New Pediatric Indications Approved for Cosentyx
Novartis’ Cosentyx® (secukinumab) injection was awarded two new pediatric indications from the FDA on Dec. 22, 2021. It now can be used to treat children who are at least four years old for active enthesitis-related arthritis (ERA) and children who are at least two years old for active juvenile psoriatic arthritis (JPsA). ERA is a form of juvenile idiopathic arthritis (JIA) that causes inflammation, pain and swelling at the places where ligaments and tendons attach to bones. Generally diagnosed for older children and teenagers, it is slightly more common for boys than girls. In May 2021, Cosentyx also was FDA approved for treating children as young as six years old who have moderate-to-severe plaque psoriasis. Dosing for pediatric patients is based on weight. For the new indications, patients who weigh between 15kg (33 pounds) and 50kg (110 pounds) need 75mg; for those weighing over 50kg, the dose is 150mg. Doses are given subcutaneously (SC), beginning with one each week for five weeks and then changing to one every four weeks. Although the higher dose is available in single-dose vials, prefilled pen devices and prefilled syringes; the 75mg dose is marketed only as prefilled syringes. Cosentyx also has indications for the treatment of adults who have ankylosing spondylitis (AS), psoriatic arthritis (PsA) or plaque psoriasis. For its revised prescribing information, check here.
Generic and Authorized Generic for Narcan Now Available
Teva revealed on Dec. 22, 2021, that it has introduced the first generic for Narcan® (naloxone – Emergent Biosolutions) Nasal Spray, 4 mg, in the United States. On the same day, Sandoz also announced it has released an authorized generic (AG) version. An opioid agonist, naloxone provides temporary reversal of opioid overdoses in emergency settings. The generic and the AG both already are being shipped as packages of two single-dose spray devices to healthcare facilities and retail pharmacies. One dose (one spray) of naloxone should be given as soon as an overdose is observed or suspected, based on the patient’s breathing difficulty and/or unconsciousness. Emergency medical help should be requested immediately after the first spray. One additional spray can be given every two to three minutes, if necessary, until professional assistance arrives. Teva has not yet announced its pricing for the generic. AGs essentially are brand drugs that are repackaged with generic-looking labels. Although an exact price for Sandoz’s naloxone nasal spray is not readily available, AGs typically cost less than their branded counterparts. Many physicians prescribe naloxone along with opioid prescriptions for patients considered at high risk for overdoses. In the U.S., naloxone nasal spray, 4mg, can be dispensed without a prescription or it can be prescribed for a caregiver of an at-risk patient, depending on state regulations. Annual sales for Narcan Nasal Spray, 4mg were estimated at $325 million for 2021.
Shipping Halted for Some Anti-COVID Antibodies
On Dec. 23, 2021, the FDA and the Health and Human Services (HHS) Department’s Assistant Secretary for Preparedness and Response (ASPR) announced that the Omicron strain of COVID-19 may be resistant to some of the monoclonal antibodies (mAbs) that have emergency use authorizations (EUAs) for treating it. Etesevimab alone (Eli Lilly), bamlanivimab and etesevimab administered together (Eli Lilly) and REGEN-COV (casirivimab and imdevimab given together – Regeneron) seem not to have significant activity against the Omicron variant of COVID-19. Therefore, the ASPR, which distributes the antibodies to healthcare facilities, has stopped sending them, temporarily. Another mAb, sotrovimab (GlaxoSmithKline), does appear to be effective against Omicron, so it will continue to be released for treating patients. However, some states already are beginning to report shortages of sotrovimab. Noting that the situations in different areas as well as in individual healthcare settings can vary greatly and change rapidly, the FDA has posted links to current information on COVID-19, its treatments, vaccines and other facts on their EUA page.
