Recently, according to the official website of CDE, the application for the listing of the 5.1 new drug Opicapone Capsules jointly submitted by Fosun Pharma and Bial-Portela & Ca was accepted. According to the information, Opicapone Capsules is an adjuvant treatment drug for primary Parkinson's disease introduced by Fosun Pharma from Bial-Portela & Ca of Portugal. It is a new generation of catechol-O-methyltransferase inhibitors (COMT) inhibitors.

It is worth mentioning that the COMT inhibitors currently approved for listing in China include the first-generation tolcapone and the second-generation entacapone. Compared with the above similar drugs, the third-generation COMT inhibitor Opicapone has shown advantages in terms of effectiveness and safety.

Introduced by Fosun, it is expected to be listed in China

. At present, there are three COMT inhibitors listed in the world. The COMT inhibitors listed in China include tolcapone and entacapone. In addition, the combination of entacapone and compound levodopa, entacapone double dopa tablets, has been approved for listing. The Opicapone Capsules introduced by Fosun Pharma have submitted a listing application in China.
(1) Tolcapone was jointly developed by Roche, Valeant and Meda. It is the world's first COMT inhibitor approved for marketing. It was approved by EMA in August 1997 and then approved by FDA for marketing in January 1998. Its trade name is Tasmar. Tolcapone is included in the "Guidelines for the Treatment of Parkinson's Disease in China (Fourth Edition)" for the symptomatic treatment of early Parkinson's disease. It is evaluated as effective for the treatment of symptom fluctuations and may be clinically useful.

It is worth noting that tolcapone has strong hepatotoxicity and may cause severe, fatal, and acute liver cell damage in patients. It is rarely used in clinical practice.

(2) Entacapone was jointly developed by Orion Pharma and Novartis. It was approved by EMA in September 1998 and then approved by FDA for marketing in October 1999. Its trade names are Comtess and Comtan. Entacapone reduces levodopa metabolism by inhibiting the COMT enzyme, increasing the total amount of levodopa available in the brain. It is used as an adjunct therapy to the standard therapy of levodopa/benserazide or levodopa/carbidopa, for the treatment of Parkinson's disease that cannot be stabilized by standard therapy and adult patients with on-off fluctuations. In addition, the carbidopa/levodopa/entacapone combination drug Entacapone Dual Dopa Tablets developed by Orion Pharma was first approved by the FDA in 2003 for the treatment of Parkinson's disease under the trade name Stalevo.

Entacapone was approved for marketing in China in 2009 under the trade name Kedan, for the adjunctive treatment of Parkinson's disease, and was included in the national medical insurance catalog in the same year. After Entacapone was launched, its sales have increased year by year. According to Yaozhi data, the domestic sales of Entacapone tablets will reach 200 million yuan in 2023.

(3) Opicapone is a COMT inhibitor developed by Bial-Portela of Portugal. It was approved by EMA for adjunctive treatment of Parkinson's disease in June 2016. In 2020, Opicapone was approved by the US FDA for marketing as an adjunctive therapy for levodopa/carbidopa.

In 2018, Wanbang Pharmaceutical, a member company of Fosun Pharma, signed an agreement with Bial-Portela & Ca, under which Wanbang Pharmaceutical will exclusively sell Opicapone in mainland China. On November 14, 2024, the marketing application for Opicapone capsules jointly submitted by Fosun Pharma and Bial-Portela & Ca was accepted.

It has obvious advantages and may become a new round of iteration .

Parkinson's disease is a common degenerative disease of the nervous system in middle-aged and elderly people. The main clinical manifestations are motor symptoms of tremor, muscle rigidity, bradykinesia, and postural balance disorders, as well as non-motor symptoms such as sleep disorders, olfactory disorders, autonomic dysfunction, cognitive and mental disorders. Epidemiological surveys show that the prevalence of Parkinson's disease in people over 60 years old in Europe and America is 1%, and over 80 years old is more than 4%. The prevalence of people over 65 years old in China is 1.7%.

The goals of drug treatment for Parkinson's disease include achieving effective improvement of symptoms, avoiding or reducing adverse reactions, improving work ability and quality of life, adhering to "dose titration" to avoid acute adverse drug reactions, and striving to achieve the principle of "achieving satisfactory clinical effects with as small a dose as possible" to avoid or reduce the incidence of motor complications, especially dyskinesia. At present, the drugs used in clinical treatment of Parkinson's disease mainly include: compound levodopa, dopamine receptor agonists, MAO-B inhibitors, COMT inhibitors, anticholinergic drugs and amantadine.

Levodopa is the standard treatment for Parkinson's disease. After being absorbed by the human body, exogenous levodopa enters the brain and is converted into dopamine, enhancing neuronal activity and restoring the balance of brain neurotransmitters. It is the most effective symptomatic drug in the treatment of Parkinson's disease. However, a large part of levodopa is catalyzed by catechol-O-methyltransferase (CMOT) in the human body's peripheral tissues to form 3-oxy-methyldopa, which acts directly in the peripheral tissues of the brain, and most of it fails to successfully enter the brain, resulting in motor complications in most patients with disease progression and long-term use of levodopa, including symptom fluctuations and dyskinesia. Compared with the treatment time of levodopa, high doses of levodopa and long course of disease have a greater impact on the risk of dyskinesia.

Catechol-O-methyltransferase inhibitors (COMT inhibitors) mainly act on peripheral COMT, inhibit the activity of COMT enzyme, reduce the metabolism of levodopa in peripheral tissues to 3-O-methyldopa (3-OMD), enter the brain to a greater extent through the blood-brain barrier, increase the total amount of levodopa available in the patient's brain, prolong and increase the bioavailability of levodopa, thereby prolonging the duration of action of levodopa and reducing the dosage of levodopa.

Currently, COMT inhibitors can be divided into three generations of drugs. The first-generation COMT inhibitor tolcapone is rarely used clinically due to its hepatotoxicity; the second-generation COMT inhibitor entacapone has no obvious hepatotoxicity, is safer, and is more commonly used in clinical practice. It is currently a common first-line drug for Parkinson's treatment in China; the third-generation COMT inhibitor opicapone has more advantages in pharmacokinetics, efficacy, and safety than the previous generation of drugs. Opicapone has a

significant and lasting inhibitory effect on COMT. Studies have shown that the half-life of opicapone-induced S-COMT inhibition exceeds 100 hours, making it suitable for a once-daily dosing regimen; compared with entacapone, COMT activity returns to baseline levels 5 to 7 hours after medication, requiring multiple doses per day. Other studies have shown that opicapone has significant advantages over entacapone in multiple Parkinson's disease treatment effectiveness indicators such as "off" and "on" time, clinical/patient overall impression changes, and non-motor symptoms.

Catechol-O-methyltransferase inhibitors (COMT) inhibitors are currently recommended as adjuvant treatment drugs in domestic and international Parkinson's disease treatment guidelines. At present, the domestic COMT inhibitor market is dominated by the second-generation drug entacapone. The third-generation COMT inhibitor opicapol is superior to the previous generation of drugs in terms of pharmacokinetics and efficacy. If it is successfully approved for marketing, it may promote a new round of iteration of domestic COMT inhibitors.

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