Monthly News Roundup - June 2024

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on June 30, 2024.

FDA Grants Expanded Approval to Skyrizi for Ulcerative Colitis

On June 18th, the U.S. Food and Drug Administration (FDA) approved AbbVie’s Skyrizi (risankizumab-rzaa) for adults with moderately to severely active ulcerative colitis (UC). Skyrizi is also approved to treat adults with plaque psoriasis, psoriatic arthritis, and Crohn’s disease.

Ulcerative colitis is a form of inflammatory bowel disease that causes inflammation in the digestive tract and can result in damage to the colon lining. Symptoms can include abdominal pain, bloody stool and fecal urgency and incontinence.

Skyrizi is an interleukin-23 (IL-23) inhibitor that selectively blocks IL-23 to lower inflammation and associated symptoms in UC.

The Skyrizi induction dosage is via intravenous (IV) infusion at Week 0, Week 4, and Week 8. Maintenance dosage is given via subcutaneous (under the skin) injection at Week 12, then every 8 weeks thereafter.

Following the starter doses, Skyrizi treatment can be maintained at home using an on-body injector (OBI) or by prefilled syringe. The OBI injection dose is delivered in about 5 minutes.

Approval was based on induction and maintenance placebo-controlled studies in patients with moderately to severely active ulcerative colitis. In clinical trials, Skyrizi helped patients achieve remission at 12 weeks and one year. In the induction trial (1,200 mg starter IV infusion), Skyrizi led to visible colon lining repair in 36% of patients at 12 weeks (vs. 12% placebo). During the maintenance phase (180 mg subcutaneous maintenance injection), 51% of patients achieved visible colon lining repair at one year (vs. 31% placebo group).

The most common side effects seen in UC studies were arthralgia (joint pain) during induction, and arthralgia, fever, injection site reactions and rash during maintenance treatment.

Ohtuvayre: A First-in-Class PDE3 / PDE4 Inhibitor for COPD Maintenance

Ohtuvayre (ensifentrine) was approved in June for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adults. Ohtuvayre is the first inhaled COPD maintenance product with a novel mechanism of action in more than 20 years. It is only for use with a nebulizer after patient training.

Ohtuvayre is a small molecule classified as a dual inhibitor of phosphodiesterase 3 and 4 (PDE3 and PDE4) enzymes and combines bronchodilator and non-steroidal anti-inflammatory effects.

The recommended dose is 3 mg (one ampule) twice daily administered by oral inhalation using a standard jet nebulizer with a mouthpiece.

Approval included data from the Phase 3, placebo-controlled ENHANCE trials (n=1,553) with a primary endpoint of change from baseline in FEV1 AUC0-12h post dose at Week 12. FEV1 is a common lung function test that measures how much air you can expel over one second following maximal inhalation. Ohtuvayre met the primary endpoint in both ENHANCE-1 and ENHANCE-2, demonstrating significant and clinically meaningful improvements in lung function.

Warnings and precautions include risk of paradoxical bronchospasm (sudden breathing problems) and an increase in psychiatric adverse reactions, including suicidality. Ohtuvayre is not used for acute (sudden) COPD symptoms. Always have a rescue inhaler with you.

Most common adverse reactions (incidence ≥ 1% and more common than placebo) include back pain, hypertension (high blood pressure), bladder infection, and diarrhea.

Ohtuvayre is manufactured by Verona Pharma and is expected to launch in the 3rd quarter of 2024.

Rytelo Approved for Lower-Risk Myelodysplastic Syndromes (MDS) with Anemia

In June, the FDA approved Geron Corporation’s Rytelo (imetelstat) infusion to treat adults with low to intermediate-1 risk myelodysplastic syndromes (MDS) with anemia. Eligible patients have not responded to, have stopped responding, or cannot be treated with erythropoiesis-stimulating agents (ESA).

Myelodysplastic syndromes are a group of cancers in which red blood cells do not mature and become healthy, leading to anemia and the need for ongoing blood transfusions. Symptoms may include weakness, fatigue, shortness of breath, infections, bruising and easy bleeding.

Rytelo, an oligonucleotide telomerase inhibitor, works by binding to and inhibiting the activity of the telomerase enzyme which selectively kills the malignant stem and progenitor cells in the bone marrow.

