The U.S. Food and Drug Administration broke a number of records in 2018, most notably, shattering the agency's all-time high in approving first-of-their-kind therapies — clearing 59 last year.
The previous record was held in 1996, when the FDA's Center for Drug Evaluation and Research permitted 53 new molecular entities, or NMEs, to enter the U.S. market.
The 2018 approvals far surpassed the 46 NMEs the FDA cleared in 2017.
Regulators rushed to approve two new drugs before the agency got caught in partial government shutdown at midnight on Dec. 22, 2018 — a closure, now into its second week, that resulted from a funding dispute between Congress and the White House.
The two drugs — Alexion Pharmaceuticals Inc.'s Ultomiris and Stemline Therapeutics Inc.'s Elzonris — were approved to treat two rare blood diseases.
A banner year for rare disease drugs
Ultomiris and Elzonris both were deemed orphan drugs, a designation created 35 years ago 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.
In all, the FDA approved 34 rare disease drugs in 2018 — the first time ever those products made up the majority of NMEs cleared by the agency in one calendar year.
The Orphan Drug Act, passed in 1983, defines a rare disease or condition as one that affects fewer than 200,000 people in the U.S.
Manufacturers granted the FDA orphan designation used to be able to claim a tax credit of up to 50% of qualified clinical testing expenses for medicines. But lawmakers cut that in half, permitting drugmakers to now claim only 25% — a change made under the Republicans' Tax Cuts and Jobs Act, signed into law in December 2017.
A group of Republicans had tried nixing the orphan drug tax credit altogether, but that effort did not succeed.
For now, development for rare disease medicines remains strong.
The 2018 orphan drug approvals, however, did not come without some controversy.
After Catalyst Pharmaceuticals Inc. won approval late last year for Firdapse as a treatment for Lambert-Eaton myasthenic syndrome, or LEMS, a rare neuromuscular disease, the company sparked a firestorm when it priced the medicine at $375,000 per year.
Compounding pharmacies had been making another version of the product with the same active ingredient for a number of years and selling it for about $500 per year.
Jacobus Pharmaceutical Co. Inc. also has provided its own experimental version of the medicine for more than two decades free of charge to LEMS patients under the FDA's expanded-access program, also known as compassionate use.
The FDA's orphan drug program has also recently come under scrutiny by Congress, which had its watchdog, the U.S. Government Accountability Office, investigate whether some drugmakers were taking advantage of the designation to extend the market protection of their products.
In November 2018, the GAO reported that the FDA's drug reviewers had often failed to ensure the medicines granted the orphan drug designation met the necessary requirements for the status.
The medicines cleared by U.S. regulators in 2018 came from a unique blend of therapeutic areas, said Khushboo Sharma, the acting chief of staff in the FDA's Office of New Drugs.
Among the diseases the FDA approved new medicines for were cystic fibrosis, HIV infection, plaque psoriasis, chronic idiopathic constipation, rheumatoid arthritis, complicated urinary tract infections, endometriosis, chronic obstructive pulmonary disease, travelers' diarrhea, malaria and influenza, Sharma noted at a Dec. 11, 2018, forum in Washington.
The agency permitted 17 new oncology products to enter the market in 2018 — an area of medicine that has been particularly strong in recent years for new drug approvals, specifically for targeted therapies.
The FDA also approved three novel products to treat migraine headaches: Eli Lilly and Co.'s Emgality, Teva Pharmaceutical Industries Ltd.'s Ajovy and Amgen Inc.'s and Novartis AG's Aimovig.
In addition, regulators cleared the first medicine for the U.S. market that contains a purified drug substance derived from marijuana — GW Pharmaceuticals PLC's Epidiolex. The drug was approved to treat seizures associated with Lennox-Gastaut and Dravet syndromes, two rare and severe forms of epilepsy.
The FDA also gave its nod last year to US WorldMeds LLC's Lucemyra, the first non-opioid treatment used to manage opioid withdrawal symptoms in adults.
SIGA Technologies Inc. also won approval to market Tpoxx as the first treatment in the U.S. for smallpox, a highly contagious disease. Smallpox was declared eradicated in 1980, but health officials have raised concerns the disease could re-emerge as a bioterrorism agent.
Biosimilars and generic
The FDA also broke records in 2018 for approvals of generic drugs and lower-cost versions of biologic therapies, or biosimilars.
While FDA Commissioner Scott Gottlieb noted in a Dec. 31, 2018, tweet that the calendar year totals for generic medicines were pending, the agency's data showed that by the end of November, regulators had cleared 741 of those lower-cost small molecules and tentatively approved 180, for a total of 921.
After the December approvals are added, the FDA is expected to break its 2017 record of 1,027 generic drugs cleared in one year.
The agency beat its previous fiscal year record for generic drugs, with 971 of those products receiving final or tentative approval by Sept. 30, 2018.
As of Nov. 30, 2018, there were 95 first-time generics approved during the calendar year, according to the FDA's most recent data.
In 2018, the FDA also granted approval to seven biosimilars — the most in one year.
Since 2015, the regulator has cleared a total of 16 biosimilars, a market that has been somewhat slow to catch on in the U.S.
Gottlieb has vowed to stop brand-name drugmakers from using gaming tactics aimed at thwarting biosimilar competition. Those maneuvers by innovator companies have left the struggling biosimilars market "anemic," possibly costing Americans billions of dollars, the commissioner said.