The U.S. Food and Drug Administration's Center for Drug Evaluation and Research approved 48 first-of-their-kind therapies in 2019, the second-highest number of new molecular entities cleared for the world's largest pharmaceutical market in the past two decades.
The agency set the record in 2018, with 59 new molecular entities approved by the FDA's Center for Drug Evaluation and Research, or CDER.
Many of the novel drugs cleared in 2019 are expected to change the trajectory of the diseases they were approved to treat, though a number of them come at a high cost.
Most of the 2019 approvals occurred under the oversight of acting FDA commissioners — first Ned Sharpless and later Brett Giroir — after Scott Gottlieb left the agency less than two years into the job.
Gottlieb's replacement, Stephen Hahn, was sworn in as commissioner Dec. 17, 2019, just in time to oversee the last few approvals of the year.
Health and Human Services Secretary Alex Azar swearing in Stephen Hahn as U.S. Food and Drug Administration commissioner on Dec. 17, 2019.
Among the notable 2019 approvals by FDA's CDER was Vertex Pharmaceuticals Inc.'s Trikafta, the first triple combination therapy for patients 12 years or older with the most common genetic mutation found in cystic fibrosis patients, known as F508del.
Cystic fibrosis is a rare, progressive, life-threatening disease that results in the formation of thick mucus that builds up in the lungs, digestive tract and other parts of the body. About 90% of patients with cystic fibrosis have the F508del mutation.
Vertex priced Trikafta at $311,503 annually, or $23,896 per 28-day pack.
Also approved in 2019 was Global Blood Therapeutics Inc.'s Oxbryta, the first medicine that specifically targets the root cause of sickle cell disease, an inherited blood disorder that can cause anemia, pain and damage to the lungs, kidneys, spleen and brain.
The company, however, must conduct additional studies to verify Oxbryta's clinical benefit, the FDA noted.
Oxbryta was priced at $125,000 per year, or about $10,400 per month.
The U.S. regulator also cleared Novartis AG's Adakveo as the first targeted therapy to reduce the frequency of vaso-occlusive crisis, a common and painful complication of sickle cell disease.
Adakveo costs between $84,000 and $114,000 per year.
Novartis had other notable approvals in 2019 from FDA's CDER, including the company's breast cancer drug Piqray, its wet age-related macular degeneration treatment Beovu and its multiple sclerosis medicine Mayzent.
More than a half a dozen of the novel drugs approved by the FDA in 2019 gained those clearances months ahead of the agency's expected action date, including Vertex's Trikafta, Global Blood's Oxbryta and Novartis' Adakveo.
Other new products that won early approvals last year were AstraZeneca PLC's metastatic breast cancer medicine Enhertu, Seattle Genetics Inc.'s and Astellas Pharma Inc.'s bladder cancer therapy Padcev, Alnylam Pharmaceuticals Inc.'s acute hepatic porphyria drug Givlaari, and BeiGene Ltd.'s mantle cell lymphoma treatment Brukinsa.
Rare disease drugs
U.S. regulators also granted a number of orphan drug approvals, a designation created by Congress in 1983 to provide incentives, like added market exclusivity and tax breaks, to entice biopharmaceutical companies to develop medicines for rare diseases and conditions, which affect about 30 million Americans.
Among those new orphan drugs was Sarepta Therapeutics Inc.'s Vyondys 53 for Duchenne muscular dystrophy. DMD is a rare, debilitating, progressive and ultimately fatal childhood genetic disease caused by mutations in the gene encoding dystrophin, a protein that plays a key role in maintaining muscle integrity.
Vyondys 53 is intended for use in about 8% of the DMD population.
The FDA initially rejected Vyondys 53 in August 2019, a decision Sarepta disputed. The agency granted the company's appeal, and Sarepta quietly resubmitted its application.
But keeping Vyondys 53 on the U.S. market is contingent on the success of a confirmatory trial, the FDA and Sarepta both said.
New biological therapies
The FDA's Center for Biologics Evaluation and Research, or CBER, also granted a number of notable approvals in 2019 to novel products, including Novartis' gene therapy Zolgensma in children less than 2 years old with spinal muscular atrophy.
The rare disease is caused by a mutation in the SMN1 gene, which carries instructions for making the survival motor neuron protein.
Zolgensma is an adeno-associated virus vector-based gene therapy. The vector delivers a fully functional copy of the human SMN1 gene into the target motor neuron cells.
Zolgensma is the most expensive medicine in the world, with a list price of $2.1 million.
Novartis obtained Zolgensma through its $8.7 billion acquisition of AveXis Inc. in 2018. Both companies came under investigation by the FDA and Congress over concerns Zolgensma's U.S. marketing application contained manipulated preclinical animal data.
The FDA's CBER also cleared Sanofi's Dengvaxia in 2019 as the first vaccine to prevent dengue, the most common mosquito-borne viral disease in the world.
Record biosimilar approvals
In 2019, the FDA also granted approval to 10 lower-cost versions of biologic therapies, or biosimilars — the most in one year.
Congress gave the FDA the authority to approve biosimilars under the Biologics Price Competition and Innovation Act, which was adopted in 2010 as part of the Affordable Care Act.
But it took the agency five years before it approved its first biosimilar in 2015. Since then, the agency has cleared a total of 26 biosimilars, lagging far behind Europe, where over 50 of the products have been authorized for marketing.
First-time generic medicines
Also in 2019, the FDA approved nearly 100 first-time generics — the first copycats of innovator small-molecule pills, which are easier to replicate than large-molecule biologic medicines.
"These approvals are yet another example of FDA's commitment to fostering generic drug competition, which can improve access to lower-cost, safe and high-quality medicines," Hahn tweeted Dec. 23, 2019.
Regulators acknowledged, however, that those approvals do not necessarily mean those products will be immediately marketed.
One of the most recent first generics approved by the FDA was the blood thinner apixaban. Bristol-Myers Squibb Co. markets the branded version under the name Eliquis.
In a recent filing with the U.S. Securities and Exchange Commission, Bristol-Myers noted that 25 generic companies had filed applications with the FDA in 2017 seeking approval of generic versions of Eliquis and two patents on the drug were challenged.
Bristol-Myers and its partner Pfizer Inc. initiated patent lawsuits against the generic filers in federal district courts in Delaware and West Virginia. In August 2017, the U.S. Patent and Trademark Office granted patent term restoration to the Eliquis composition of matter patent, restoring the term from February 2023 to November 2026.
While Bristol-Myers said it had settled lawsuits with a number of generic filers through September 2019, it said those agreements do not affect the exclusivity protection on Eliquis that covers the product until 2026.
The FDA has yet to report the total number of all generic drug application approvals for 2019.