The recommended dosage of Rytelo is 7.1 mg / kg administered as an intravenous (IV) infusion over 2 hours every 4 weeks. Premedicate prior to dosing for potential infusion-related reactions

Approval was based on the IMerge Phase 3 clinical trial, showing Rytelo demonstrated significantly higher rates of red blood cell transfusion independence (RBC-TI) vs. placebo for at least 8 consecutive weeks (Rytelo 39.8% vs. placebo 15%) and for at least 24 weeks (Rytelo 28% vs. placebo 3.3%). Median RBC-TI duration was durable and sustained for up to 1.5 years (24-week responders) and 1 year (8 weeks responders).

Warnings and precautions include thrombocytopenia, neutropenia, infusion reactions, and potential risk to a fetus.

The most common side effects include: decreased platelets, decreased white blood cells, increased AST or ALT (liver enzymes), increased alkaline phosphatase, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia (joint/muscle pain), COVID-19 infections, and headache.

Elevidys Label Broadened for Treatment of Duchenne Muscular Dystrophy

In June, Sarepta Therapeutics announced the approval of Elevidys (delandistrogene moxeparvovec-rokl) for the treatment of patients at least 4 years of age with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. The FDA granted traditional approval for DMD ambulatory patients and accelerated approval for non-ambulatory patients.

DMD is a genetic disease caused by a mutation in the DMD gene that encodes instructions for a protein called dystrophin that keeps muscle cells intact. DMD primarily affects males starting in early childhood, often between the ages of 2 and 3. In addition to progressive weakness and loss of skeletal and heart muscles, it can lead to premature death in the second or third decade of life due to heart problems and lung failure.

Elevidys is an adeno-associated virus vector-based gene therapy given as a one-time, single-dose gene transfer therapy. It is designed to treat the underlying cause of DMD by delivering a functional shortened dystrophin protein into the muscle tissue.

Elevidys is given as an intravenous (IV) infusion over 1-2 hours. It should not be used in patients with any deletion in exon 8 and/or exon 9 in the DMD gene.

Warnings and precautions include infusion-related reactions, acute serious liver injury, immune-mediated myositis (muscle inflammation) and myocarditis (heart muscle inflammation).

Common adverse reactions include vomiting and nausea, liver injury, pyrexia (fever), and thrombocytopenia (low platelet counts).

Continued approval for non-ambulatory patients may depend upon outcomes seen in further clinical studies.

FDA Clears Capvaxive: Merck’s 21-Valent Pneumococcal Vaccine

This past month the FDA approved Merck’s Capvaxive (pneumococcal 21-valent conjugate vaccine), a 21-valent pneumococcal conjugate vaccine indicated in adults 18 years of age and older for active immunization to prevent invasive disease and pneumonia caused Streptococcus pneumoniae serotypes. Capvaxive contains eight unique serotypes.

Pneumococcal disease is an infection caused by a bacteria called Streptococcus pneumoniae. There are over 100 different serotypes of pneumococcal bacteria, with some serotypes putting people at risk for invasive pneumococcal illnesses, such as bacteremia (bloodstream infection), bacteremic pneumonia (pneumonia with bacteremia), meningitis (infection of the coverings of the brain and spinal cord), as well as non-invasive pneumococcal pneumonia (bacterial lung infection).

Capvaxive is given as a single dose administered by intramuscular injection.

Capvaxive includes eight unique serotypes (5A, 15C, 16F, 23A, 23B, 24F, 31 and 35B) not covered by currently approved pneumococcal vaccines. These serotypes were responsible for approximately 27% of invasive pneumococcal disease cases in adults 50 years of age and older and approximately 30% in adults 65 years of age and older.

The use for prevention of pneumonia is approved under accelerated approval and continued approval may depend upon verification of clinical benefit in additional studies.

Common side effects include injection-site pain, fatigue, headache, muscle aches, and injection-site redness or swelling.

