Issue No. 69: FDA Approves 53 New Drugs in 2020 Despite Challenges of COVID, and 2021 Off to Record-Setting Pace
As officials of the Biden Administration consider changes to health care policy, they might want to take notice of how well drug innovation is working – and why. Of the five vaccines against COVID-19 either being widely distributed or in final Phase 3 clinical trials, three were developed by U.S. companies and one by a U.S.-German partnership. The only FDA-approved therapeutic for COVID was also developed by a U.S. firm.
Just as remarkable, despite directing tens of billions of dollars to address the challenge of the coronavirus and despite having clinical trials curtailed by the pandemic, pharmaceutical manufacturers in 2020 won approval from the U.S. Food & Drug Administration (FDA) for 53 “new molecular entities and new therapeutic biological products.” That’s the second-highest total of novel drug approvals in history.
The record, 59 new drugs, was set in 2018. Already, in the first 62 days of 2021, the FDA has approved 11 new medicines, a pace that would break the 2018 mark.
Between 2018 and 2020, the FDA has approved 160 novel medicines, or 42% more than in any such period since 1938, when President Roosevelt signed the Food, Drug and Cosmetic Act. Between 2007 and 2010, for example, just 71 novel drugs were approved.
The total of 53 drugs for 2020 does not tell the whole story of innovation last year. The figure does not include vaccines, blood products, cellular and gene therapy products, plasma derivates, and other therapies approved by the FDA’s Center for Biologics Evaluation and Research. Among those biologic approvals were a meningococcal vaccine, a treatment for bleeding disorders suffered by patients with hemophilia, and T-cell immunotherapy for a type of lymphoma that currently has a five-year survival rate of only 50%.
Generics and Biosimilars
The list also does not include emergency-use approvals, such as those for the Pfizer-BioNTech, Moderna, and Johnson & Johnson vaccines against COVID-19. Nor does the total include new indications for previously approved drugs. For example, Taltz, an Eli Lilly injectable that was originally approved by the FDA in 2016 for psoriasis, was approved in May for treating axial spondyloarthritis, a disease that causes severe, chronic back pain.
On Feb. 11, the FDA announced it had approved or tentatively approved 948 applications for generics, which are copies of branded drugs. That figure in a pandemic year is remarkable, only 6.5% shy of last year’s record. Seventy-two of the 2020 approvals were for the first generic copies of a branded drug, including treatments for HIV, multiple sclerosis and prevention of stroke. All generics, which now represent 90% of prescriptions, dramatically reduce overall drug prices by adding competition, and the FDA said in its report that “first generics are particularly important to public health.”
Unfortunately, only three biosimilars – that is, drugs that are highly similar to and has “no clinically meaningful differences” from already-approved biological products – were approved in 2020, compared with 10 in 2019 and seven in 2018. There’s a sad story that explains this paucity of biosimilars, and we will tell it in a subsequent newsletter.
Faster Approvals, Well Ahead of Other Countries
The good news, as Patrizia Cavazzoni, the acting director of the FDA’s Center for Drug Evaluation and Research, pointed out, is that 75% of the 53 novel drugs for 2020 were approved in the U.S. before any other country, giving Americans quicker access to innovative medicines.
Some 92% of the 53 drugs were approved on the first cycle – that is, the time from when the FDA accepts an application until it decides to approve. Between 2011 and 2019, the first cycle rate was 85%. In addition, 68% of approved drugs used one or more of the FDA’s programs “intended to facilitate and expedite development and review of new drugs to significantly advance treatment or address unmet medical needs for a serious or life-threatening condition,” said Cavazzoni.
A Cascade of Cancer Drugs
Of the 53 new drugs approved, 18 were for what Cavazzoni called “a wide array of cancers, particularly lung cancers,…two of which were also approved for thyroid cancer.” Lung cancer is by far the most deadly cancer in the world, with 1.8 million deaths annually, more than twice the fatalities of second-place colorectal cancer, according to the World Health Organization. (Already in 2021, four new cancer drugs have been approved.)
