50+ anti-PD drugs have been approved for marketing; multi-enterprise joint deployment, Nuggets innovative therapies, AbbVie, Biogen...

Parkinson's disease (PD) is the second most common chronic progressive neurodegenerative disease after Alzheimer's disease.
It is characterized by progressive loss of dopaminergic neurons in the brain and the formation of Lewy bodies, mainly manifested as bradykinesia.
Movement disorders such as myotonia, muscle rigidity, tremor, abnormal posture and gait, often accompanied by a variety of non-motor symptoms such as hyposmia and sleep disturbance, bring huge physical and mental burdens to patients and their families
.
According to statistics, PD affects about 10 million people in the world, and with the intensification of global aging, the number of PD patients will further increase
.
"On-off phenomenon" (ON-OFF) is a complication in the later stage of PD drug treatment.
"On" means that the drug treatment has a significant therapeutic effect on the patient, and the patient can exercise; "OFF" means that the patient is receiving treatment.
Loss of motor ability after a period of time due to low levels of dopamine between oral intakes
.
At present, there is no cure for PD, and its treatment methods and means include drug therapy, surgical treatment, exercise therapy, psychological counseling and nursing care, among which drug therapy is the first choice and the main means in the entire treatment process
.
According to incomplete statistics from Yaozhi.
com, more than 50 PD drugs have been approved for marketing in the world
.
According to different mechanisms of action, the marketed PD drugs can be roughly divided into anticholinergic drugs, dopamine-promoting drugs, dopamine replacement drugs, dopamine receptor agonists, B-type monoamine oxidase inhibitors, catechol-O-methyl There are six classes of transferase (COMT) inhibitors
.
Among them, anticholinergic drugs are mainly used for PD patients with tremor
.
COMT inhibitors are mainly used as adjuvant therapy for levodopa to increase the efficacy of levodopa and reduce the dosage of levodopa.
They are suitable for severe PD patients with obvious fluctuating symptoms.
They are clearly recommended by current European, American and domestic treatment guidelines.
First-line drugs for adjuvant dopamine therapy in PD patients
.
MAO-B inhibitors are the first-line treatment drugs for PD and are mainly used in patients with early PD.
Studies have confirmed that they protect neurons by resisting oxidative stress, inhibiting synuclein aggregation, reducing apoptosis and neurotrophic effects.
Some clinical trials It has been shown that it may delay PD progression
.
Moreover, in recent years, global regulators have also approved several PD drugs (see the table below for details), including the third-generation COMT inhibitor Ongentys, the MAO-B inhibitor Xadago, and other new models of traditional PD drugs
.
In addition, Insightec's ExablateNeuro device was approved by the FDA in 2018 for the treatment of tremor-predominant PD, and in November 2021 for the treatment of advanced PD patients with symptoms of mobility, stiffness or dyskinesia
.
Also, it is worth mentioning that ExablateNeuro uses focused ultrasound to precisely locate and ablate the globus pallidus in a pallidotomy, without the need for an incision, without the need for brain implantation, and with less risk of infection than invasive procedures
.
Ongentys is a novel, oral, selective, long-acting, peripheral COMT inhibitor that protects levodopa by reducing the breakdown of levodopa in the blood, allowing more levodopa to reach the brain and prolonging its clinical effect , to help patients achieve motor symptom control
.
In June 2016, the drug was approved by the European Union as adjunctive therapy to a levodopa/dopa decarboxylase inhibitor for adult patients with PD who are unable to stabilize end-motor fluctuations on these combination therapies
.
In April 2020, Ongentys 25mg and 50mg capsules were approved by the FDA as an adjunctive therapy to levodopa/carbidopa in PD patients who are experiencing motor fluctuations, becoming the first once-daily FDA-approved COMT inhibitors
.
istradefylline is an orally administered selective adenosine A2A receptor antagonist (adenosine is a neuromodulator that is widely distributed in the human body, adenosine A2A receptors in the brain are found in the basal ganglia, basal ganglia Playing an important role in motor control, the basal ganglia were found to be degenerated or abnormal in PD patients)
.
In May 2013, istradefylline was marketed in Japan for PD patients treated with levodopa-containing preparations to improve the phenomenon of "loss of efficacy" under the brand name Nouriast
.
