April 6, 2022

Vijoice Accelerated approval

Novartis received Accelerated Approval from the U.S. Food and Drug Administration (FDA) for Vijoice® (alpelisib) tablets on April 5, 2022. It is the first drug approved to treat phosphoinositide 3-kinase CA (PIK3CA)-Related Overgrowth Spectrum (PROS), a group of extremely rare conditions that cause abnormal development in blood and lymphatic vessels, as well as in other body tissues. Vijoice is a kinase inhibitor indicated to treat patients who are at least two years old and who need systemic therapy for severe cases of PROS. Recommended once-daily doses are 50mg for patients between two years and 18 years old and 250mg for older patients. Novartis plans to launch 28-tablet boxes of blister-packed 50mg, 125mg or 200mg strengths of Vijoice within about one week. Here is its complete prescribing information.

At a Glance:

• Brand (Generic) Name: Vijoice (alpelisib)
• Manufacturer: Novartis
• Date Approved: April 5, 2022
• Indication: for the treatment of adults and pediatric patients 2 years of age and older who have severe manifestations of PROS and who require systemic therapy
• Dosage Forms Available: 50mg, 125mg and 200mg oral tablets
• Launch Date: within about one week
• Estimated Annual Cost: Not yet available
• PROS includes a number of disorders caused by spontaneous, not inherited, mutations in the PIK3CA gene, which helps to regulate cell growth and survival. As a result, some body parts may grow too quickly or get too large.
• The number of patients who have a PROS condition is difficult to establish. Novartis estimates that one or more of the disorders affects about 14 individuals per one million – fewer than 5,000 people in the United States.
• Symptoms can include pain, scoliosis, seizures, blood coagulation problems and neurological deficits. The brain, heart and kidneys frequently are damaged. Some patients may have unequal facial features, different size arms and legs or extremely large fingers and toes.
• Mutations in PIK3CA genes are associated with developing several types of solid-organ cancers.
• By blocking a key enzyme, Vijoice helps to restrict tissue overgrowth.
• Previously, pharmaceutical treatment for PROS was limited to symptom management. Surgery or interventional radiology may be used to remove tissue overgrowth.
• A retrospective review of medical chart data for 37 patients using Vijoice to treat PROS prompted the FDA’s Accelerated Approval for it. After 24 weeks, 23 patients responded to treatment, with 10 patients having at least a 20% decrease in the total size of abnormal growths. Reductions also were seen in pain, fatigue, asymmetrical limbs and coagulation abnormalities.
• The most common side effects reported by patients were generally manageable diarrhea, sores in the mouth and elevated blood sugar levels.
• Under the brand name, Piqray®, Novartis has sold alpelisib since May 2019. Piqray is taken at a dose of 300mg/day along with Faslodex® (fulvestrant), to treat patients who have advanced or metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer that has mutations in PI3KC.
• Because the approval was accelerated, the FDA requires additional information to confirm the effectiveness and safety of Vijoice before it is fully approved.

Fintepla Receives New Indication

UCB was granted U.S. Food and Drug Administration (FDA) approval on March 25, 2022, for a new indication for Fintepla® (fenfluramine) oral solution. It now is indicated to treat patients as young as two years old who have seizures resulting from Lennox-Gastaut syndrome (LGS). It also is approved for treating seizures associated with Dravet syndrome (DS) for patients in the same age range. Both conditions are rare, but severe, forms of epilepsy. Around 48,000 Americans have LGS, which usually is diagnosed before patients are six years old. DS, typically caused by spontaneously mutated genes, usually is apparent within the first 12 to 18 months of life. It is estimated to affect one in 20,000 to one in 40,000 live births. To treat either condition, the initial dose of Fintepla is 0.1mg/kg twice daily. If necessary, doses can be increased on a weekly basis to the recommended maintenance level of 0.35mg/kg twice daily, with a maximum daily dose of 26mg. If the patient also is taking Diacomit® (stiripentol) oral suspension and Onfi® (clobazam) tablets, the suggested upper limits of dosing are reduced to 0.2mg/kg and no more than 17mg/day. A C-IV controlled substance, Fintepla is dispensed under a risk evaluation and mitigation strategy (REMS) because it has the potential to cause valvular heart disease and/or pulmonary artery hypertension. As outlined in a boxed warning on its labeling, patients taking it should have an echocardiogram before treatment begins and then echocardiograms should be repeated periodically during therapy and even after treatment ends. A 360mL (792mg) bottle of Fintepla retails for about $17,000.

