Special Report—2 years after sluggish 2016, new drug approvals hit their stride in 2018

If in 2017, the FDA was trying to make up for lost time, the agency went into overdrive in 2018, approving more than 50 new molecular entities. The strong showing in 2018 followed a more-than-respectable 46 NMEs the previous year, which came after an anemic 2016 that saw only 22 approvals. 

By the FDA’s count, it approved 59 NMEs in 2018, topping its previous record of 53 in 1996. If you’re wondering why our count is different, there are multiple reasons. We included two biologics—Andexxa and Jivi—and Inbrija, a new formulation of levodopa, in our list. We omitted other drugs, such as Akynzeo. The combination of netupitant and palonosetron first earned the FDA’s OK as an oral drug for the prevention of nausea in patients undergoing chemotherapy in 2014. The FDA approved an injectable version of Akynzeo that uses a prodrug of netupitant for the same indication in 2018 and listed it as an NME. We also omitted Omegaven, the active ingredient of which is fish oil triglycerides, and Annovera, a contraceptive ring that releases hormone medications that are already available on the market. And though the FDA listed cancer drugs Braftovi and Mektovi separately, we considered them a combination treatment, like Zepatier (elbasvir/grazoprevir) in 2016. 

With that out of the way, let’s get down to what happened in 2018. 

Predictably, cancer drugs came out tops with 16 approvals,with blood cancer treatments coming out slightly ahead of those for solid tumors. AstraZeneca’s Lumoxiti and Verastem’s Copiktra were both approved as third-line treatments for blood cancers—the former for hairy cell leukemia, a rare, slow-growing cancer, and the latter for chronic lymphocytic leukemia, follicular lymphoma and small lymphocytic lymphoma.

Several drugs were indicated for genetically defined cancers: Array BioPharma's Mektovi/Braftovi for BRAF-mutated melanoma and Agios' Tibsovo for relapsed or refractory acute myeloid leukemia with an IDH1 mutation, as well as a trio of drugs from Pfizer, namely Vizimpro for EGFR-mutated non-small cell lung cancer, Lorbrena for ALK-positive NSCLC, and Talzenna for BRCA-mutated, HER2-negative breast cancer. And who could forget Bayer and Loxo’s Vitrakvi, the "tissue-agnostic" drug that won approval to treat patients whose tumors feature a neurotrophic receptor tyrosine kinase gene fusion? 

The number of rare disease approvals almost matched that of cancer approvals. Thrombocytopenia saw two new approvals in Doptelet and Tavalisse, as did hereditary transthyretin amyloidosis (hATTR) in Alnylam’s Onpattro and Akcea/Ionis’ Tegsedi. Onpattro also had the distinction of being the first approved drug for polyneuropathy stemming from hATTR, as well as the first small interfering RNA, or siRNA, medicine. 

GW Pharma’s Epidiolex became the first cannabis-based medicine to get past the FDA. Approved for two rare forms of epilepsy, Dravet and Lennox-Gastaut syndromes, Epidiolex’s active ingredient is cannabidiol, a Schedule I drug with "no currently accepted medical use," which had to be rescheduled by the Drug Enforcement Administration (DEA) before GW could roll it out. While the DEA only rescheduled cannabidiol in the form of Epidiolex, GW Pharma’s historic approval could pave the way for other companies working on cannabis-based treatments. 

Hepatitis C, the indication that seemed to keep on giving, at least these past few years, was absent from 2018’s crop, while HIV and migraine logged three new drugs apiece. Gilead’s HIV combo drug, Biktarvy, is expected to garner as much as $10 billion in sales, arriving in time to help stave off pressure on the Big Pharma’s hepatitis C franchise. And TaiMed’s Trogarzo, approved for multidrug-resistant HIV-1, is the first HIV therapy with a new mechanism of action approved in more than a decade.

Migraine was also a hot area, with several players racing to get a first-in-class nod for their CGRP inhibitors. Amgen and Novartis won that distinction with Aimovig, which was approved in May. Teva’s Ajovy and Eli Lilly’s Emgality followed suit in September, but there are still more to come. Allergan and Biohaven are both working on oral CGRP drugs, which represent a more attractive option for patients. 

As individual drugmakers go, there was one clear winner: Pfizer, which didn’t get a drug approved until September but ended up with four approvals—all in oncology—over the course of two months. Its second approval of 2018, PARP inhibitor Talzenna, earned the FDA’s OK for BRCA-mutated, HER2-negative breast cancer, but the Big Pharma is looking to expand its repertoire to other cancers, including ovarian, pancreatic and lung. 

Most of the other companies on this year’s list got just one approval apiece, with the exception of Shire and AstraZeneca, which both got two. Bayer, Eli Lilly, Novartis, and Shionogi also got two, but their second approvals were all for partnered drugs. For the second year in a row, Bristol-Myers Squibb was the only top 15 pharma company that went without. 

So what was behind the boost in drug approvals in 2018? Evercore ISI analyst Jon Miller says it’s hard to say that there’s a trend across the board: "The most I would say is these things go in waves. That said, the agency over the past couple of years has been increasingly conciliatory. And I don’t mean that they necessarily are letting bad drugs through, but they have been maybe putting up less resistance to certain things." 

He pointed to the controversial approval of Exondys 51 in 2016 as the bellwether for this: "The FDA is becoming more willing, especially in rare diseases and restricted patient populations with high unmet need, to approve drugs on what might have counted as thin evidence five or 10 years ago." 

And while some people thought Exondys had been approved on "relatively shaky evidence," Miller said that it didn’t necessarily mean that the FDA was going to approve everything that came its way. He doesn’t think the evolution in the agency’s thinking is limited to the past two years: "I think this is a trend that has been developing for a little while and there are natural ebbs and flows in the approval cycle, as pipelines ebb and flow naturally." 

A more telling statistic would be approval rate, he said, or the number of new drug applications that are approved each year as a percentage of total applications filed. But this can be hard to track, as the FDA does not publicly release applications that are submitted but not approved, and the only real source for rejected applications is when a company announces that it has received a complete response letter, a request for more data, or the like. The FDA did not respond to a request for comment by press time. 

"According to the regulator’s own statistics applications have also risen, but not at the same rate; although not much data have been seen for 2018 yet. This uptick presumably largely reflects the FDA’s internal efforts to get new drugs to market more quickly and efficiently. Many believe that the jump in numbers is also a result of lower efficacy hurdles," wrote EP Vantage in its 2019 Preview. 

One question is what this "clement regulatory climate," to quote Vantage, might mean for the future. 

"A lot of this bull market has been driven by a super-permissive FDA. This has emboldened risk-taking by both biotech companies and investors," one investor, who asked not to be named, told Vantage.  

"[If] this surge in accelerated applications is a symptom of an industry that has been encouraged to push forward too quickly—in some cases to the detriment of both patients in terms of effectiveness and safety and investors in terms of weak commercial prospects—an era of regulatory permissiveness could hurt the sector over the longer term," Vantage wrote.

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