vivjoa 150mg daily on days 14 through 20; then 150mg of Vivjoa once every seven days beginning on day 28 and lasting from weeks four through 14. Launch for the drug is expected in the second quarter of 2022.

Epsolay Approved to Treat Rosacea

A new formulation of benzoyl peroxide, Epsolay® cream, 5%, was approved by FDA on April 22, 2022. Using a proprietary microencapsulated silica delivery system, it is indicated for the treatment of adults who have rosacea, a common chronic skin condition that causes acne, dryness, inflammation, and redness. Typically diagnosed for patients who are in their 30s and older, rosacea is more common among women – especially those with light complexions. To treat it, Epsolay should be applied once each day to control inflammatory outbreaks. In clinical trials that included approximately 550 patients, nearly 50% of those using Epsolay reported clear or nearly clear skin after 12 weeks of therapy. Fewer than 30% of participants who applied the cream base without active medication had similar results. Some patients in both groups experienced irritated, itchy or swollen skin. Because benzoyl peroxide may increase sensitivity to sunlight, individuals who use any product that includes it should limit sun exposure and use appropriate sunscreens. Although several other topical treatments are FDA approved for treating rosacea, Epsolay is the first benzoyl peroxide specifically indicated for it. Developed by the Israeli company, Sol-Gel Technologies, Epsolay will be marketed in the United States by Galderma. A launch date and price have not been released.

Ultomiris Gains New indication

AstraZeneca’s Alexion Rare Disease division was granted a new FDA indication on April 27, 2022, for Ultomiris® (ravulizumab-cwvz) injection. The long-acting C5 complement inhibitor now is approved to treat generalized myasthenia gravis (gMG) for adult patients who test positive for anti-acetylcholine receptor (AChR) antibodies. Doses are based on the patient’s weight and they are given as intravenous (IV) infusions. After an initial loading dose, the recommended dose for gMG is infused once every eight weeks. With an estimated prevalence of fewer than 100,000 patients in the United States, gMG is a progressive autoimmune condition that causes muscle weakness and fatigue. Typically, it is diagnosed for women who are in their 20s or 30s, but not until much later (60s or 70s) for men. About four-fifths of gMG patients have AChR antibodies. Originally approved in December 2018, for the treatment of adults who have the rare condition, paroxysmal nocturnal hemoglobinuria (PNH), Ultomiris also is indicated to treat another rare disease, atypical hemolytic uremic syndrome (aHUS). Both prior indications are now extended for patients as young as one month old. Its labeling includes a Boxed Warning that highlights an increased risk of serious meningococcal infections when using it. Patents should be vaccinated with a meningococcal vaccine at least two weeks prior to receiving their first dose. During therapy, patients also should be monitored for early signs of meningococcal infections. Ultomiris is available only through a limited program under a Risk Evaluation Mitigation Strategy (REMS). Prescribers must enroll in the program and patients are required to receive a Medication Guide that describes the risks associated with the use of Ultomiris.

New Caplyta Strengths

To better treat patients who have liver conditions or who take certain other drugs, the FDA has approved two lower strengths of Caplyta® (lumateperone – Intra-Cellular Therapies). On April 26, 2022, both 10.5mg capsules and 21mg capsules were approved. Caplyta is an atypical antipsychotic drug that affects blood levels of three neurotransmitters (dopamine, glutamate, and serotonin). As once daily 42mg capsules, it initially was FDA approved in December 2019, for treating adults who have schizophrenia. Two years later, it gained an additional indication as therapy — either alone or along with lithium or valproate — for adults who have bouts of depression that accompany bipolar I and bipolar II disorder. Side effects can include dizziness, dry mouth, nausea, and sleepiness. A boxed warning on its labeling reminds patients and prescribers that no atypical antipsychotic should be used to manage psychoses related to dementia in elderly patients because their chances of death are increased. Launch for the new strengths is planned for the middle part of 2022.

Pediatric Indication Extended for Veklury

The FDA expanded the use of Veklury® (remdesivir) injection, Gilead’s antiviral for treating COVID-19, on April 25, 2022. Already approved for adults and teens, it now can be used to treat children as young as 28 days old who weigh 3kg (about 7 pounds) or more. Patients may be in the hospital or they may be outpatients who have mild or moderate COVID-19 and who are at increased risk for progressing to severe infection. The recommended dose for patients who weigh between 3kg and 40kg (88 pounds) is 5mg given by IV infusion on the first day, followed by 2.5mg per day for a total of three, five or 10 days, depending on the patient’s condition and site of treatment. For patients weighing less than 40kg, only the powdered form of Veklury for reconstitution and dilution is approved: the concentrated ready-to-dilute solution form cannot be given to children.

Broader Access to Oral COVID-19 Treatments

Pharmacies that are enrolled in the federal antiviral distribution program now are able to obtain supplies of Paxlovid™ (nirmatrelvir tablets and ritonavir tablets – Pfizer) and Lagevrio™ (molnupiravir capsules – Merck) directly from the federal government offices that manage the drugs’ distribution. Additionally, the number of dispensing locations is being increased to an eventual goal of 40,000. More sites that are authorized to test individuals for COVID-19 infection and offer immediate treatment at no cost for those who show positive results are being established, as well. Both drugs have emergency use authorizations (EUA) for patients who have mild-to-moderate COVID that could become severe, but that does not require hospital care. Paxlovid can be used by patients who are at least 12 years old; Lagevrio is limited to those aged 18 years and older. Treatment with either regimen should begin no later than five days after the onset of symptoms. Neither should be taken for longer than five days. Detailed prescribing information is in Paxlovid’s fact sheets for healthcare providers and patients; and in fact sheets for providers and patients of Lagevrio.