Cabenuva Receives FDA Approval to Treat Teens

The use of Cabenuva (co-packaged cabotegravir extended-release injection and rilpivirine extended-release injection), now includes patients who are at least 12 years old. The FDA approved the expansion for ViiV Healthcare’s HIV-1 therapy, which combines an integrase strand transfer inhibitor (INSTI) and a non-nucleoside reverse transcriptase inhibitor (NNRTI), on March 29, 2022. To be eligible for treatment with it, patients must weigh 35kg (77 pounds) or more, they must not have had failures with previous HIV-1 treatment and their viral loads must be less than 50 copies of HIV-1 RNA/mL due to a current stable anti-HIV-1 regimen. Cabenuva is dispensed in boxes containing individual single-dose vials of cabotegravir and rilpivirine. Doses are given once a month or once every two months as separate intramuscular (IM) injections by a health professional in a healthcare setting. A one-month long lead-in with the oral drugs Vocabria (cabotegravir) and Edurant® (rilpivirine) now is optional for all patients who start on Cabenuva, but some prescribers may recommend a phase-in period to assure that patients do not have severe reactions to the medications. In a very small study of adolescents, over 60% of patients who got either of Cabenuva’s components reported adverse effects – primarily pain at the injection site and insomnia. Most reactions were relatively minor and temporary, however; and only one (of 23) participants stopped treatment due to a side effect.

New Dose Form for Triumeq

ViiV won another FDA approval on March 30, 2022, when Triumeq PD (abacavir 60mg/dolutegravir 50mg/lamivudine 300mg) dispersible tablets were approved. They treat HIV-1 infections for children who weigh between 10kg (22 pounds) and 25kg (55 pounds). Daily dosing is based on weight — starting at four tablets once per day for children who weigh at least 10kg and increasing to five tablets for those weighing between 14kg (about 31 pounds) and 20kg (44 pounds) and then to six tablets for those between 20kg and 25kg. Triumeq PD tablets are dissolved in 20mL of water and consumed within one-half hour. A measured dose cup is included with each 90-tablet bottle of Triumeq PD. On the same day, the FDA allowed ViiV to extend the use of regular Triumeq tablets to patients whose weight is at least 25kg. The two formulations are not interchangeable. Labeling for both has a boxed warning that stopping lamivudine may induce hepatitis B (HBV) flares for patients who have both HIV and HBV, even if HBV is not active. All patients should be tested for HBV before starting treatment with Triumeq. Because abacavir has caused serious, sometimes deadly, hypersensitivity reactions among patients who have an HLA-B*5701 allele, all patients should be tested for the allele before treatment is initiated. No pricing or launch plans for Triumeq PD have been released.

Camcevi Launched

Camcevi™ (leuprolide) injectable emulsion, which was FDA approved in May 2021, has been released to the U.S. market. A gonadotropin-releasing hormone (GnRH) receptor antagonist, it is indicated for treating adults who have advanced stages of prostate cancer. It works by decreasing the amounts of testosterone in the body. At a dose of one (42mg) subcutaneous (SC) injection once every six months, it must be administered by a healthcare professional. Although other extended-release leuprolide products, such as Eligard® (leuprolide acetate – Tolmar Pharmaceutical) suspension for SC injection and Lupron Depot® (leuprolide acetate for depot suspension – AbbVie), have been available to treat prostate cancer for many years, Camcevi is a new salt form of leuprolide that may result in lower testosterone levels than some other drugs do. Patients using Camcevi may be more likely to have high blood sugar, which could lead to diabetes. The risk of CV problems, including heart attacks, also may be elevated. In clinical trials, some patients using Camcevi had temporary increases in their cancer symptoms, such as bone pain and urine blockage. Developed by Foresee Pharmaceuticals, Camcevi is distributed the United States by Accord BioPharma in single-dose prefilled syringe kits.

