FDA Approval Surge

During October and November 2019, we saw the FDA approve thirteen new investigational drugs. Five of these drugs have annual costs in excess of $100,000. Each of these potential budget busters was approved months ahead of their PDUFA Dates, targeting such indications as the most common cystic fibrosis mutation, mantle cell lymphoma for patients who have received at least one prior therapy, sickle cell disease, partial-onset seizures in adults, and complicated urinary tract infections.

Here’s a link to a relevant article about the five budget busters from the November 27th ENDPOINTS News about approval process, Congress’ viewpoint and what FDA is analyzing https://endpts.com/fda-approves-5-new-costly-drugs-well-ahead-of-pdufa-dates/

Thirteen October and November Approvals

1. The FDA approved trifarotene cream (Aklief, Galderma) on October 4 for the treatment of acne vulgaris.
2. The FDA approved lasmiditan (Reyvow, Lilly) on 10/11/2019 for the treatment of acute migraines, with or without aura, in adult patients. Due to the occurrence of dizziness and sedation from CNS depression, patients are warned of potential impairment while taking lasmiditan and advised not to drive, operate machinery or take with alcohol or other CNS depressants for at least eight hours after taking the drug, even if they feel well enough to do so. The FDA announced that during clinical trials the most common ADR with lasmiditan were dizziness, fatigue, paresthesia and sedation.
3. The FDA approved brolucizumab (Beovu, Novartis) on 10/8/2019 for the treatment of wet age-related macular degeneration (AMD). Brolucizumab is administered by intravitreal injection every three months. WAC was set at $1,850 per dose, the same as aflibercept (Eylea), which is dosed more frequently. After the loading dose, analysts estimate the annual brolucizumab WAC at $16,000 for both eyes compared to $24,000 for aflibercept and and $40,000 for ranibizumab (Lucentis).
4. The FDA approved afamelanotide (Scenesse, Clinuvel) on 10/8/2019 to treat phototoxic reactions in patients with erythropoietic protoporphyria.
5. The FDA approved the combination of elexacaftor, ivacaftor, and tezacaftor (Trikafta, Vertex Pharmaceuticals) on October 21 for the treatment of patients age 12 years or older with cystic fibrosis (CF) and at least one F508del mutation in the CF transmembrane conductance regulator (CFTR) gene. The combination was approved almost 6 months early (3/19/2020 PDUFA date).
6. The FDA approved diroximel fumarate (Vumerity, Biogen/Alkermes) on 10/30/2019 for the treatment of relapsing forms of multiple sclerosis. Diroximel fumarate is an oral prodrug of monomethyl fumarate, which allows the 505(b)(2) pathway based on Biogen’s dimethyl fumarate (Tecfidera) to be used. Biogen is licensing diroximel fumarate from Alkermes.
7. The FDA approved luspatercept (Reblozyl, Celgene, Acceleron) on 11/8/2019 for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell transfusions.
8. The FDA approved cefiderocol (Fetroja, Shionogi) on 11/15/2019 for the treatment of adult patients with complicated urinary tract infections (cUTI), including kidney infections caused by susceptible Gram-negative microorganisms, who have limited or no alternative treatment options. The package insert for cefiderocol will include a warning regarding higher all-cause mortality rate observed in cefiderocol-treated patients compared to those treated with other antibiotics in a trial in critically ill patients with multidrug-resistant Gram-negative bacterial infections.
9. The FDA approved crizanlizumab (Adakveo, Novartis) on 11/15/2019 to reduce the frequency of vaso-occlusive crisis in patients aged 16 years or older with sickle cell disease. WAC for crizanlizumab is $2,357 per vial. With an average dose of three to four vials per month, WAC would be $7,071, or $9,428, per month.
10. The FDA approved zanubrutinib (Brukinsa, BeiGene) on 11/13/2019 for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy. WAC for a 30-day supply of zanubrutinib has been set at $12,935.
11. The FDA approved givosiran (Givlaari, Alnylam) on 11/20/2019 for the treatment of adults with acute hepatic porphyria. WAC for givosiran is $39,000 per vial with an estimated annual cost after discount of $442,000.
12. The FDA approved cenobamate (Xcopri, SK Life Science) on 11/21/2019 for the treatment of partial-onset seizures in adult patients with epilepsy. The FDA reports the most common ADR in the trials were somnolence, dizziness, fatigue, and diplopia. Cenobamate may cause a reduction in the QT interval > 20 milliseconds, so the FDA advises avoiding the drug in patients with Familial Short QT syndrome.
13. The FDA approved voxelotor (Oxbryta, Global Blood Therapeutics) on 11/25/2019 for the treatment of sickle cell disease in patients 12 years and older. The drug had a PDUFA Date of 2/26/2020 and the FDA gave voxelotor Orphan Drug, Fast Track and Breakthrough Therapy Priority Designations.

ICER’s Review of Migraine Medications

ICER released a draft review of lasmiditan, ubrogepant and rimegepant in November 2019. ICER found the drugs to be comparable to each other in efficacy, but not as efficacious as triptans. Lasmiditan, ubrogepant and rimegepant would provide a benefit for patients with cardiovascular disease that have a contraindication to triptans, were not helped by triptans or do not tolerate them. Since triptans are available as generics, ICER concludes that triptans would provide a greater benefit at a lower cost than lasmiditan, ubrogepant or rimegepant. To reach a threshold of $150,000 per quality-adjusted life year ICER estimated an annual cost of $1,850 for lasmiditan, $1,780 for rimegepant and $1,740 for ubrogepant.