It looks like drug approvals have well and truly bounced back. 2019’s total of 45 approvals may not have hit the record high posted in 2018, but it fits into a general upward trend since 2016, when the FDA approved just 22 drugs.
“A ten year view of novel drug approvals in the US shows how numbers have climbed recently. The sector’s focus on rare diseases or poorly served niches in the oncology world has a lot to do with this focus, which the FDA has rewarded with very fast decisions,” wrote Vantage in its 2020 Preview.
By the FDA’s count, it approved 48 new molecular entities, down from 59 the year before and 46 in 2017. As has become custom, our count is different. We included Zolgensma, Novartis’ gene therapy for spinal muscular atrophy, and Ervebo, Merck’s Ebola vaccine. We omitted a handful of drugs, such as a dye used in eye surgery and a trio of diagnostic imaging agents. We also left out Accrufer, an iron replacement in the form of ferric maltol.
Novartis emerged the clear winner in 2019. Counting Zolgensma, the Big Pharma tallied six new drug approvals. And unlike Pfizer, which won the most approvals in 2018 with four cancer nods, Novartis' approvals spanned multiple disease areas: breast cancer drug Piqray; multiple sclerosis drug Mayzent; sickle cell treatment Adakveo; Beovu, for wet age-related macular degeneration; and Egaten, a drug approved long ago to treat parasites in animals that got its first FDA nod in February to treat people with liver flukes.
For the most part, other companies big and small bagged one approval each. A handful, including Roche, Merck, Daiichi Sankyo and AbbVie, picked up two approvals apiece, but the winner in that group was Bristol-Myers Squibb, which ended a two-year drought. Its $74 billion buyout of Celgene is delivering results. Both of BMS’ nods in 2019 were for hematology assets picked up in that deal: myelofibrosis drug Inrebic and Reblozyl, which treats anemia in patients with beta thalassemia.
Speaking of Bristol-Myers, the only top 15 pharma company to go without a new drug approval in 2017 and 2018, the number of have-nots multiplied this year: GlaxoSmithKline, Gilead, and Teva. AstraZeneca would have joined them if not for an 11th-hour approval of its Daiichi-partnered breast cancer drug Enhertu.
A drug for Duchenne muscular dystrophy took the crown for most controversial approval for the third time. The FDA’s surprise approval of Sarepta’s Vyondys 53—a drug it had rejected four months earlier—followed that of Sarepta’s Exondys 51 in 2016 and the 2017 nod for Marathon Pharma’s Emflaza, which came to market with an $89,000-per-year price tag despite being available overseas for decades at a much lower price.
As usual, cancer approvals led the pack at 11 nods, with solid tumor drugs outnumbering blood cancer medications 7-4. Johnson & Johnson’s lone approval, Balversa, became the first targeted treatment for bladder cancer, and Seattle Genetics and Astellas scored an early nod for Padcev, an antibody-drug conjugate for metastatic bladder cancer. Roche’s Rozlytrek joined Bayer and Loxo’s—now Eli Lilly’s—Vitrakvi as a “tissue-agnostic” drug. It is approved to treat tumors with an NTRK gene fusion, the same indication as Vitrakvi, as well as ROS1-positive non-small cell lung cancers.
The FDA OK’d Bristol-Myers' Inrebic as a front-line and follow-up treatment for myelofibrosis, a rare cancer in which scarring of the bone marrow stops it from producing healthy blood cells. Roche’s Polivy and BeiGene’s Brukinsa both got lymphoma nods, with the latter becoming the first drug discovered in China to get FDA approval. Last but not least, Karyopharm’s Xpovio finally squeaked past the FDA after a roller-coaster ride, which included an advisory panel voting against its accelerated approval. It is approved for patients with multiple myeloma whose cancer worsened despite trying several other treatments.
Central nervous system disorders gained seven new drugs, including AMAG’s Vyleesi for hypoactive sexual desire disorder, SK Life Science’s seizure drug Xcopri, and a pair of migraine drugs from Eli Lilly and Allergan. Sage Therapeutics’ Zulresso became the first FDA-approved treatment for postpartum disorder, and IntraCellular Therapies' Caplyta scored a long-awaited nod for schizophrenia.
Following close behind, rare disease drugs and antibiotics nabbed four approvals apiece. Two forms of porphyrias got new drugs—Alnylam’s Givlaari and Clinuvel’s Scenesse—and transthyretin-mediated amyloidosis (ATTR) got its third drug: Pfizer’s “pipeline surprise,” Vyndaqel. It may have trailed Alnylam’s Onpattro and Ionis’ Tegsedi to market, but Vyndaqel is approved for a different variant of ATTR than the other two.
Nonprofit Global Alliance for TB Drug Development scored approval for pretomanid, to be used in combination to treat drug-resistant tuberculosis. And Nabriva brought a new type of antibiotic to the market: Xenleta, the first in a class of drugs called pleuromutilins, which target a different protein synthesis binding site than older competitors.
Steven Robins, managing partner at the New England Consulting Group, thinks the ups and downs of drug approvals from year to year depend on the maturation of new approaches. A leader discovers a new technology, or new mechanism of action, and “you have a rush from other companies that are already participating in the area to find similar technologies,” he said.
Others think the general upward trend is a result of a “friendlier” FDA.
“Swift regulatory action by the FDA moved a couple of 2020’s biggest launches into 2019," Vantage wrote. "Vertex’s latest cystic fibrosis therapy Trikafta was green lit in October—three months after filing and five months before its official PDUFA date. Global Blood Therapeutics’ sickle cell treatment, Oxbryta, won approval three months ahead of schedule.”
The speedy approvals might be a warning sign that the FDA is letting through treatments that are only slightly better than drugs that are already available.
“Concerns exist about what some consider the overuse of accelerated approvals and lack of oversight of confirmatory studies, for example, while the development of expensive new products that offer little improvement over existing therapies will continue to be held up as bad news for patients,” Vantage wrote.
And, Vantage wrote, it looks like the “increasingly cooperative and flexible regulatory regime” at the FDA is here to stay. A couple of programs up for review next year will serve as “yardsticks of the regulator’s generosity.”
These include Biogen’s Alzheimer’s prospect, aducanumab, which the Big Biotech abandoned after it failed a futility analysis but then resurrected months later.
“A green light will be interpreted as Sarepta 2.0, and a further demise in standards of evidence-based medicine,” Vantage wrote.
Robins thinks, at least in the near term, that the number of drug approvals will be “fairly consistent.”
“There will be a small number of truly innovative approaches each year and a majority of the drugs that come through—like cell therapies—we know there is going to be an acceleration of those,” he said. “The FDA has put out estimates expecting to approve 10 to 20 [cell and gene therapies] in the next year. … Whatever is beyond cell therapy, we will see a few of those and then continue to see these larger numbers of similar follow-ons with a one to three-year time lag from the first innovator."
Read on for snapshots of the drugs that earned FDA approval in 2019.