FDA Approves Genentech’s PiaSky to Treat Paroxysmal Nocturnal Hemoglobinuria

The FDA has approved Genentech’s PiaSky (crovalimab-akkz) for the treatment of adult and pediatric patients 13 years and older with paroxysmal nocturnal hemoglobinuria (PNH) who weigh at least 40 kg (88 lb). PiaSky allows the option to self-administer a subcutaneous (under the skin) injection every 4 weeks after initial intravenous loading doses.

Paroxysmal nocturnal hemoglobinuria is a rare and life-threatening blood condition in which red blood cells are destroyed by the body’s immune system causing anemia, fatigue, blood clots, and possible kidney disease.

PiaSky (crovalimab-akkz) is a complement C5 inhibitor and works in PNH by blocking part of the complement (immune) system cascade.

It is given as a single loading dose by intravenous (IV) infusion on Day 1, followed by four additional weekly loading doses administered by subcutaneous injection on Days 2, 8, 15, and 22. Maintenance dosing starts on Day 29 and is administered every 4 weeks by subcutaneous injection.

In the Phase III, 24-week COMMODORE 2 study (n=204), PiaSky was found to be non-inferior to eculizumab (Soliris) in both co-primary efficacy endpoints of hemolysis control and transfusion avoidance as well as in the secondary efficacy endpoints of BTH (breakthrough hemolysis) and hemoglobin (Hb) stabilization. It had a comparable safety profile as well.

PiaSky carries a Boxed Warning for an increased risk of serious and life-threatening infections caused by Neisseria meningitidis. It is only available through a restricted program called the PiaSky REMS. Meningococcal infections may quickly become life-threatening or cause death if not recognized and treated early.

Warnings and precautions for this drug include Type III hypersensitivity reactions in patients switching from another C5 inhibitor (may cause inflammation and tissue damage), an increased susceptibility to serious infections, and infusion and injection-related reactions.

Common adverse reactions (incidence ≥10%) were infusion-related reactions, respiratory tract infections (including infections of the lungs, cold symptoms, and pain or swelling of the nose or throat), viral infection, and Type III hypersensitivity reactions.

Wakix Use Expanded to Children 6 Years and Older with Narcolepsy

Harmony Biosciences announced the approval of once-daily oral Wakix (pitolisant), a histamine-3 (H₃) receptor antagonist / inverse agonist for the treatment of excessive daytime sleepiness (EDS) in children 6 years of age and older with narcolepsy.

Narcolepsy is characterized by immense daytime drowsiness and sudden attacks of sleep. It is also approved to treat excessive daytime sleepiness (EDS) or cataplexy (sudden loss of muscle strength) in adults with narcolepsy.

Wakix works by increasing the synthesis and release of histamine, a wake-promoting neurotransmitter in the brain. It is not a controlled substance.

The recommended dose is given orally once daily in the morning when you first wake up. Initially, doses are increased over a 3-week period based on clinical response and tolerability.

Approval was based on a study with 110 pediatric patients 6 to 17 years who were randomized to receive Wakix or placebo. Results demonstrated statistically significantly greater improvement in final PDSS (Pediatric Daytime Sleepiness Score) total score compared to placebo, of -3.41 points (95% CI: -5.52, -1.31).

Wakix is contraindicated in severe hepatic (liver) impairment. Warnings and precautions include increases in QT interval (which may lead to a serious abnormal heart rhythm).

The most common adverse reactions (≥5% and greater than placebo) in children 6 years and older were headache and insomnia (trouble sleeping).

Iqirvo Granted Accelerated Approval to Treat Primary Biliary Cholangitis

The FDA has granted accelerated approval to Iqirvo (elafibranor) to treat adult Primary Biliary Cholangitis (PBC), a rare and chronic liver disease that originates in the small bile ducts. It is used as combination therapy in adults who have an inadequate response to ursodeoxycholic acid (UDCA), or as a single treatment in patients unable to tolerate UDCA.

Primary biliary cholangitis (PBC) is a rare and chronic autoimmune liver disease that originates in the small bile ducts. It leads to a build-up of bile and toxins (cholestasis) leading to liver scarring and bile duct destruction. Symptoms include fatigue and itching, which may be severe and can lead to liver failure, liver transplant or death.

Iqirvo is a dual peroxisome-activated receptor (PPAR) alpha / delta (α,δ) agonist that works by activating PPAR receptors to block the production of bile acids, although the exact mechanism is not known.