Boxed Warning Removed for Tymlos
When it originally was FDA approved in 2017, Tymlos® (abaloparatide – Radius Health) injection was required to have a boxed warning on its label that using it may increase the risk of osteosarcoma (bone cancer). A human parathyroid hormone related peptide (PTHrP [1-34]) analog, it treats postmenopausal women who are at high risk for bone fractures due to osteoporosis. Based on results from continued clinical trials, the FDA now is allowing the removal of the boxed warning, although Tymros still is not recommended for patients who have a high risk of osteosarcoma. Given as one 80mcg SC injection into the abdomen each day, Tymlos is dispensed in a 30-dose prefilled pen device. In clinical studies, using it decreased the incidence of new fractures in the spine and other bones, and increased both bone mineral density (BMD) and a specific blood marker indicating new bone formation. Its use for longer than a cumulative period of two years has not been studied. Because it may cause a sudden drop in blood pressure when the patient stands up, at least the first few doses of Tymlos should be given where the patient can sit or lie down if she becomes dizzy or nauseated after a dose. It also may cause elevated calcium levels in the blood and/or urine. Look here for its full prescribing information.
On Dec. 27, 2021, Padagis, the manufacturer of Nitroglycerin Lingual Spray 400mcg/spray, recalled three lots of their 12gm bottles to the consumer level because some of the spray devices may not be assembled properly. Doses of the drug, used to relieve acute chest pain associated with coronary artery disease, may not be delivered accurately. The recalled devices are sold in the U.S. under the Perrigo product. For more information, a press release from Padagis is here.
Adbry™ (tralokinumab-ldrm – LEO Pharma)
A monoclonal antibody that inhibits the action of interleukin-13 (IL-13), Adbry™ (tralokinumab-ldrm – LEO Pharma) injection, was approved by the U.S. Food and Drug Administration (FDA) on Dec. 27, 2021. It will be available in February 2022, as second-line or later treatment for patients who are at least 18 years old and who have moderate-to-severe atopic dermatitis that has not been controlled by standard therapies. Administered subcutaneously (SC), recommended treatment with Adbry begins with one 600mg dose (four injections at the same time) and then 300mg (two injections at the same time) once every two weeks. After 16 weeks, patients who weigh less than 100kg (220 pounds) and whose skin has cleared or nearly cleared may be switched to 300mg once every four weeks. Adbry can be used alone or along with topical products. It will be available through a large network of specialty pharmacies that includes Accredo. Pricing has not yet been announced. Here is its prescribing information.
At a Glance
- Brand (Generic) Name: Adbry (tralokinumab-ldrm)
- Manufacturer: LEO Pharma
- Date Approved: Dec. 27, 2021
- Indication: to treat moderate-to-severe atopic dermatitis for adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable
- Dosage Forms Available: single-dose 150mg prefilled syringes for SC injection packed in boxes of two or four syringes
- Launch Date: February 2022
- Estimated Annual Cost: Pricing information is not yet available.
- Atopic dermatitis is a common form of eczema, a group of chronic skin diseases that involve inflammation and cause itchy, irritated bumps, crusts and scales on the skin. It usually begins in childhood, with most patients having a first episode before the age of five years. Symptoms may improve and worsen unpredictably. Inflammation and scratching eventually can thicken and toughen the skin.
- According to the Asthma and Allergy Foundation of America, around 7.3% of American adults (about 18 million people) have atopic dermatitis. Moderate-to-severe forms of the condition are estimated to affect approximately two of every five patients aged 18 years or older.
- Adbry interferes with IL-13 to block the release of inflammatory substances.
- In three clinical trials comparing Adbry to placebo, the Eczema Area and Severity Index (EASI) score improved by at least 90% from baseline for between 12% and 22% more of actively treated patients than those receiving placebo injections.
- Initial therapy for atopic dermatitis usually is a topical corticosteroid, with higher potency products used to treat more severe forms of the condition. A calcineurin inhibitor, such as Elidel® (pimecrolimus) cream may be used for patients who cannot use a corticosteroid or whose atopic dermatitis has not been cleared by topical corticosteroid treatment.
- Dupixent® (dupilumab – Sanofi/Regeneron) injection, which is FDA approved for treating patients as young as six years old who have moderate-to-severe atopic dermatitis that is not responding to topical therapy, is an interleukin-4 alpha receptor (IL-4Rα) blocker.