Recall: Accupril

Pfizer recalled five lots of Accupril® (quinapril) tablets to the consumer level on April 22, 2022. As with multiple previous recalls, this one also is due to unacceptably high levels of a nitrosamine contaminant. An angiotensin-converting enzyme (ACE) inhibitor, Accupril treats hypertension and heart failure.

Bristol Myers Squibb’s Camzyos™ (mavacamten)

The U.S. Food and Drug Administration (FDA) approved Bristol Myers Squibb’s Camzyos™ (mavacamten) on April 28, 2022. Camzyos, an allosteric and reversible inhibitor selective for cardiac myosin, was approved to treat adults who have symptomatic New York Heart Association (NYHA) class II or III obstructive hypertrophic cardiomyopathy (oHCM) to improve functional capacity and symptoms. It will be available in 2.5mg, 5mg, 10mg and 15mg oral capsules with a recommended starting dose of 5mg once daily. Since dosing takes weeks to reach therapeutic levels, maintenance doses will be individualized based on clinical assessment and echocardiogram readings with flow charts provided in the prescribing information. Camzyos comes with a boxed warning highlighting that patients with heart failure should be monitored to ensure their left ventricular ejection fraction (LVEF) is not <55% before and during treatment. An additional boxed warning alerts patients to be aware of potential drug interactions, including with over-the-counter (OTC) medications that are metabolized by CYP2C19 and CYP3A4 enzymes, which could lead to loss of effectiveness or heart failure. Prescriber certification and patient enrollment are required due to a risk evaluation and mitigation strategy (REMS) program because of the risk of heart failure due to systolic dysfunction. Camzyos will be available in limited distribution through a small network of specialty pharmacies, but it is unclear at this time if Accredo will have access.

Camzyos at a glance

• Brand (Generic) Name: Camzyos (mavacamten)
• Manufacturer: Bristol Myers Squibb
• Date Approved: April 28, 2022
• Indication: for the treatment of adults who have symptomatic New York Heart Association (NYHA) class II or III obstructive hypertrophic cardiomyopathy (oHCM) to improve functional capacity and symptoms
• Dosage Forms Available: 2.5mg, 5mg, 10mg and 15mg oral capsules
• Launch Date: Not known at this time
• Estimated Annual Cost: The estimated annual cost is $89,500 with a wholesale acquisition cost (WAC) of $245.20 per capsule
• Hypertrophic cardiomyopathy is a chronic, progressive genetic condition in which excessive contraction of the heart muscle and reduced ability of the left ventricle to fill can lead to the development of debilitating symptoms and cardiac dysfunction.
• HCM is estimated to affect one in every 500 people. Approximately 160,000 to 200,000 people have been diagnosed with symptomatic oHCM across the U.S. and the European Union (EU). Before Camzyos, the condition had no existing effective drug treatment options beyond limited symptomatic relief.
• The most frequent cause of HCM is mutations in the heart muscle proteins of the sarcomere (a structural protein of certain muscle tissue). In HCM patients, exertion can result in fatigue or shortness of breath, interfering with a patient’s ability to participate in activities of daily living. HCM has also been associated with increased risks of atrial fibrillation, stroke, heart failure and sudden cardiac death, with mortality among HCM patients shown to be approximately three-fold higher than the U.S. general population at similar ages.
• Approval was based on the EXPLORER-HCM pivotal study. At week 30, 37% of patients treated with Camzyos showed improvement across primary endpoint markers that included mixed venous oxygen tension (pVO2) by 1.5mL/kg/min or more, plus at least one NYHA class or improvement of pVO2 by 3.0 mL/kg/min or more without worsening in NYHA class vs. 17% of participants in the placebo group.
• Currently, treatment for HCM is based on symptomatic relief and prevention of sudden cardiac death with guideline-recommended initial pharmacological therapies including β-blockers or non-dihydropyridine calcium channel blockers. Heart rhythm drugs, such as disopyramide, often are added for individuals who are refractory to first-line therapy.
• Camzyos is a designated Breakthrough Therapy and Orphan Drug

Ukoniq Removed from the Market

In February 2021, TG Therapeutics received the FDA’s Accelerated Approval for Ukoniq® (umbralisib) tablets as late-line therapy to treat certain marginal zone lymphomas (MZL) and follicular lymphomas (FL). After further analysis of the results from clinical trials for those indications and with new data from studies of patients who have chronic lymphocytic leukemia (CLL), the U.S. Food and Drug Administration (FDA) determined that the risk of death actually increased when Ukoniq was used. Therefore, TG Therapeutics withdrew it from the U.S. market. Additionally, a request for FDA review of U2 (the combination of Ukoniq and an investigational drug, ublituximab) to treat CLL and small lymphocytic lymphoma (SLL) also has been withdrawn. Results from the pivotal clinical trials showed that U2 was less effective in prolonging overall survival (OS) than treatment with an FDA-approved regimen for the initial treatment of CLL — Gazyva® (obinutuzumab) injection and Leukeran® (chlorambucil) tablets.