Luye Pharma Group Ltd. won marketing approval in China for its risperidone microspheres for injection to treat schizophrenia, which the company said is the first formulation developed by a Chinese company in the space to get a green light.

Under the trade name Ruixintuo, the long-acting drug is administered once every two weeks by intramuscular injection. That gives patients the choice to not take daily oral antipsychotic drugs. Ruixintuo can also improve medication compliance as patients are less likely to skip a dose or suffer an immediate relapse in the event of a delay.

The marketing of Ruixintuo is set to challenge Risperdal Consta (risperidone) developed by Johnson & Johnson and Alkermes plc, which has been marketed in China since 2009.

Unlike Risperdal Consta, Ruixintuo does not require oral supplementation after the first injection.

Luye said accelerating the release of the drug is key to the effectiveness of the product. The release of Risperdal Consta starts from day 21 onward on average and would require oral supplementation during the initial three weeks, but if the release starts earlier, the overlap increases the risks for patients, Luye Global R&D President Youxin Li told BioWorld.

“We believe the 21-day administration of oral formulation is absolutely unnecessary and brings risks to patients, so we aimed to remove this step in the drug design phase,” Li said.

By comparison, the release of Ruixintuo starts within three days, eliminating the need for oral supplementation and lowering risks for patients. Ruixintuo also leads to faster steady plasma drug levels than Risperdal Consta, resulting in fast symptom control for acute patients.

“Our technique and excipients are different from those of Risperdal Consta,” he explained. “The different excipients enable faster release of our drug, and our technique improves the mechanism of drug release to accelerate it.”

Another highlight is rapid adjustment of drug dosage. After a patient stops taking Ruixintuo, the concentration of the drug in the human body drops faster than that of Risperdal Consta. That makes it easier for doctors to adjust dosage according to the patient’s condition.

“It is the first time in the clinic that it is possible to adjust drug dosage of a long-acting formulation used at the acute phase, an issue remained unsolved for a long time,” Li said.

“Long-acting formulations are not used often because it is not convenient to adjust drug dosage. When we designed our product, we wanted to make rapid adjustment possible for patients at the acute phase.”

$300 million global revenue

Li noted that there are about 30 million patients with schizophrenia in China, but only a little more than 1% of those patients use a long-acting drug. The number is 20% in the U.S., 15% in Europe and almost 10% in Japan, which points to the great market potential of Ruixintuo in China.

The U.S. is expected to be the second market for Ruixintuo following China.

Luye submitted an NDA with the FDA in March 2019, claiming it to be the first formulation developed in China in the space to enter this regulatory stage.

The drug has also completed a phase I trial in Europe and has received patents in mainland China, Hong Kong, the U.S., Europe, Japan, South Korea, Russia, Canada and Australia that will expire in 2032.

“Considering the markets in China and abroad, we estimate Ruixintuo to generate global revenue of $300 million,” Li said.

More work in CNS

Ruixintuo was developed based on Luye’s long-acting and extended-release technology platform. Li said Luye adopted a universal technique for microsphere production, which does not require different equipment to develop every single product.

With this technology platform, Luye has developed as many as eight products, and the company plans to file NDAs for one or two every year over the next three years.

Developing long-acting formulations is one of the key approaches that Luye has adopted to tackle CNS diseases.

“For schizophrenia, we are developing long-acting formulations that are administered once a month, or every three months or six months,” Li told BioWorld. “And for Parkinson's disease, we are developing products that are administered once a week, once a month or every two months.

“But we also work on innovative drugs, which goes in parallel with our long-acting formulations. We have an extensive pipeline in treating schizophrenia and Parkinson's disease. In the next three to five years, our products will start emerging one by one,” he said, adding that Luye will further consolidate its presence in the CNS space.

Luye is known as a CNS specialist. In May 2018, the company made a high-profile $546 million deal with Astrazeneca plc to acquire the rights of Seroquel (quetiapine fumarate) and Seroquel XR. Seroquel is indicated for schizophrenia and bipolar disorder, while Seroquel XR is used to treat major depressive disorder and generalized anxiety disorder.

As for its clinical-stage programs, Luye is developing rotigotine extended-release microspheres for injection for Parkinson’s disease and moderate to severe restless legs syndrome (LY-03003); a serotonin-norepinephrine-dopamine triple reuptake inhibitor (LY-03005) for major depressive disorder for which the FDA accepted an NDA in March 2020; a paliperidone palmitate injectable suspension (LY-03010) for schizophrenia and schizoaffective disorder, extended-release tablets (LY-03012) for chronic pain; and a rivastigmine multiday transdermal patch (LY-30410) for mild to moderate Alzheimer’s disease.