Global Approvals of Pharmaceuticals and Medical Devices in May 2019

In May 2019, orphan drugs accounted for half of the new drug approvals in Europe and the United States, replacing anti-tumor drugs as the new focus of research and development. The domestic registration and review landscape shows a favorable trend, with domestically produced devices holding a significant advantage over imported ones.

I. Global Drug Approval Status

May 2019 Drug Review Data Released: Orphan Drugs Account for Half of New Drugs Approved in Europe and the United States, Replacing Antitumor Drugs as the New R&D Hotspot.

To expedite the approval process for urgently needed new drugs already marketed overseas, the National Medical Products Administration (NMPA) selected two batches of such drugs, totaling 74 products. Denosumab injection for giant cell tumor of bone, the recombinant zoster vaccine (CHO cells), and the new hepatitis C treatment glecaprevir/pibrentasvir tablets were all approved in May. On May 5, 2019, Furamei, a Class 1 new drug independently developed by Hansoh Pharmaceutical in China, was successfully launched on the market.

(1) U.S. FDA Approval Status

Since 2019, the United States has received and approved a total of 457 applications. A total of 44 NDA/BLA drugs (excluding provisionally approved drugs) have been approved successively, which is relatively stable compared to previous years.

Figure 1. FDA-Approved Drugs, 2010–2019

In May 2019, the FDA approved a total of 74 drugs, including 7 New Drug Applications/Biologics License Applications (NDA/BLA) approvals (excluding tentative approvals). This represents a significant decrease compared to the previous month (106 total approvals, with 13 NDA/BLAs). Among these approvals were 2 new molecular entities and 2 new active ingredient drugs.

Table 1 List of NDA/BLA Approvals by the FDA in May 2019

Of the seven newly approved drugs, four are orphan drugs, accounting for 57.1%, indicating that orphan drug development has received significant attention from the FDA. Among these, several new drugs warrant particular attention, as detailed below:

(1) On May 24, PIQRAY received FDA approval. This product is an oral small-molecule PI3K inhibitor developed by Novartis, used in combination with fulvestrant for the treatment of postmenopausal women and male patients with HR+/HER2-, PIK3CA-mutated advanced or metastatic breast cancer. Approximately 40% of patients with HR+/HER2- advanced breast cancer harbor PIK3CA gene mutations. Alterations in the PI3K pathway are associated with tumor progression, treatment resistance, and disease advancement. PIQRAY is the first therapeutic agent specifically targeting PIK3CA-mutated HR+/HER2- advanced breast cancer.

(2) On May 23, SLYND received FDA approval. Developed by Exeltis, this oral contraceptive reduces the risk of pregnancy by inhibiting ovulation. As a synthetic progestin with pharmacological effects similar to those of natural progesterone, SLYND improves bleeding profiles and offers greater flexibility, maintaining contraceptive efficacy for up to 24 hours. Its clinical efficacy and safety were validated in a clinical trial involving more than 3,000 patients. The results demonstrated that SLYND’s clinical efficacy is comparable to that of combined hormonal contraceptives (CHCs), while no thromboembolic events occurred among any of the female participants, including those at high risk.

(3) On May 17, NAYZILAM received FDA approval. This product is a benzodiazepine indicated for the acute treatment of seizure clusters in patients with epilepsy aged 12 years and older. Previously, Nayzilam (midazolam) was granted orphan drug designation by the FDA. It is the first and only FDA-approved nasal spray for the treatment of seizure clusters in epilepsy, allowing non-healthcare professionals to administer timely intervention during seizures. The exact mechanism of action is not fully understood; however, it is believed to work by enhancing GABAergic neuronal transmission and facilitating the binding of GABA to its corresponding receptors. Nayzilam was acquired by UCB of Belgium for $370 million in June 2018 to expand its epilepsy research and development pipeline.

(4) On May 3, VYNDAQEL received FDA approval. This product is an oral transthyretin stabilizer developed by FoldRx Pharmaceuticals for the treatment of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) in adults. ATTR-CM is a rare and fatal heart disease, and VYNDAQEL is the first and currently only drug approved by the FDA for the treatment of ATTR-CM. In 2010, Pfizer acquired FoldRx Pharmaceuticals, thereby obtaining tafamidis. The European Medicines Agency (EMA) granted VYNDAQEL marketing authorization throughout the European Union on November 16, 2011. The FDA has designated VYNDAQEL as an orphan drug, and granted it Fast Track designation, Priority Review, and Breakthrough Therapy designation to facilitate and encourage the development of this drug for rare diseases.

