FDA’s 2019 Drug Approvals: 42 Novel Drugs, 9 Biosimilars, and 3 Pending Decisions Highlight a Year of High-Impact Therapies

As of November 29, 2019, the FDA has approved a total of 42 new drugs and 9 biosimilars this year. Additionally, three new drugs have PDUFA dates in December, bringing the projected total number of new drug approvals by the FDA in 2019 to 45. Compared with 2017 and 2018, 2019 will see the lowest number of new drug approvals by the FDA; however, the quality remains high, as exemplified by Skyrizi, Zolgensma, Rozlytrek, and Brukinsa. This article summarizes the 42 new drugs and 9 biosimilars approved by the FDA in 2019, along with the three new drugs awaiting FDA decisions in December.

► FDA Approves 42 New Drugs, Marking a Three-Year Low

As of November 29, the FDA had approved a total of 42 new drugs in 2019, compared with 57 and 62 new drug approvals in 2017 and 2018, respectively. Thus, 2019 can be described as a “sluggish” year for FDA new drug approvals. The U.S. government experienced several shutdowns from late 2018 to early 2019; additionally, the resignation of former FDA Commissioner Scott Gottlieb sent shockwaves through the biopharmaceutical industry. These factors may have impacted the approval of new drugs.

Table 1. Forty-two New Drugs Approved by the FDA as of November 29, 2019

Although the quantity is slightly insufficient, the quality is by no means lacking. Examples include highly valuable new therapies such as Skyrizi for psoriasis, the gene therapy Zolgensma, the broad-spectrum anticancer drug Rozlytrek, and Brukinsa, BeOne Medicines’ first FDA-approved new drug, along with multiple other first-in-class products across various disease areas.

• Highly Valuable New Psoriasis Drug Skyrizi

On April 23, 2019, the FDA approved Skyrizi (risankizumab-rzaa), an interleukin-23 (IL-23) inhibitor, for the treatment of adults with moderate-to-severe plaque psoriasis. Psoriasis, also known as "niupixuan" in Chinese, is a common autoimmune disease. Analysts projected that Skyrizi’s annual sales would reach $3.196 billion in 2024, making it the most valuable new drug approved by the FDA in 2019.

Upon approval, Skyrizi will enter a highly crowded market, with competitors including Taltz, Siliq, Tremfya, and Ilumya. Among these, Tremfya and Ilumya are selective IL-23-targeting biologic therapies similar to Skyrizi.

Skyrizi demonstrates the best efficacy among this class of drugs, which will facilitate its market launch and promotion. Its Phase III clinical trial results are outstanding, with approximately 75% of patients treated with Skyrizi achieving a 90% improvement in the Psoriasis Area and Severity Index (PASI).

Furthermore, the advantages of Skyrizi lie not only in its efficacy but also in its convenience of use. After the initial dose of Skyrizi, the second dose is administered four weeks later, and thereafter, patients require only four injections per year. In contrast, Tremfya requires injection every eight weeks. Additionally, patients can self-administer Skyrizi after receiving proper training.

• Gene Therapy Zolgensma – The Most Expensive Drug in History

On May 24, 2019, the FDA approved the gene therapy Zolgensma for marketing, for the treatment of pediatric patients under 2 years of age with spinal muscular atrophy (SMA) caused by SMN1 allelic mutations, at a one-time cost of $2.125 million.

Zolgensma is a one-time gene replacement therapy that delivers a functional SMN1 gene into patients via adeno-associated virus serotype 9 (AAV9), replacing the defective SMN1 gene and thereby enabling the effective production of fully functional SMN protein. Compared with Spinraza, another SMA gene therapy previously approved by the FDA, Zolgensma (AVXS-101) offers advantages in both efficacy and cost-effectiveness.

Therapeutic Approaches of Spinraza and Zolgensma

• Rozlytrek, the third broad-spectrum anticancer drug

On August 15, 2019, the FDA announced the accelerated approval of Rozlytrek (entrectinib), developed by Roche, for the treatment of adult and adolescent cancer patients with NTRK gene fusions who have no other effective treatment options.

