02 Analgesics and anesthetics
In 2020, two new benzodiazepines have been approved. The first was Remimazolam Tosilate (Rebenin) developed by Jiangsu Hengrui, which was listed in China for sedation during routine gastroscopy. A few months later, Remazolam besylate (Anerem) developed by PAION was launched in Japan. The relevant rights have been authorized to Mundipharma and the indication is general anesthesia.
In August 2020, Oliceridine (Olinvyk; Trevena) has been approved by the US Food and Drug Administration (FDA) for the treatment of acute pain requiring intravenous opioid analgesics without effective alternative therapy. Oliceridine is a μ-Opioid receptor agonist can achieve the analgesic effect of intravenous injection of opioid drugs, with fast onset (2-5 minutes), and patients with renal function damage do not need to adjust the dose. The drug was approved based on the results of a phase III study of the development plan, which evaluated Oliceridine in more than 1500 patients with moderate to severe acute pain. In two key efficacy studies conducted in hard tissue and soft tissue surgical models, the drug showed rapid analgesic effects with significant differences compared with placebo. Oliceridine was launched in the United States in November 2020. The drug is suitable for short-term use in hospital or other controlled clinical environment, not suitable for home use.
In September 2020, Zynrelef of Heron Therapeutics was approved by the European Commission (EC) for the treatment of postoperative pain caused by small and medium-sized surgical wounds in adults. Zynrelef is a non-opioid local analgesic with dual mechanisms of action. Zynrelef is a fixed dose compound containing bupivacaine and meloxicam; the analgesic effect lasted about 72 hours after injection. The approval of Zynrelef was based on the results of two multicenter, double-blind, positive control and placebo-controlled phase III studies (NCT03295721 and NCT03237481) conducted by Heron to evaluate Zynrelef. Both phase III studies achieved the primary endpoint and all four key secondary endpoints. Compared with normal saline placebo and bupivacaine solution (the standard local anesthetic currently used for postoperative pain control), Zynrelef can significantly relieve pain within 72 hours and reduce the use of opioids. Zynrelef significantly increased the proportion of patients who do not need opioids after surgery. Heron Therapeutics expects Zynrelef to go public in the European Union in 2021.
03 Psychopharmacology drugs
Orexin OX1/OX2 receptor antagonist Lemberexant (Dayvigo; Eisai; First marketed in the United States and soon after in Japan) is used to treat insomnia characterized by difficulty in falling asleep and/or maintaining sleep. FDA’s approval of Lemberexant was based on the results of a research project including two key phase III studies (SUNRISE 2 and SUNRISE 1). In a total of about 2,000 adult patients with insomnia, the efficacy and safety of Lemberexant compared with control drug (1 month) and Lemberexant compared with placebo (6 months) were evaluated respectively. In the study of SUNRISE 2, Lemberexant was superior to placebo in the main effective index (subjective sleep delay), and the difference was statistically significant. Lemberexant was also better than placebo in improving subjective sleep efficiency, sleep time and sleep maintenance, and the difference was statistically significant. In the SUNRISE 1 study, Lemberexant was superior to placebo in the main efficacy index (continuous sleep latency), and the difference was statistically significant. Lemberexant was also better than placebo in improving sleep efficiency and waking after falling asleep, and the results were statistically significant. Orexin (also known as hypothalamic secretin) is a kind of hypothalamic neuropeptide, which was first reported in the late 1990s. Since then, studies have found that orexin can regulate the sleep/wake cycle by maintaining arousal, and help appetite regulate and maintain energy homeostasis. There are only two kinds of insomnia drugs targeting orexin on the market. Lemberexant is the second one, and the first one is Suvorexant, which was launched in 2014.
Tasimelteon (Hetlioz), a melatonin MT1/MT2 receptor agonist developed by Vanda- pharmaceutical Inc., has been on the market for many years for the treatment of sleep arousal disorders in patients with complete blindness. Another indication of Tasimelteon was approved in the United States in 2020 for the treatment of night sleep disorders associated with Smith Magenis syndrome (SMS). SMS is a rare neurodevelopmental disease caused by a small deletion of human chromosome 17p. A key feature of SMS is that the circadian rhythm of patients is “reversed”, which makes it very difficult for SMS patients to fall asleep at night. Tasimelteon is the first SMS treatment drug approved by FDA. Capsule preparations for adults have been available and liquid preparations for children were expected to be available in the first quarter of 2021.