(II) EMA Approval Status in the European Union

As of May 31, 2019, a total of 25 medicinal products had been approved for marketing by the European Medicines Agency (EMA), representing a significant decrease compared to previous years (36 approvals). Seven new active substances (NAS) were approved, a decline from the same period in 2018, but relatively stable compared to earlier years. See Figure 2.

Figure 2 EMA Drug Approvals by Year

In May 2019, the EMA approved a total of three medicinal products, including two containing new active substances and one generic medicine. See Table 2.

Table 2 List of Drugs Approved by the EMA in May 2019

Two orphan drugs, Waylivra and Palynziq, were among the products approved in May. Details are as follows:

(1) On May 2, Waylivra received approval from the European Medicines Agency (EMA) for the treatment of familial chylomicronemia syndrome (FCS). Waylivra is an antisense oligonucleotide (ASO) inhibitor that modulates plasma triglyceride levels by reducing the production of apolipoprotein C-III (ApoC-III). Waylivra was granted orphan drug designation by the EMA in 2014. FCS is a very rare and devastating disease caused by impaired lipoprotein lipase (LPL) function. Patients face the potential risk of acute pancreatitis and chronic complications resulting from permanent organ damage. It is estimated that approximately 3,000 to 5,000 people worldwide have FCS, with about 1,000 cases in Europe.

(2) On May 2, Palynziq received EMA approval for the treatment of patients aged 16 years and older with phenylketonuria (PKU) who are unable to adequately control their blood phenylalanine levels (blood phenylalanine exceeding 600 µmol/L). Palynziq is a polyethylene glycol-conjugated recombinant phenylalanine ammonia lyase (rAvPAL) produced in Escherichia coli, which serves as a substitute for the deficient phenylalanine hydroxylase (PAH) to reduce blood phenylalanine levels. Palynziq is a novel enzyme replacement therapy that was granted orphan drug designation by the FDA and received marketing authorization in the United States in 2018.

(3) NMPA Approval Status

In May 2019, the National Medical Products Administration (NMPA) approved a total of 52 drug marketing applications, including 41 domestically produced drugs and 11 imported drugs. Excluding different dosage forms, there were 43 unique drug varieties in total. The distribution of approved product types is shown in Figure 3.

Figure 3 Distribution of Product Types Approved in May

Table 3 List of Companies with More Than Two Approved Products in May

In May, one domestically produced Class 1 new drug and one imported Class 1 new drug were approved, along with three overseas-marketed drugs urgently needed for clinical use. Among these, four drugs were approved through the CDE Priority Review Program. See Table 4.

Table 4 List of New Drugs Approved by the NMPA in May 2019

Several drugs approved this month are worth noting, with details as follows:

(1) On May 5, pegylated loxenatide injection (brand name: Fulai Mei®) received marketing approval as a Class 1 innovative drug. This product is a long-acting GLP-1 receptor agonist developed by Jiangsu Hansoh Pharmaceutical, which promotes glucose-dependent insulin secretion and is indicated for improving glycemic control in adult patients with type 2 diabetes, requiring only once-weekly subcutaneous injection.

GLP-1 receptor agonists have been a research hotspot in glucose-lowering drugs in recent years. Hansoh Pharmaceutical’s pegylated loxenatide injection is the first domestically approved long-acting GLP-1 formulation in China. Previously approved weekly formulations, including AstraZeneca’s Byetta (exenatide) and Eli Lilly’s Trulicity (dulaglutide), were all imported products. The launch of pegylated loxenatide injection will provide new treatment options for patients with type 2 diabetes.

(2) On May 15, dacomitinib tablets (brand name: Vizimpro®) were approved by the NMPA. This product is a second-generation EGFR-targeted therapy developed by Pfizer, indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations. The approval of Vizimpro® was based on positive data from the pivotal international, multicenter Phase III clinical study ARCHER-1050, which demonstrated a significant prolongation of progression-free survival and a significant reduction in the risk of death or disease progression compared with gefitinib. This approval marks the first time in China that a drug has achieved nearly simultaneous global submission and regulatory approval in alignment with the United States, Europe, Japan, and other countries.