Rozlytrek is a selective tyrosine kinase inhibitor designed to target NTRK and ROS1 gene fusions, capable of inhibiting the kinase activity of TRK A/B/C and ROS1. Rozlytrek was first approved for marketing in Japan this June for the treatment of patients with advanced, recurrent solid tumors harboring NTRK gene fusions.

Rozlytrek Molecular Formula (Image source: Wikipedia)

Rozlytrek is the third tumor-agnostic, broad-spectrum anticancer therapy approved by the FDA, following Keytruda and Vitrakvi. It targets specific genetic drivers of cancer rather than the tissue type of tumor origin.

• BeOne Medicines' First FDA-Approved New Drug, Brukinsa

On November 14, 2019, BeOne Medicines (BeiGene) announced that Brukinsa (zanubrutinib) received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with mantle cell lymphoma (MCL) who had previously received at least one prior therapy. As the first domestically developed and independently innovated anti-cancer drug from China to be approved for marketing in the United States, it rewrote the awkward history of Chinese anti-cancer drugs being “only imported, not exported.”

Brukinsa is a small-molecule Bruton’s tyrosine kinase (BTK) inhibitor independently developed by BeOne Medicines. It is currently undergoing extensive global pivotal clinical trials as a monotherapy and in combination with other therapies for the treatment of various B-cell malignancies.

The two New Drug Applications (NDAs) for Brukinsa for the treatment of patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) and patients with R/R chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have been included in the priority review by the NMPA.

• First-in-class products across multiple therapeutic areas:

1) Egaten (Novartis): On February 13, 2019, the FDA approved Egaten, the first therapy for the treatment of fascioliasis, for use in patients aged 6 years and older.

2) Zulresso (Sage Therapeutics): On March 19, 2019, the FDA approved the launch of Zulresso, the first new drug for the treatment of postpartum depression (PPD).

3) Vyndaqel (Pfizer): On May 3, 2019, the FDA approved the first new drug, Vyndaqel, for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM).

4) Turalio (Daiichi Sankyo): On August 2, 2019, the FDA approved Turalio, the first and only drug authorized for the treatment of tenosynovial giant cell tumor (TGCT).

5) Xenleta (Nabriva Therapeutics): On August 19, 2019, the FDA approved Xenleta, the first intravenous and oral antibiotic with a novel mechanism of action in nearly two decades, for the treatment of community-acquired bacterial pneumonia (CABP).

6) Reblozyl (Celgene & Acceleron): On November 8, 2019, the FDA approved Reblozyl, the first new drug for the treatment of beta-thalassemia. Beta-thalassemia is primarily prevalent in countries along the Mediterranean coast and in Southeast Asia, with a high incidence in southern China.

7) Givlaari (Alnylam): On November 20, 2019, the FDA approved the launch of Givlaari, the first new drug for the treatment of acute hepatic porphyria (AHP) in adults. Givlaari has sequentially received orphan drug designation from both the EMA and the FDA, eligibility for the EMA’s accelerated assessment procedure, and FDA Breakthrough Therapy designation.

• Major advances across multiple fields:

1) Mayzent (Novartis, 2019-03-26): The first and only therapy specifically approved by the FDA for active secondary progressive multiple sclerosis (SPMS) in the past 15 years.

2) Pretomanid (TB Alliance, 2019-08-14): The third new anti-tuberculosis drug approved by the FDA in nearly 40 years, and the first new tuberculosis drug developed and marketed by a non-profit organization.

3) Inrebic (Celgene, 2019-08-16): The first new drug for myelofibrosis in nearly a decade.

4) Aklief (Galderma, 2019-10-04): The first retinoid molecule approved by the U.S. FDA for the treatment of acne in over two decades.

5) Reyvow (Eli Lilly, 2019-10-11): The first new class of acute migraine treatment drug approved by the FDA in more than two decades.

• Three new diagnostic drugs:

1) Ga-68-DOTATOC (Advanced Accelerator Applications, 2019-08-21): It consists of the positron-emitting radionuclide gallium-68 conjugated to the somatostatin (SST) analog DOTATOC, and can be used for the diagnosis of neuroendocrine tumors (NETs).