Lumateperonetosylate (Caplyta; IntraCellulaTherapies Inc.) an atypical antipsychotic drug based on multi system synergy, was approved by FDA in late 2019. Lumapirone has potent antagonistic activity against serotonin 5-HT2A receptor and can also bind to dopamine (D1 and D2) receptors. It is a partial agonist of presynaptic D2 receptor and an antagonist of postsynaptic dopamine receptor. In addition, preclinical data showed that as an indirect regulator of glutamatergic phosphoprotein, Lumaperone had a unique mechanism of action, which can increase the receptor D1 dependent NMDA and AMPA activities through mammalian target of rapamycin (mTOR) pathway. This mechanism of action can bring strong and rapid antidepressant effect. Lumapidone was first marketed in the United States in March 2020.
04 Respiratory system drugs
At the end of 2019, Glenmark Pharmaceuticals announced that its fixed-dose combination formulation Ryaltris (olopatadine hydrochloride/ mometasone furoate) has received marketing authorization from the Australian Medicines Agency. The compound preparation is suitable for patients with allergic rhinitis and rhinoconjunctivitis over 12 years old. The compound nasal spray can simultaneously deliver the antihistamine drug olopatadine and the corticosteroid drug mometasone furoate in a single administration. The drug was launched in Australia in 2020 by Seqirus, one of the countries with the highest allergic rhinitis index in the world (close to 20%).
Novartis’ Enerzair is a fixed-dose combination formulation that delivers the long-acting beta agonist (LABA) indacaterol acetate (long-acting muscarinic antagonists glycopyrrolate and mometasone furoate). It was approved for the treatment of asthma in Japan for the first time in June last year. A few days later, Enerzair was approved by the EMA as a maintenance treatment for the following adult asthma patients: LABA and high-dose ICS combined as a maintenance treatment cannot completely control the condition, and have had one or more acute asthma attacks in the past year. Soon thereafter, the drug completed its first global listing in Germany.
The related product Atectura (indacaterol acetate/ mometasone furoate; Novartis) was also approved for listing in the European Union and Japan last year, and was the first to be listed in Germany. Atectura is used for the maintenance treatment of adults with inhaled corticosteroids and inhaled short-acting β2 agonists that have not fully controlled the disease, and for the maintenance treatment of asthmatics in adolescents ≥12 years of age.
Trelegy Ellipta is a fixed-dose compound preparation developed by GlaxoSmithKline and approved for marketing in the United States for the treatment of asthma, a new indication. Trelegy contains the glucocorticoid receptor agonist fluticasone furoate, the muscarinic M3 receptor antagonist umaminium bromide and the β2-adrenergic receptor agonist vilanterol. The drug was first marketed in 2017 for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.
A new indication for the anti-fibrosis drug Nintedanib (Ofev; Boehringer Ingelheim) was approved by the FDA last year for the treatment of patients with chronic progressive fibrotic interstitial lung disease (ILD). This is the first FDA-approved treatment for pulmonary fibrosis that gradually deteriorates over time. Progressive chronic fibrotic ILD is a group of pulmonary fibrosis caused by different underlying diseases or conditions, including autoimmune ILD, hypersensitivity pneumonia and idiopathic non-specific interstitial pneumonia. Chronic fibrotic ILD is characterized by scarring of the lungs and rapid disease progression, and can be assessed by worsening lung function, symptoms, and/or imaging. Progressive scarring of the lungs can lead to shortness of breath and respiratory failure. The lung function of these patients gradually declines over time, which can make the patients increasingly weak and life-threatening. Nintedanib has previously been approved for the treatment of idiopathic pulmonary fibrosis and can slow down the rate of lung function decline in ILD patients with systemic sclerosis or scleroderma.