In August 2019, the drug was approved in the U.
S.
as an add-on therapy to levodopa/carbidopa in adult patients with PD who are experiencing an "OFF" event under the brand name Nourianz
.
Inbrija is using Acorda's ARCUS platform to develop a dry powder formulation of levodopa designed to deliver precise doses to the lungs, and was approved by the FDA in December 2018 for PD off-period (OFF) intervals receiving carbidopa/levodopa therapy sex therapy
.
It is worth mentioning that Inbrija is the first inhaled levodopa to receive regulatory approval, the drug is easy for patients to operate by themselves and is suitable for on-demand treatment during the OFF period
.
Kynmobi sublingual film is a new dosage form of apomorphine (apomorphine is a dopamine D2 receptor agonist used as a rescue medication for OFF events), approved by the FDA in May 2020 for motor symptoms in patients with PD Fluctuating acute intermittent therapy
.
Notably, Kynmobi is the first and only sublingual therapy for fast, on-demand treatment of Parkinson's disease OFF events, and can be used up to 5 times a day
.
Northera is a synthetic catecholamine that is directly converted to norepinephrine by decarboxylation, resulting in elevated norepinephrine levels in the central and peripheral nervous systems
.
In addition, it is worth mentioning that the CDE official website recently showed that the import application of ZambonS.
pA/Jingding Pharmaceutical's "Safinamide Tablets" was accepted
.
Safinamide is a highly selective and reversible third-generation monoamine oxidase (MAO-B) inhibitor with dual dopaminergic and non-dopaminergic mechanisms.
The original drug Xadago was approved by the FDA in March 2017 as an additional Treatment medication for people with Parkinson's disease who are taking levodopa/carbidopa and have "off" episodes
.
It becomes the first new chemical entity approved in the United States for the treatment of Parkinson's disease in more than a decade
.
Today, China's listing application or acceptance has brought new options for innovative therapies and drugs to domestic patients
.
In addition, there are currently a number of new PD treatments under development around the world, as shown in the table below
.
ABBV-951 is a continuous subcutaneous infusion solution of levodopa prodrug and carbidopa prodrug developed for the treatment of patients with advanced PD whose motor symptoms are not controlled by oral medications
.
Published results of the M15-736 head-to-head superiority phase 3 study of this drug versus oral levodopa/carbidopa show that ABBV-951 is statistically superior to oral LD/CD in reducing motor fluctuations in patients with advanced PD , reaching the primary endpoint
.
mesdopetam is a novel dopamine D3 receptor antagonist developed for the prevention and treatment of levodopa-induced dyskinesia (LID) in PD patients, as well as the treatment of Parkinson's disease psychosis (PDP)
.
Data from completed Phase 1b and 2a clinical programs show that in PD patients undergoing LID, mesdopetam treatment resulted in substantial improvements in clinically relevant endpoints, reduced the time PD patients experienced dyskinesia, and prolonged patients' "ON".
" period
.
In July 2021, Ipsen entered into a licensing agreement with IRLAB to acquire exclusive global development and commercialization rights for mesdopetam
.
NE3107 is an oral, blood-brain barrier-crossing small molecule compound with anti-inflammatory, insulin-sensitizing and ERK-binding properties that selectively inhibits inflammation stimulated by ERK and NFκB
.
Preclinical studies show that NE3107 is as effective as levodopa in improving PD motor symptoms
.
Furthermore, the drug has greater prokinetic activity when combined with levodopa than NE3107 or levodopa alone
.
In addition, NE3107 in combination with levodopa reduced the severity of levodopa-induced dyskinesia (LID), but not the beneficial effects of the drug on motor symptoms
.
In January this year, the Phase 2 clinical study NM201 (NCT05083260), which evaluated the potential promotor effects of NE3107 in PD patients, completed the first patient dosing
.
CVN424 is an innovative therapy based on Cerevance's drug discovery platform that selectively targets the dopamine D2 receptor-dependent indirect signaling pathway associated with Parkinson's disease, and is designed to produce the same positive effects as levodopa or deep brain stimulation while at the same time , to avoid adverse reactions
.
Published Phase 2 clinical study results showed that after 4 weeks of treatment, high-dose CVN424 improved the "OFF" period by 1.