(3) Denosumab injection for giant cell tumor of bone and recombinant zoster vaccine (CHO cells) for herpes zoster were included in the first batch of 48 new drugs urgently needed for clinical use, due to their designation as orphan drugs and the lack of effective preventive and therapeutic measures for these diseases in China, respectively.

(4) AbbVie’s new hepatitis C treatment, glecaprevir/pibrentasvir tablets (brand name: Maviret), was included in the “Second Batch of Clinically Urgent Overseas New Drugs List” released by the Center for Drug Evaluation (CDE) on May 29, 2019, due to its “significant therapeutic advantage over existing treatments.”

Since 2018, the National Medical Products Administration (NMPA) has established a separate “fast-track” channel for new drugs already marketed abroad that are in urgent clinical need, accelerating the review and approval of new drugs for rare diseases and life-threatening conditions. To date, two batches comprising 74 drug varieties have been announced, with import registrations approved for 16 of these varieties.

II. Global Approval Status of Medical Devices

Based on the medical device review data from May 2019, the trend in domestic registration reviews in China was favorable, showing a significant advantage over imported devices. Two independently developed domestic medical devices received innovation designation and entered the special approval pathway.

(1) US FDA Approval Status

According to statistical data, in May 2019, the FDA approved a total of 252 products. Among these, 248 were marketed through the premarket notification 510(k) pathway, including 14 Class I devices, 227 Class II devices, and 7 unclassified devices; 4 medical device products were marketed through the premarket approval (PMA) pathway.

Based on the classification of devices cleared through 510(k) premarket notifications according to their specialized medical uses in the United States, it was found that orthopedic and cardiovascular products had the highest number of market approvals, as shown in Figure 5.

Figure 5 Distribution of Product Types Approved for Market via the FDA 510(k) Pathway in May 2019

(II) Approval Status in China

1. Status of Medical Devices Entering the Special Review Procedure and Priority Review Procedure

In May 2019, a total of two medical devices were granted innovative medical device status and entered the special approval process: the Diabetic Retinopathy Analysis Software developed by Shenzhen Silicon Intelligence Technology Co., Ltd., and the Endoscopic Surgical System developed by Suzhou Kangduo Robot Co., Ltd.

Meanwhile, eight medical devices were included in the priority review and approval program for medical devices, including one imported product and seven domestically produced products. The Mycobacterium tuberculosis Complex Nucleic Acid Detection Kit developed by Hangzhou Ustar Biotechnology Co., Ltd. was granted priority review status as a “medical device under the National Science and Technology Major Project.” Medtronic’s “delivery sheath” was included in the priority review program because it addresses an “urgent clinical need, and no similar product has been approved for registration in China.”

2. Status of Medical Device Products Approved for Initial Registration by the National Medical Products Administration

In May 2019, the National Medical Products Administration approved a total of 212 medical device products for initial registration. Among these, 57 were domestically produced Class III medical devices (including in vitro diagnostic reagents), and 155 were imported medical devices, comprising 103 Class I, 23 Class II, and 29 Class III products.

As of May 31, 2019, provincial-level drug regulatory authorities across China had collectively approved 321 registrations for Class II domestic medical devices and recorded 364 filings for Class I medical devices, indicating strong development potential for the domestic medical device industry.

Statistical data shows that in vitro diagnostic reagents accounted for the largest number, with a total of 227 items, representing 25% of the total. Among these, domestically produced products were the most numerous, with 168 items, accounting for 74%. The vast majority of this category consists of in vitro diagnostic analytical reagents such as test kits, quality control materials, and calibrators. Excluding in vitro diagnostic reagents, the top three categories by approved registration volume were passive surgical instruments, infusion, nursing, and protective devices, and physical therapy devices.

Table 5 Distribution of the Number of Approved and Registered Medical Device Categories in China and Imported Medical Devices in May 2019

In terms of regional distribution, manufacturers of domestically registered products are primarily concentrated in the economically developed coastal provinces. Among them, Guangdong, Zhejiang, Shanghai, and Beijing have a relatively high number of domestic medical device registrations. See Figure 6.

Figure 6 Regional Distribution of Medical Devices Approved in China