An example of a cancer drug approved in 2020 is Tabrectra, which treats small-cell lung carcinoma (NSCLC) that has metastasized, or spread to other parts of the body. NSCLC accounts for 85% of all lung cancers. Two other drugs for metastatic NSCLC, Gavreto and Zepzelca, were also approved last year.
The FDA started the year by approving Ayvakit, Developed by Blueprint Medicines of Cambridge, Mass., Ayvakit showed in clinical trials that it reduced gastrointestinal stromal (or connective tissue) tumors in almost 85% of patients, according to Richard Pazdur, director of the FDA’s Oncology Center of Excellence.
Also approved in 2020 were treatments for patients with urothelial cancer, which begins in the urinary tract, and for those with colorectal cancer that has metastasized or for which surgery is not an option. The FDA also approved two treatments for prostate cancer, including Orgovyx, the first hormone therapy for advanced forms of the disease. Approved as well were:
As we noted in Issue No. 59 of this newsletter, cancer in a normal (non-COVID) year is responsible for one-fifth of the deaths in the United States, but rates have been dropping quickly. Age-adjusted male rates of both lung and prostate cancer have each fallen by more than half since the early 1990s. Colon cancer rates have decreased nearly as much. For women, breast cancer rates are down by about one-third.
Behind the Rise in 5-Year Cancer Survival Rates
There are several reasons for the declines, including the reduction in tobacco use, earlier detection through better imaging techniques, and improved surgical procedures. But a study by Seth Seabury and colleagues, published in the Forum for Health Economics and Policy in 2016, estimated that 73% of the success in fighting cancer is attributable to drugs.
Since 1975, the proportion of people diagnosed with specific cancers who have survived at least five years has risen by 54% for lung cancer, 36% for colon, 50% for prostate, and 21% for breast. Five-year survival rates for breast cancer vary widely, based on the stage at which detection occurs. The rate is 99% for a cancer that has not spread, 85% for one that has spread minimally beyond its original site, and 27% for distant-stage disease, according to a 2017 American Cancer Society report. Overall for breast cancer, the five-year survival rate is 90%; for prostate cancer, 98%; for melanoma, 92%.
Progress against all cancers will depend heavily on new medicines, whose main source will undoubtedly be the United States. According to PhRMA, the trade association, “1,300 medicines and vaccines for cancer…are in clinical trials or awaiting review by the U.S. Food and Drug Administration.”
As a Wall Street Journal editorial headline in January said, the U.S. is “where you want to get cancer.” The piece cited a 2019 study in The Lancet that found that someone diagnosed with pancreatic cancer between 2010 and 2014 had nearly twice the likelihood of surviving five years in the U.S. than in the U.K. The five-year survival rate for brain cancer was 36.5% in the U.S., 27.2% in France, and 26.3% in the U.K. For stomach cancer: 33.1% in the U.S., 26.7% in France, and 20.7% in the U.K. A major reason is that drugs that are developed in the U.S. become available more quickly to American patients.
Between the start of 2017 and March 3 of this year, the FDA had approved 58 new cancer drugs, many of them using new immunotherapy techniques. The journal Nature notes that, on average over the past five years, 25% of new drug approvals were for cancer. Last year, the proportion was 34%.
Drugs for COVID, Hormone Deficiency, Migraine, Nausea, Malaria, Parkinson’s, and Much More
Cancer was not the only disease targeted by the 53 novel drugs of 2020. Perhaps the most widely recognized was remdesivir, the first FDA-approved medication in the U.S. for the treatment of hospitalized adults and adolescents with COVID-19. Now called Veklury by its Silicon Valley developer, Gilead Sciences, it was given Emergency Use Authorization in May and final approval in October, just nine months after the pandemic began. Gilead was expected to produce 2 million courses of the drug, which is administered intravenously, by the end of 2020.