Illuccix Approved for Prostate Cancer Imaging
A new agent for imaging prostate cancer, Telix Pharmaceuticals’ Illuccix ® (TLX591-CDx), was approved by the U.S. Food and Drug Administration (FDA) on Dec. 17, 2021. The prostate-specific membrane antigen is radiolabeled with gallium-68 (68Ga) gozetotide, also called PSMA-11, before a positron emission tomography (PET) imaging procedure. The recommended dose of between 111 MBq and 259 MBq is delivered in one quick intravenous (IV) injection. It should be given between 50 minutes and 100 minutes after mixing for patients whose prostate cancer is presumed to have metastasized or returned. Like all radioactive pharmaceuticals, Illuccix will be handled under precise conditions by imaging centers, hospitals and nuclear pharmacies that have specifically trained staff, specialized equipment and strict protocols for using and discarding radioactive substances. Telix has agreements in place with distributors that it believes will be able to serve 85% of facilities that can use Illuccix. No exact launch date is available. Complete prescribing information is here.
FDA Approves Dartisla ODT
The FDA has approved a new dose form of glycopyrrolate as a new drug. On Dec. 16, 2021, Edenbridge Pharmaceutical received the approval for Dartisla ODT (glycopyrrolate) orally disintegrating tablets. It is indicated for use only in combination with other drugs as treatment for adults who have stomach ulcers. It inhibits the action of acetylcholine on parietal cells in the stomach and decreases the volume and acidity of gastric secretions. The recommended dose is one tablet (1.7mg) that is dissolved on the tongue two or three times each day with a maximum daily limit of four tablets (6.8mg). Dartisla ODT should be taken without any additional liquid and doses should be taken one hour or more before eating or two hours or more after consuming food. An anticholinergic agent that has been FDA approved since the early 1960s, glycopyrrolate in inhaled, injected and other oral forms is used for a number of additional disorders, that include chronic respiratory conditions and excessive drooling associated with some neuromuscular conditions. Certain patients, including individuals who have bleeding ulcers, glaucoma or myasthenia gravis, should not use any glycopyrrolate product. An early 2022 launch is expected for Dartisla ODT, but its cost has not been announced.
Pediatric Indication Extended for Oxbryta
On Dec. 17, 2021, the FDA expanded its Accelerated Approval for Oxbryta® (voxelotor – Global Blood Therapeutics) tablets to treat children between the ages of four years and 12 years old. Originally introduced to the U.S. market late in 2019 for patients over the age of 12 years, it is the only available sickle hemoglobin polymerization inhibitor. By adhering to hemoglobin, which then attracts more oxygen and stabilizes red blood cells (RBCs), it treats the cause of sickle cell disease, not just its symptoms. It also may decrease the thickness of blood and the tendency of blood cells to deform (sickle) while increasing RBC flexibility. On the same day, the FDA also approved a new dosage form, tablets for oral suspension, which can be dissolved in lukewarm water or another clear liquid, making treatment easier for patients who have trouble swallowing whole tablets. With an estimated total patient population for sickle cell disease of around 100,000 Americans, approximately 16,000 U.S. children between the ages of four years and 12 years old are believed to be candidates for treatment with Oxbryta. Recommended dosing for patients who are 12 years and older is 1,500mg once a day. Once-daily doses for younger children vary according to body weight – beginning at 600mg for patients weighing at least 10 kg (22 pounds) and increasing to 1,500mg for those who weigh 40kg (88 pounds) or more. Because it initially received the FDA’s Accelerated Approval, further testing needs to be completed successfully before full approval is granted. Global Blood Therapeutics is conducting additional active clinical trials for treating children as young as nine months old. Look here for Oxbryta’s updated prescribing information.
Xarelto Approved for Children and Teens
Pediatric indications for preventing and treating blood clots were approved by the FDA on Dec. 20, 2021, for Janssen’s Xarelto® (rivaroxaban) tablets and oral solution. Its new prevention indication is for patients who are at least two years old and who have had a Fontan procedure – open-heart surgery to bypass a nonfunctional heart ventricle. Children who need the operation typically undergo it before they are three years old. As treatment, Xarelto now can be used after five days of therapy with an injected or infused anticoagulant for newborns who weigh at least 2.6kg (about six pounds), as well as for older children and teens. For patients over the age of 17 years, Xarelto is used by itself to prevent and treat multiple types of blood clots, including deep vein thrombosis (DVT) and pulmonary embolism (PE). With a low dose of aspirin, it also is indicated for adult use to lower the risk of serious adverse events for patients who have coronary artery disease (CAD) or peripheral artery disease (PAD). Pediatric doses, which are based on body weight, start at 0.8mg three times a day and increase to 3mg three times a day for children who weigh less than 12kg (about 26 pounds) and who take the oral solution form of Xarelto. Patients who weigh 12kg or more either can continue the oral solution or switch to tablets, which need to be taken only once or twice daily. The upper limit on dosing is 20mg per day for patients who weigh 50kg (110 pounds) or more. All doses should be taken with a meal or snack. Stopping Xarelto or any other direct-acting oral anticoagulant (DOAC), may result in blood clots, as detailed in a boxed warning on their labels. Patients who have an invasive spinal procedure while taking a DOAC, are at higher risk of spinal damage that could cause permanent paralysis. Updated prescribing information is here.