Tlando Approved

On March 28, 2022, the FDA approved a new dosage form of testosterone. Tlando™ (testosterone undecanoate) capsules were approved to replace testosterone for adult men who have hypogonadism (deficiencies or absences of natural testosterone). According to the manufacturer, up to one-half of men who have type 2 diabetes and/or obesity and about one-third of men who are 45 years or older are believed to have hypogonadism, which should be verified by blood tests before beginning Tlando. The dose is 225mg (two capsules) taken twice a day along with food. Testosterone levels should continue to be checked during treatment with it. A boxed warning cautions that blood pressure also should be monitored frequently for patients taking it, since Tlando may cause hypertension that could trigger heart attacks, strokes or cardiovascular (CV)-related death. Although the drug was developed by Lipocine Inc., Antares Pharma will market Tlando in the U.S. beginning in the second quarter of 2022. Its price is not yet available.

New Strength for Ozempic

A 2mg strength dose of Ozempic® (semaglutide) injection, Novo Nordisk’s glucagon-like peptide-1 (GLP-1) analog, was FDA approved on March 28, 2022. Injected once a week, it is indicated along with diet and exercise to treat adults who have type 2 diabetes that is not adequately controlled by smaller doses. Ozempic lowers blood glucose levels through several pathways, including slowing glucose absorption after meals, decreasing glucagon production and promoting insulin secretion from the pancreas. An additional approval to decrease the chances of heart attack, strokes, other adverse CV events and death for adults who have both type 2 diabetes and CV disease was FDA approved in January 2020. The higher strength dose is intended for patients whose hemoglobin A1C (HbA1c) remains above their target ranges despite active treatment with 1mg of Ozempic/week. Recommended dosing for new patients begins at 0.25mg once a week for four weeks and then increases to 0.5mg for at least four weeks. If blood sugar control is still inadequate, doses can be raised to 1mg for four weeks or longer, and then to 2mg, if necessary. Like all GLP-1 agonists, Ozempic has a boxed warning about tumors of the thyroid gland (thyroid C-cell tumors) that have occurred among laboratory animals treated with some GLP-1 receptor agonists in preclinical studies. However, whether or not GLP-1s cause humans to develop thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), is not yet known. Patients with MCT, individuals with close family members who have thyroid C-cell tumors and patients with Multiple Endocrine Neoplasia syndrome type 2 should not use them. Single-dose, self-injector pens that deliver 2mg of Ozempic should be available in the U.S. shortly.

Second COVID Booster Authorized

The FDA is endorsing a second COVID-19 booster for certain segments of the American population. On March 29, 2022, an additional intramuscular (IM) injection of either 0.3mL of Pfizer/BioNTech’s Comirnaty® (COVID-19 Vaccine, mRNA) suspension, or 0.5mL of Moderna’s Spikevax® (COVID-19 Vaccine, mRNA) suspension was authorized for patients who are 50 years old or older or who are at least 12 years old and have an immunocompromising medical condition. Four months must have elapsed since the administration of the first booster shot. Either vaccine can be used regardless of which was given previously. Links to information about available vaccines are here.

Sotrovimab Use Limited in Many Areas

The Centers for Disease Control and Prevention (CDC) temporarily has stopped sending supplies of sotrovimab to multiple states and territories where the dominant strain of COVID-19 now is Omicron BA.2. Sotrovimab has an emergency use authorization (EUA) from the FDA for treating mild-to-moderate COVID-19 for high-risk patients who are 12 years old or older and who weigh 40kg (88 pounds) or more. However, laboratory testing shows that the infused monoclonal antibody has little effectiveness against COVID’s Omicron BA.2 variant. Therefore, the FDA temporarily is rescinding its EUA for areas where 50% or more of new cases are BA.2. Using sotrovimab against BA.2 will not help patients to recover, and viral resistance to its effectiveness for other strains of the virus may develop. Presently, numerous states and territories are affected, and others will be added as the variant spreads. The CDC states that other antiviral medications, such as Paxlovid™ (nirmatrelvir tablets and ritonavir tablets), molnupiravir and bebtelovimab, that have EUAs for treating COVID-19, still can be used for patients who have any of COVID‘s presently recognized Omicron variants. They remain available for all parts of the country. More information is in sotrovimab’s current Fact Sheet and an FDA update. In addition, the U.S. Department of Health and Human Services (HHS) has established a new website that patients can use to find sources for COVID treatment near them.

Recall

Symjepi

Adamis Pharmaceuticals recalled four lots of Symjepi® (epinephrine) prefilled syringes on March 21, 2022, after complaints that some syringes have clogged needles. Symjepi is kept on hand by individuals who have severe allergies and may need emergency treatment for allergic reactions. Less-than-full doses could be life threatening.