There were other approvals for drugs to fight infectious disease as well: Rokubia, developed by Viiv Healthcare of North Carolina, for patients with HIV that can’t be treated successfully by other medications because of resistance or intolerance, plus drugs for chronic hepatitis C and for hospital- and ventilator-acquired bacterial pneumonia.
The sheer variety of new therapies approved in 2020 is impressive. Some examples:
Other drugs approved in 2020 treat severe obesity, head lice, Duchene muscular dystrophy, acne, severe malaria, overactive bladder, rare conditions related to premature aging, Parkinson’s Disease, multiple sclerosis, high cholesterol, chronic constipation, and more.
It’s significant that many of the medications were developed by smaller companies, which count on capital investment over many years with no guarantee that a drug will complete successful clinical trials and be approved for use. The average cost of bringing a single drug to market is about $3 billion, as this Scientific American article explains.
Drugs Account for More Than One-Fourth of R&D
The National Center for Science and Engineering Statistics, a division of the National Science Foundation, reported in January that “businesses performed $114.5 billion of research and development [R&D] with health or medical applications in the United States in 2018,” the latest data. That is fully 26% of the total $441 billion spent in R&D by businesses that year. According to the Center, pharmaceutical manufacturing accounted for 62% of health-related R&D, or $75 billion. Biotechnology R&D for pharmaceutical manufacturers has soared, the Center reported, from $17 billion in $46 billion in 2018.
This is a system that seems to work. Developers have an incentive to plough billions into discovering new pharmaceuticals. As Dhruv Khullar and colleagues wrote in the New England Journal of Medicine last year:
During the innovation period, a drug is developed and tested but cannot be sold. Only a small minority of drug products are ultimately approved by the FDA, and for those that are, this approval constitutes the start of the monopoly period, during which no other corporation can manufacture and sell the drug. After the various patents and exclusivity periods of a drug expire, the competitive period commences. Other corporations can now produce and market identical copies (i.e., generic or biosimilar drugs) of the innovator product (i.e., the brand-name drug).
Those competitors drive down prices, creating what many consider a virtuous cycle of innovation. The result: vaccines and therapeutics against COVID-19 produced in record time and 52 other new medicines approved by the FDA in the trying circumstances of 2020.
Threats to a Virtuous Cycle
The system, however, has its opponents. Four months before leaving office, Donald Trump ordered certain Medicare drug prices to be linked to prices in European countries with price controls – in effect, importing those controls to the United States and artificially putting a lid on prices. The result, inevitably, will be less innovation. In a study of an original, milder attempt at international indexing in legislation that passed the House, the consulting firm Vital Transformation concluded that such reference pricing “penalizes innovation, targets companies with the most advanced, newest products in the market for what are often the most challenging diseases.”
Reference pricing, the study found, “will radically reduce the amount of liquidity available for investments into new products/mergers/partnerships etc., negatively impacting market entry of new medicines.” The analysis examined 64 drugs that came to market over the past 10 years under biotech partnerships that have been so productive lately. With an international pricing index in effect, there would have been “56 fewer approvals of medicines originating from these small biotech companies, a reduction of nearly 90 percent.” The largest overall impact would be seen in the treatment of cancers.
An earlier study by Thomas Abbott and John Vernon, published as a working paper by the National Bureau of Economic Research, found that “cutting prices by 40 to 50 percent in the United States will lead to between 30 and 60 percent fewer R and D projects being undertaken in the early stage of developing a new drug.”
The executive order issued by former President Trump was blocked by a federal judge in late December, just before it was set to take effect on the grounds that it had been rushed through without giving the public a chance to comment. Litigation remains active in several states. So far, the Biden Administration has not taken a position on what Trump called a “most-favored nation” pricing index. If the new President looks at health care reform in a comprehensive way, he will almost certainly recognize that….
At any rate, it’s hard to dispute that, in the difficult year of 2020, dozens of newly approved medicines are something to celebrate.
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