Third Indication for Olumiant

Olumiant® (baricitinib) tablets, an oral Janus-Associated kinase (JAK) inhibitor that is marketed in the United States by Eli Lilly and Company, received a new indication on June 13, 2022, from the U.S. Food and Drug Administration (FDA). It has become the first systemic treatment for adult patients who have alopecia areata, an autoimmune condition that causes widespread hair loss because the body’s immune system destroys hair follicles.

Previous treatments involved topical products, such as minoxidil and corticosteroids, or injections of corticosteroids into the affected areas. Olumiant blocks JAK pathways, which relay inflammatory signals inside cells. In two clinical studies that enrolled over 900 patients who had 50% or less of their scalp hair for six months or longer, participants took 2mg or 4mg of Olumiant or a placebo tablet daily for nine months. As compared to 5% of the patients taking a placebo, up to 22% of those taking 2mg and as many as 35% of those taking 4mg achieved the primary endpoint, which was at least 80% scalp hair coverage.

The most common side effects among study patients who took Olumiant include upper respiratory infections (URIs), headaches, acne, and elevated cholesterol levels.

The recommended dose is 2mg once a day – increased to 4mg if needed and then shifted back to 2mg when an adequate amount of hair has been restored. A boxed warning is required by the FDA for all JAK inhibitors that are used to treat inflammatory conditions. It cautions that patients taking them may have a greater chance of dying, developing certain cancers, suffering cardiovascular (CV) events, having blood clots and acquiring severe infections. Patients also should be screened for tuberculosis (TB) before starting treatment with a JAK inhibitor and periodically during therapy.

Olumiant’s approval for alopecia was expedited under the FDA’s Breakthrough Therapy and Priority Review programs. It originally was approved by the FDA in June 2018, for second-line treatment of rheumatoid arthritis (RA) in adults. In May 2022, it was approved as short-term (up to 14-day) monotherapy for adult patients who are hospitalized due to COVID-19 and who need breathing support from oxygen supplementation, mechanical ventilation or extracorporeal membrane oxygenation (ECMO). In addition, an emergency use authorization (EUA) allows its use, under the same conditions, to treat COVID-19 for children as young as two years old.

Imcivree Gets Additional Indication

Under Breakthrough Therapy and Priority Review pathways, the FDA approved Imcivree® (setmelanotide – Rhythm Pharmaceuticals) on June 16, 2022, to treat a rare condition known as Bardet-Biedl Syndrome (BBS). Believed to affect between 1,500 and 2,500 patients in the U.S., BBS results from mutations in some of at least 20 different genes that have been identified, so far. It causes multiple symptoms that can include cognitive difficulties, kidney problems, vision deterioration and additional fingers or toes. One of its main characteristics is hyperphagia, uncontrollable hunger that produces excessive central obesity. Imcivree, which is designated as an Orphan Drug for treating BBS, stimulates the brain’s melanocortin-4 (MC4) receptors to help reduce continual hunger signals. It also boosts the amounts of energy needed for body processes, including resting metabolism. To help control obesity for patients at least six years old who have BBS, dosing for Imcivree starts at 1mg injected subcutaneously (SC) every morning for children between six and 12 years of age and 2mg daily for older patients. If weight loss is not adequate after two weeks, doses may be adjusted to a daily maximum of 2mg for children and 3mg for teens and adults. Imcivree should be stopped for adult patients who have not lost 5% or more of their body weight and patients under 18 years of age who have not lost 5% of their body mass index (BMI) following one year of treatment. Imcivree’s initial FDA approval was in November 2020, for treating obesity due to exceptionally rare deficiencies of proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR).

New Indication for Skyrizi

On June 16, 2022, Skyrizi® (risankizumab-rzaa), an interleukin-23 (IL-23) inhibitor jointly developed by AbbVie and Boehringer Ingelheim, was FDA approved to treat adults who have active moderate to severe Crohn’s disease. Skyrizi blocks inflammation by sticking to the p19 subunit of IL-23. Stelara® (ustekinumab – Janssen), which targets IL-23 and also interleukin-12 (IL-12), is FDA approved to treat Crohn’s disease, but other IL-23 inhibitors on the U.S. market are not. For treating Crohn’s disease, the first three doses of Skyrizi are 600mg each given as one-hour or longer intravenous (IV) infusions at four-week intervals. For the fourth dose, which is four weeks after the third IV dose, the route of administration switches to an SC injection and the strength lowers to 360mg. Beginning with the fifth dose, scheduling extends to once every eight weeks. Taking about five minutes each, SC doses are delivered through prefilled cartridges that fit into a one-use auto-injector temporarily attached to the skin of the abdomen or thigh. Auto-injectors should be kept at least one foot away from cell phones and other electronic devices. Skyrizi has previous indications for adults who have psoriasis and psoriatic arthritis. Because using it may increase the risk of having infections, patients should be tested for tuberculosis (TB) before beginning treatment. In clinical studies, some patients who have Crohn’s disease experienced liver damage during the IV phase of treatment, so liver enzyme levels and bilirubin should be checked frequently for at least the first 12 weeks.