Caplyta Gets Second Indication
Caplyta® (lumateperone – Intra-Cellular Therapies) capsules initially was FDA approved two years ago to treat adults who have schizophrenia. On Dec. 17, 2021, the FDA also approved it for treating adults who have bouts of depression that accompany bipolar I and bipolar II disorder – either alone or along with lithium or valproate. For both indications, the recommended dose is one capsule (42mg) daily. By influencing levels of three neurotransmitters (dopamine, glutamate and serotonin), Caplyta works differently from other atypical antipsychotic drugs that affect fewer neurotransmitters. In clinical trials, bipolar depression was relieved substantially more by Caplyta as opposed to a placebo at six weeks of treatment. Actively treated patients reported more generally mild side effects, such as dizziness, dry mouth, nausea and sleepiness; but changes in blood cholesterol, blood sugar and weight did not differ significantly between the two groups of participants. A boxed warning on Caplyta’s 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. In addition, children, teens and young adults who use an antidepressant may be more prone to consider or attempt suicide. Although Caplyta is not approved for pediatric patients, young adults taking it should be observed for any signs of suicidal behavior. For revised prescribing information, go here.
New Indication for Otezla
The FDA added an indication on Dec. 20, 2021, for Amgen’s phosphodiesterase-4 (PDE-4) inhibitor, Otezla® (apremilast). Originally FDA approved in 2014 to treat adults who have psoriatic arthritis (PsA), it later was also approved as treatment for adult patients who have mouth sores resulting from Beçhet’s disease, a rare condition that causes inflammation in blood vessels. Now, Otezla is indicated for treating all adults who have any degree of plaque psoriasis and who are eligible for phototherapy or systemic therapy. About 5 million U.S. adults are believed to have mild-to-moderate forms of plaque psoriasis, with another 3 million experiencing more severe symptoms. To treat any stage of the condition, the recommended maintenance dose is 30mg of Otezla every morning and 30mg every evening, after doses start at 10mg/day on the first day and then increase by 10mg per day over the next five days. In a clinical study, 21.6% of patients taking a 16-week course of Otezla’s maintenance dose for less severe psoriasis symptoms achieved the preset outcome as compared with 4.1% of patients taking placebo. For the symptom of whole body itching the numbers were 43.3% and 18.6%, respectively. Go here for current prescribing information.
Second Biosimilar to Lantus Approved
Eli Lilly was given FDA approval on Dec. 17, 2021, for Rezvoglar (insulin glargine-aglr). A long-acting (basal) insulin, it is indicated along with a shorter-acting insulin to treat type 2 diabetes for adults and type 1 diabetes for patients of any age. Administered subcutaneously (SC) at about the same time every day through pen devices, doses vary according to the patient’s blood sugar readings, exercise amounts, meal timing and overall health. Injections should be given into the abdomen, thigh or upper arm, with sites changed frequently to limit the chances that abnormalities will occur in the fats or proteins under the skin at places where Rezvoglar is injected. Insulin pens should not be shared among patients. Even though it is the second biosimilar for Lantus (insulin glargine – Sanofi), it cannot automatically be switched with Lantus. Prescriptions will need to be written specifically for Rezvoglar for it to be dispensed. At the end of July 2021, Semglee® (insulin glargine-yfgn) and an unbranded insulin glargine product, which both are manufactured by Viartis/Biocon Biologics, were FDA-designated as the first automatically interchangeable insulins to Lantus. They have an exclusivity period that prevents the FDA from approving other substitutable insulin glargine products until 12 months from their launch in November 2021. Lilly has not announced how it plans to price or distribute Rezvoglar at this time.