2) Fluorodopa F 18 (The Feinstein Institutes for Medical Research, 2019-10-10): A radioactive diagnostic agent used in positron emission tomography (PET) to visualize dopaminergic nerve terminals in the brain striatum for the evaluation of adult patients with suspected Parkinson’s disease.

3) ExEm Foam (Giskit B.V., 2019-11-07): Used to assess tubal function in women with confirmed or suspected infertility.

► 9 biosimilars, an increase of 2 from last year

As of November 29, 2019, the FDA had approved a total of 25 biosimilars. In 2019 alone, nine biosimilars were approved, two more than in 2018, demonstrating the FDA’s ongoing efforts to promote competition in biologics and facilitate the market entry of biosimilars. Biosimilars are highly similar to FDA-approved biological products (reference biologics) and exhibit no clinically meaningful differences.

The reference products for biosimilars approved by the FDA in 2019 were primarily held by Roche, AbbVie, and Amgen. Roche: Herceptin (Ontruzant, Trazimera, Kanjinti), Avastin (Zirabev), Rituxan (Ruxience); AbbVie: Humira (Hadlima, Abrilada); Amgen: Enbrel (Eticovo), Neulasta (Ziextenzo).

Among the 25 biosimilars approved by the FDA, there are five Humira biosimilars, five Herceptin biosimilars, two Enbrel biosimilars, two Avastin biosimilars, three Remicade biosimilars, and three Neulasta biosimilars. Due to differing approaches by the FDA and the EMA toward biosimilars and patent protection for originator products, the development of biosimilars has progressed rapidly in the European Union but slowly in the United States; not all FDA-approved biosimilars are commercially available.

Table 2: FDA-Approved 25 Biosimilars as of November 29, 2019

► Three New Drugs with PDUFA Dates in December Awaiting FDA Decisions

With 2019 not yet concluded and December still remaining, three candidate drugs—ubrogepant, Vascepa, and lumateperone—are awaiting FDA decisions. If these three products are successfully approved for market launch, the total number of new drug approvals by the FDA in 2019 could reach 45.

Table 3 Three Candidate Drugs Under PDUFA in December 2019

Ubrogepant is a novel, highly potent, oral calcitonin gene-related peptide (CGRP) receptor antagonist developed by Allergan, currently under development for the treatment of acute migraine. To date, three monoclonal antibody-based migraine medications targeting the CGRP receptor have been marketed: Aimovig (erenumab-aooe, Amgen), Ajovy (fremanezumab-vfrm, Teva), and Emgality (galcanezumab-gnlm, Eli Lilly). In contrast to these three agents, which are used for prophylaxis, ubrogepant is administered after symptom onset. Furthermore, ubrogepant is taken orally, whereas the other three are administered via subcutaneous injection, offering greater convenience in administration.

Vascepa (icosapent ethyl) capsules are a high-purity, single-molecule prescription product containing eicosapentaenoic acid (EPA), extracted from deep-sea fish through a rigorous and complex FDA-regulated manufacturing process. In 2012, the FDA approved Vascepa as an adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridemia (≥500 mg/dL).

Based on the results of the 2018 REDUCE-IT™ trial, Amarin submitted a supplemental New Drug Application (sNDA) to the FDA in March 2019 for the reduction of cardiovascular risk. On May 29, 2019, the FDA formally accepted the sNDA for Vascepa for the indication of reducing cardiovascular risk and concurrently granted it Priority Review designation.

Lumateperone is a first-in-class small-molecule drug developed by Intra-Cellular Therapies (ICT) that selectively and simultaneously modulates three neurotransmitter pathways—serotonin, dopamine, and glutamate—implicated in severe diseases. Lumateperone may demonstrate efficacy across a range of psychiatric symptoms, with improved psychosocial functioning and favorable tolerability, potentially benefiting patients with a spectrum of neuropsychiatric and neurodegenerative disorders.

Currently, the New Drug Application (NDA) for lumateperone in the treatment of schizophrenia is under review by the FDA. Intra-Cellular Therapies (ICT) is also developing lumateperone for other psychiatric disorders, including behavioral disturbances in patients with dementia, Alzheimer’s disease, depression, and other neuropsychiatric and neurological conditions.

Reference Source:

1. FDA Official Website

2. Before 2019 closes, the FDA has 3 key approval decisions to make