COVID-19 Vaccine Authorized for Young Children

By a unanimous vote on June 17, 2022, the members of the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), recommended revisions to allow use for children as young as six months old for the emergency use authorizations (EUAs) of Moderna’s and Pfizer/BioNTech’s COVID-19 vaccines. Several clinical trials showed that both vaccines are safe and effective for very young children. Both are given by intramuscular (IM) injections. Moderna’s are administered as a set of two doses one month apart. For children six months old through five years old, the Moderna dose is two 0.25mL doses from vials that have magenta-colored borders. Children between the ages of five years and 12 years old will receive two 0.5mL doses from Moderna vials that have purple- or teal-colored borders; and patients age 18 years and older receive 0.5mL doses from red-topped and labeled vials. For the Pfizer/BioNTech vaccine, two doses are given at a three-week interval with a third eight or more weeks after the second one for children up to five years old. Children between six months and five years old will get 0.2mL of diluted Pfizer/BioNTech solution from vials with maroon-colored tops and label borders; children five years through 11 years old will get 0.2mL from vials with orange accents; and patients at least 12 years old will get 0.3mL from vials with gray (ready to inject) or purple (needing dilution) tops and label borders. Once the Center for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) finalizes their clinical recommendations, vaccinations for young children could start as early as next week.

Generics Launched for Nexavar

Dr. Reddy’s Laboratories and Viatris (for Natco Pharma) have introduced sorafenib tablets, generics to Nexavar® (Bayer Healthcare) in the U.S. At a dose of 400mg (two tablets) two times a day, it is indicated to treat adults who have hepatocellular carcinoma (HCC) that cannot be removed by surgery, renal cell carcinoma (RCC) that has progressed, or differentiated thyroid cancer that returns or resists treatment with radioactive iodine. Pricing information currently is not available. Sales for Nexavar were estimated at nearly $70 million for calendar year 2021.

Amvuttra™ (vutrisiran)

Amvuttra™ (vutrisiran) was approved by the U.S. Food and Drug Administration (FDA) on June 13, 2022. A ribonucleic acid interference (RNAi) agent, it is approved to treat adults who have polyneuropathy (widespread peripheral nerve damage) that is caused by hereditary transthyretin-mediated (hATTR) amyloidosis. Amvuttra works by blocking (silencing) the mutated RNA responsible for hATTR, a rare disease that causes disability, pain and organ damage. It is administered by a healthcare professional as a 25mg subcutaneous (SC) injection once every three months. Alnylam Pharmaceuticals plans to introduce Amvuttra in early July through narrow network of specialty pharmacies that does not include Accredo. The estimated annual wholesale acquisition cost (WAC) is $463,500.

At a Glance

• Brand (Generic) Name: Amvuttra™ (vutrisiran)
• Manufacturer: Alnylam Pharmaceuticals
• Date Approved: June 13, 2022
• Indication: to treat adults who have polyneuropathy caused by hATTR
• Dosage Forms Available: prefilled, single-dose syringes containing 25mg of Amvuttra in 0.5mL of solution for subcutaneous injection
• Launch Date: early July 2022
• Estimated Annual Cost: $463,500 (WAC)
• Only about one in 100,000 Americans – approximately 3,000 individuals — are believed to have polyneuropathy caused by hATTR.
• Ordinarily, RNA transfers specific amino acid sequences from genes into cells that then produce the specified proteins. However, when some of the sequences mutate, abnormal disease-causing proteins sometimes are made.
• The proteins that cause hATTR amyloidosis are folded and bent in ways the body cannot use, so they build up – mostly in the heart and nerve fibers in the body’s periphery. Known as amyloid fibrils, they cause numbness and pain in the hands, arms, legs and feet. Eventually, they interfere with organ function, leading to death.
• RNA interference (RNAi) uses short bits of synthetic RNA that block the defective mRNA. By interrupting RNA that carries damaged sequences for hATTR amyloidosis, Amvuttra stops (silences) the resulting proteins.
• Results from the phase III HELIOS-A clinical trial showed that scores on a standardized neuropathy impairment test improved by an average of 2.2 points for patients treated with Amvuttra as compared to a loss of nearly 15 points for patients who received a placebo in a previous study. Treated patients also reported better quality of life and better walking ability.
• In the study, 11% of patients experienced joint pain and 7% had breathing difficulties after using Amvuttra.
• Because using Amvuttra reduces the body’s stores of vitamin A, patients using it should take a vitamin A supplement. They also should be aware of the symptoms, such as a reduced ability to see well in poorly lit areas, of vitamin A deficiency.
• Alnylam’s Onpattro® (patisiran) was approved by the FDA in August 2018 for treating hATTR polyneuropathy. It is administered by intravenous (IV) infusion once every three weeks. To minimize side effects, patients need to be treated with acetaminophen, a corticosteroid, an H1 blocker (such as diphenhydramine) and an H2 blocker (such as famotidine) before receiving Onpattro infusions.
• Two months later, a second hATTR drug, Tegsedi® (inotersen – Akcea Therapeutics) also was FDA approved. An antisense oligonucleotide that prevents the formation of amyloid fibrils, it is given in weekly SC injections. Tegsedi has boxed warnings and a risk evaluation and mitigation strategy (REMS) because it may cause thrombocytopenia (possibly sudden and dangerous drops in platelet count) and/or glomerulonephritis (kidney inflammation that may cause kidney failure).
• The annual wholesale acquisition cost (WAC) for either Onpattro or Tegsedi is approximately $450,000.
• Amvuttra has Orphan Drug status for treating ATTR amyloidosis.