FDA Approval for Yusimry
Another biosimilar, this one to the tumor necrosis factor (TNF) inhibitor, Humira® (adalimumab), also was FDA approved on Dec. 19, 2021. Named Yusimry™ (adalimumab-aqvh – Coherus BioSciences), it is indicated for the same conditions as Humira is — ankylosing spondylitis, plaque psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA) and ulcerative colitis (UC) for adults; Crohn’s disease for patients at least six years old and juvenile idiopathic arthritis (JIA) for patients aged two years and older. However, Yusimry is not interchangeable with Humira or with any of the other Humira biosimilars that already are FDA approved – Abrilada™ (adalimumab-afzb – Pfizer), Amjevita™ (adalimumab-atto – Amgen), Cyltezo® (adalimumab-adbm – Boehringer Ingelheim), Hadlima™ (adalimumab-bwwd – Samsung Bioepis), Hulio® (adalimumab-fkjp – Mylan/Fujifilm Kyowa Kirin Biologics) and Hyrimoz™ (adalimumab-adaz – Sandoz). All TNF inhibitors have a boxed warning that outlines the increased risks of cancer and serious infections that may be associated with their use. Prospective patients should be screened for tuberculosis (TB) before starting treatment and periodically while therapy continues. Under the terms of a settlement agreement with AbbVie, the manufacturer of Humira, Yusimry cannot be introduced in the U.S. until July 1, 2023, at the earliest.
New Lanreotide Product Approved
Cipla was awarded FDA approval on Dec. 17, 2021, for lanreotide injection, a competitor for the specialty drug, Somatuline Depot® (Ipsen Biopharmaceuticals). Approved as a new drug, not a generic, Cipla’s product will be available in the same strengths (60mg/0.2mL, 90mg/0.3mL and 120mg/0.5mL) single-dose prefilled syringes as Somatuline Depot. It also has the same indications for treating adults who have acromegaly or gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Doses are administered by healthcare providers as SC injections once every four weeks at 90mg/dose for acromegaly and 120mg/dose for GEP-NETs. After 12 weeks, doses for acromegaly may change depending on the patient’s levels of growth hormone and insulin growth factor-1. In the twelve months that ended on Oct. 31. 2021, IQVIA estimated that U.S. sales of Somatuline depot amounted to $867 million. Cipla has not yet released any pricing or launch details. Here is prescribing information.
Molnupiravir capsules, an oral antiviral drug for the treatment of COVID-19 infections, received an Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) on Dec. 23, 2021. It is authorized to treat patients who are at least 18 years old, who have tested positive for mild-to-moderate COVID-19 within the last five days, who have a high chance of worsening to a more severe infection and who have no other available treatment options. Patients take 800mg of molnupiravir (four capsules) every 12 hours for five days. The U.S. government is paying the manufacturers, Merck and Ridgeback Biotherapeutics, $700 per regimen for the 3 million treatment courses that should become available for use early in January. The first shipments are expected in the next few days to the wholesale company that will be distributing the drug. Fact sheets are available for prescribers here and patients here.
At a Glance
- Generic Name: molnupiravir
- Manufacturer: Merck/Ridgeback Biotherapeutics
- Date Approved: Dec. 23, 2021
- Indication: to treat mild-to-moderate COVID-19 for adults who have positive results from direct SARS-CoV-2 viral testing, who are at high risk for progressing to severe COVID-19, (including hospitalization or death) and for whom alternative COVID-19 treatment options authorized by FDA are either inaccessible or clinically inappropriate
- Dosage Forms Available: 200mg oral capsules
- Launch Date: late December 2021
- More than 51 million Americans have contracted COVID-19 and 810,000 have died from it since the pandemic was declared in early 2020. The highly contagious Omicron variant now is responsible for the majority of around 150,000 new infections diagnosed daily in the U.S.
- Taking an oral antiviral not only can help prevent patients from developing severe stages of COVID-19, they also may shorten the length of active infections. In addition, since they do not have to be administered in a healthcare facility, their use will help relieve pressure on overstrained hospitals and health providers.