3 hours and increased the "ON" time without dyskinesia compared with placebo
.
In addition, unlike other adjuvant therapies co-administered with levodopa, CVN424 decreased daytime sleepiness indicators in patients compared with placebo
.
DA01 is a clinical trial-stage biopharmaceutical company BlueRock, a wholly-owned subsidiary of Bayer Group, which uses pluripotent stem cells to generate dopaminergic neurons.
In July 2021, it was granted Fast Track designation by the FDA for the treatment of PD, and the drug was evaluated in January this year for the treatment of advanced stage First patient dosing in an open-label Phase 1 study in PD patients
.
NBIb-1817 is a gene therapy using an AAV2 viral vector carrying a transgene expressing human aromatic L-amino acid decarboxylase (AADC), designed to help convert levodopa to dopamine by expressing the AADC enzyme in brain cells, Thereby improving the patient's motor symptoms
.
In June 2018, the drug was granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA for the treatment of PD patients with difficult medical management and motor fluctuations
.
Published results of a Phase 1b clinical trial of the drug in PD showed that of 15 patients with advanced PD who received a single gene therapy treatment, 14 patients still experienced improvement in disease grade after 3 years of treatment
.
The drug can not only continue to improve the patient's motor function, but also reduce the patient's need for oral medication
.
DNL201 is a small molecule leucine-rich repeat kinase 2 (LRRK2) inhibitor that modulates lysosomal function (LRRK2 gene mutation is one of the most common genetic causes of PD)
.
In December 2018, Denali Therapeutics initiated a Phase 1b clinical trial of DNL201 in PD patients
.
PBT434 is a new generation of quinazoline small molecule drugs designed to block the aggregation and accumulation of α-synuclein
.
The findings, published in the neuropathology journal ActaNeuropathologica Communications, show that PBT434 shows the potential to prevent iron-mediated neurodegenerative disease and alpha-synuclein toxicity in multiple animal models of Parkinson's disease
.
According to the latest market research report by MarketsandMarkets, the global PD therapeutics market size is expected to grow from USD 4.
24 billion in 2017 to USD 5.
69 billion in 2022, with a compound annual growth rate of 6.
1%
.
In recent years, more and more pharmaceutical companies have exploited the potential of the PD market, actively deployed the PD drug market, and jointly developed or introduced new PD treatments with other companies
.
In November 2017, UCL and Synpromics reached a collaboration to generate a series of synthetic gene promoters for the central nervous system (CNS) to develop gene therapy for the treatment of PD
.
In August 2018, AxovantSciences obtained the exclusive global license from OxfordBioMedica to develop and promote the PD gene therapy AXO-Lenti-PD (formerly OXB-102)
.
In February 2019, AbbVie and Voyager Therapeutics said they would launch a $1.
5 billion gene therapy program that will focus on treating PD and other diseases also caused by abnormal accumulation of alpha-synuclein
.
In August 2020, Biogen and Denali Therapeutics reached an agreement to jointly develop and promote Denali's LRRK2 small molecule inhibitor DNL151 for the treatment of PD
.
In June 2021, Caraway Therapeutics entered into an exclusive collaboration and option agreement with AbbVie to develop and commercialize Caraway's small molecule therapy targeting TMEM175
.
TMEM175 is a potassium channel essential for lysosomal function associated with PD and other neurodegenerative diseases
.
In July 2021, Ipsen entered into an exclusive license agreement with IRLAB to acquire exclusive worldwide development and commercialization rights to the D3 receptor antagonist mesdopetam for the treatment of dyskinesia (LID) in patients with PD following levodopa therapy
.
In December 2021, UCB announced that it had entered into a global collaboration agreement with Novartis to jointly develop and commercialize UCB's investigational PD therapies, including the potential "first-in-class" oral small molecule alpha- Synuclein misfolding inhibitor UCB0599 (currently in Phase 2 clinical development)
.
In March 2022, Yisi Bio signed an exclusive license agreement with BRITANNIA, a British company under the STADA Group, to obtain the rights to develop and commercialize the latter's subcutaneous injection of apomorphine for the treatment of PD in mainland China, Hong Kong, and Macau.

.