The recommended dosage is 80 mg orally once daily with or without food.

Iqirvo received accelerated approval based on data from the Phase III ELATIVE trial and the reduction of the biochemical marker alkaline phosphatase (ALP). Iqirvo plus UDCA (n=108) achieved a 51% response vs. versus 4% in the placebo plus UDCA group. Most patients (95%) received study treatment (Iqirvo or placebo) in combination with UDCA.

Warnings and precautions include myalgia, myopathy, and rhabdomyolysis, fractures, fetal harm, drug-induced liver injury, severe allergic reaction and biliary obstruction. Limitation of use: Iqirvo is not recommended for people with symptoms or signs of advanced liver disease (decompensated cirrhosis).

Side effects in at least 5% of patients include weight gain, diarrhea, stomach pain, nausea, vomiting, joint pain, constipation, muscle injury,

It is not known if Iqirvo use will improve a patient’s chance of survival or prevent liver decompensation. Continued approval may depend on further studies showing a positive clinical benefit.

Iqirvo is manufactured by Ipsen Biopharmaceuticals.

FDA Approves Vigafyde, the First Ready-to-Use Vigabatrin Oral Solution

This past month the FDA cleared Vigafyde (vigabatrin), a ready-to-use oral solution of the approved anti-seizure medicine vigabatrin. Vigafyde is indicated as monotherapy for the treatment of infantile spasms in pediatric patients 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss.

Infantile spasms are a rare, severe form of epilepsy that can progress to long-term permanent issues such as continued seizures, other forms of epilepsy, autism spectrum disorder, and developmental issues. It typically begins in children under one year of age.

Vigafyde works by inhibiting the enzyme GABA transaminase which increases gamma-aminobutyric acid (GABA) levels in the brain. Elevations in GABA are thought to enhance seizure control by modulating neuronal excitability.

Vigafyde is given as an oral dose twice daily based on weight and does not require additional reconstitution or dilution prior to administration. Vigafyde (100 mg/mL) is more concentrated than vigabatrin solutions that are prepared from powder (50 mg/mL).

Vigafyde carries a Boxed Warning for permanent vision loss and monitoring of vision. It is only available through a restricted program called the Vigabatrin REMS.

Warnings and precautions associated with Vigafyde include abnormal MRI signal changes and intramyelinic edema, withdrawal seizures, and anemia. Common adverse reactions include somnolence, bronchitis, ear infection, and acute otitis media.

Vigafyde is manufactured by Pyros Pharmaceuticals, Inc. and expected to be available in the second half of 2024.

FDA Approves Sofdra Topical Underarm Gel for Excessive Sweating

In June, the FDA approved Sofdra (sofpironium 12.45%), a topical anticholinergic gel indicated for the treatment of primary axillary hyperhidrosis (excessive underarm sweating) in adults and children 9 years of age and older. It is applied directly to the underarm area.

Hyperhidrosis is a medical condition that leads to excessive underarm sweating. It can be a disabling and embarrassing condition, which may lower a patient’s quality of life. About 10 million patients in the U.S. have primary axillary hyperhidrosis.

Acetylcholine release stimulates sweat production. Sofpironium, the active ingredient in Sofdra, blocks acetylcholine receptors found in the eccrine sweat glands to reduce the rate of sweating.

Sofdra gel is administered topically to each underarm area once a day at bedtime.

Approval was based on the results of the Phase III CARDIGAN studies in 701 patients. Sofdra vs. vehicle treatment successfully met all endpoints with meaningful changes from baseline in Gravimetric Sweat Production (GSP) and the Hyperhidrosis Disease Severity Measure-Axillary, 7-item (HDSM-AX7) score.

Sofdra should not be used (is contraindicated) in medical conditions that can be worsened by the anticholinergic properties (like glaucoma, paralytic ileus, severe ulcerative colitis, myasthenia gravis, Sjogren’s syndrome and others).

Warnings and precautions include use in urinary retention, impaired control of body temperature in hot environments, and blurred vision. Common side effects include dry mouth, vision blurred, application site pain or redness, mydriasis (pupil dilation), application site dermatitis, application site itching and irritation, urinary retention