- Molnupiravir is a nucleoside analog that infiltrates and disrupts viral RNA strands, inhibiting viral replication.
- In the phase III MOVe-OUT trial, more than 1,400 adults who were verified to have mild-to-moderate COVID-19 symptoms for five days or less were treated with molnupiravir capsules or placebo capsules at 12-hour intervals for five days. Participants also had one or more risk factors, such as diabetes, heart disease or obesity. In updated results, 6.8% of patients taking molnupiravir had been hospitalized and one had died by the 29th day after treatment began. Among the patients taking placebo, 9.7% needed hospital care and nine died within 29 days – a difference of about 30% between the two sets of patients.
- The percentages and types of adverse side effects, including diarrhea, dizziness and nausea, were comparable between the two groups.
- However, studies of laboratory animals showed that very large molnupiravir doses may interfere with the transition of cartilage into new bone in young animals, so it is not authorized for patients under the age of 18. Some animals also suffered damage to bone marrow, which resolved after treatment ended.
- Additionally, taking molnupiravir may harm a developing baby, making it unsuitable for patients who are pregnant. Women of childbearing age are advised to use an effective form of birth control during treatment and for at least four days after molnupiravir is stopped. After being treated with molnupiravir, male partners of women who could become pregnant should use contraception for at least 90 days.
- On Dec. 22, 2021, the FDA issued an EUA for Pfizer’s Paxlovid™ (nirmatrelvir) tablets, which are co-packaged with ritonavir, for the treatment of patients age 12 years old or older, weighing 40kg (88 pounds) or more, testing positive no more than five days previously for COVID-19, having mild-to-moderate symptoms and carrying a high risk of developing severe disease. In clinical studies, a five-day course of Paxlovid/ritonavir reduced the risk of death or hospitalization by nearly 90% for patients taking it.
On Dec. 22, 2021, the U.S. Food and Drug Administration approved the first small interfering RNA (siRNA) drug to treat high cholesterol.
Leqvio® (inclisiran – Novartis) injection will be added to dietary modifications and the highest bearable doses of an HMG-CoA reductase inhibitor (statin) to treat adults who have heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD), but whose current treatment has not lowered low-density lipoprotein cholesterol (LDL-C) levels adequately. It will be administered by a health provider using a prefilled syringe that contains the recommended dose of 284mg. The second dose should be three months after the first, and then doses are spaced at once every six months. Wholesale acquisition cost is $3,250/syringe. Novartis will launch Leqvio early in January 2022. It will only be available through specialty pharmacies and specialty distributors.
At a Glance
- Brand (Generic) Name: Leqvio (inclisiran)
- Manufacturer: Novartis
- Date Approved: Dec. 22, 2021
- Indication: as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults who have HeFH or clinical ASCVD, but who require additional lowering of LDL-C
- Dosage Forms Available: 284mg single-dose prefilled syringes
- Launch Date: January 2022
- Estimated Annual Cost: WAC of $9,750 for the first year, then $6,500 for subsequent years
- HeFH is a relatively rare, potentially severe hereditary condition – affecting approximately one of each 250 to 500 people in the United States. However, the FDA estimates that over 18 million Americans have ASCVD, which includes acute coronary syndrome, heart attacks, peripheral artery disease, strokes and other cardiovascular (CV) conditions. Despite using high doses of statin drugs, many patients who have one of the conditions cannot achieve optimal LDL-C levels.
- Leqvio promotes the deterioration of proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme that restricts the numbers of LDL-C receptors. As a result, more receptors are available in the liver to remove LDL-C from the blood.
- In three clinical studies of Leqvio compared to placebo, about 12% of over 3,600 enrolled patients had HeFH and 85% had ASCVD. Over both conditions, actively treated patients averaged LDL-C decreases between 40% and 51% as compared with slight increases (1% to 8%) among patients treated with placebo after 17 months (four injections).
- Injection site reactions were more likely for patients receiving Leqvio (8.2% vs 1.8%), but rates of other side effects, including breathing problems, diarrhea, joint pain and urinary tract infections were similar for Leqvio and placebo.
- Two monoclonal antibody drugs, Praluent™ (alirocumab – Regeneron) and Repatha™ (evolocumab – Amgen) inhibit PCSK9. Both have indications for primary hyperlipidemia, which includes HeFH, and reduction of CV events for certain patients. Either can be self-injected at intervals of two weeks or four weeks.
The U.S. Food and Drug Administration granted an Emergency Use Authorization (EUA) on Dec. 22, 2021, for Pfizer’s oral antiviral drug, Paxlovid™ (nirmatrelvir) tablets.
Blister-packed along with ritonavir tablets (as a booster), it will treat patients who are at least 12 years old, who weigh 40kg (88 pounds) or more, who have a positive test for COVID-19 with mild-to-moderate symptoms and who have a high risk of developing severe disease. Treatment should begin within five days of diagnosis. Recommended dosing is 300mg (two tablets) of Paxlovid plus one 100mg ritonavir tablet taken twice daily for five days. It does not prevent COVID-19 infections and Paxlovid should not be used for patients who are hospitalized with severe cases of the disease. Pfizer has manufactured many thousand doses, which it can begin sending out immediately. The U.S. government already has purchased enough Paxlovid for 10 million patients at a cost of $530 for each complete treatment package. The Biomedical Advanced Research and Development Authority (BARDA) division of the U.S. Department of Health and Human Services (HHS) will oversee distribution. Here is an EUA Fact Sheet for healthcare providers. One for patients and caregivers is here.
At a Glance
- Brand (Generic) Name: Paxlovid (nirmatrelvir) co-packaged with ritonavir
- Manufacturer: Pfizer
- Date Authorized: Dec. 22, 2021
- Indication: to treat mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) who have positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing and who are at high risk for progression to severe COVID-19, including hospitalization or death
- Dosage Forms Available: cartons containing 20 Paxlovid tablets (150mg each) packaged with 10 ritonavir tablets (100mg each)
- Launch Date: Dec. 22, 2021
- Over 800,000 Americans have died from COVID-19 since the pandemic was declared in early 2020 and currently around 150,000 cases are being diagnosed in the U.S. daily. The rapidly spreading Omicron variant now accounts for about three-quarters of new infections.
- Oral therapy taken soon after a mild-to-moderate infection with COVID-19 is diagnosed can help shorten the duration of the illness, lessen disease severity and reduce hospitalizations.
- Paxlovid, which targets SARS-CoV-2-3CL protease, an enzyme the virus needs to reproduce, will be taken along with ritonavir. A different type of protease inhibitor, ritonavir functions as a booster by slowing the metabolism of Paxlovid so that more of it stays active for longer periods.
- On Dec. 14, 2021, Pfizer released the final results from high-risk COVID-19 patients in its ongoing EPIC-HR clinical study of Paxlovid plus ritonavir. For patients who began taking the two-drug combination within three days of a mild-to-moderate COVID-19 diagnosis, the risk of dying or needing hospitalization by day 28 fell by 89%; for those starting within five days, by 88%, as compared to patients who took placebos. Among all participants, no actively treated patients died and fewer than 1% had to be hospitalized within 28 days of their first dose, but 6.5% of placebo-treated patients needed hospitalization and nine died.
- Adverse effects from Paxlovid/ritonavir treatment generally are mild and temporary. They include aching muscles, diarrhea, high blood pressure and changes in the ability to taste.
- Taking ritonavir may be associated with liver damage, so the Paxlovid/ritonavir regimen should be prescribed with caution for patients who have liver conditions, including hepatitis. Paxlovid is not recommended for patients who have kidney diseases.
- A second oral antiviral for COVID-19 also may be granted an EUA in the near future. On Nov. 30, 2021, members of the FDA’s Antimicrobial Drug Advisory Committee (ADAC) voted 13 to 10 to approve an EUA for Merck’s molnupiravir despite more modest results from its phase III MOVe-OUT trial. Among the patients taking molnupiravir, 6.8% were hospitalized or died compared to 9.7% of the placebo-treated patients – roughly a 30% reduction in risk of hospitalization or death. ADAC members who voted for authorization generally highlighted the unmet need for additional treatment options. The ‘no’ voters were concerned about some safety risks, including embryofetal toxicity and the drug’s effects on the formation of bone and cartilage development (based on animal studies), of the therapy as well as its modest efficacy.