The board of directors of Simcere Pharmaceutical Group Limited announced that, on January 18, 2024, the New England Journal of Medicine (NEJM, 2022 Impact Factor: 158.5), digitally published the complete data of the Group's phase II/III, double-blind, randomized, placebo-controlled clinical trial (NCT05506176) (the Study) of XIANNUOXIN (Simnotrelvir Tablets/Ritonavir Tablets (co-packaged)), a 3CL oral innovative drug used for the treatment of adult patients with mild-to-moderate COVID-19 (DOI: 10.1056/NEJMoa2301425). From August 19, 2022 to December 16, 2022, a total of 1,208 patients were enrolled at 35 research sites in China, with 603 patients in the XIANNUOXIN group (received 750mg of Simnotrelvir plus 100mg of Ritonavir, twice daily for 5 days) and 605 patients in the placebo group. The results showed that, for adult patients with mild to moderate COVID-19 in China, XIANNUOXIN could accelerate recovery from symptoms, and shorten the duration of the disease cause, reduce viral load rapidly and significantly, and demonstrate good safety and tolerance: Significantly shortened the median time to sustained resolution of 11 targeted COVID-19 symptoms (the Duration), with greater effectiveness in patients with high risk factors: In the modified intention-to-treat 1 (the mITT1) population who received the first dose within 72 hours after COVID-19 symptom onset, XIANNUOXIN could significantly shorten the Duration by 35.8 hours; In the subgroup of patients with risk factors for severe COVID-19, XIANNUOXIN could shorten the Duration by 60.4 hours.

Demonstration of rapid and significant decrease in viral load: in the mITT1 population, the additional change in viral load from baseline in the XIANNUOXIN group was 96.9% (-1.51 log 10 copies/mL) compared with placebo group on day 5. Good safety profile: the safety data showed the XIANNUOXIN group reported a slightly higher occurrences of adverse events than placebo group, most of these events were of mild or moderate severity and could be recovered without any medical intervention, which suggesting that XIANNUOXIN was safe and tolerable. The median age of the patients included in the Study was 35 years, and 1,092 patients (95.9%) had completed primary vaccination, with 874 patients (76.7%) had received a booster dose. Meanwhile, various Omicron variants were covered in the Study, which demonstrated the application value of XIANNUOXIN in clinical practice.

The publication of the Study with great success signifies that XIANNUOXIN has become the first domestically-made 3CL target anti-SARS-CoV-2 drug with a complete evidence chain. Before that, the results of the pre-clinical study, the phase I clinical trial and the phase Ib clinical trial of XIANNUOXIN have been successively published in prestigious academic journals, such as the sub-journals of Lancet and Nature, during the period from July 2023 to October 2023. On October 13, 2023, the discovery process and the pre-clinical study results of Simnotrelvir, the active ingredient of XIANNUOXIN, were digitally published on Nature Communications (DOI:10.1038/s41467-023-42102-y).

On September 30, 2023, the investigation of the phase I clinical study (NCT05339646) results of Simnotrelvir on healthy adults participating into the trial in terms of drug safety, tolerability and pharmacokinetics were digitally published on European Journal of Pharmaceutical Sciences (DOI: 10.1016/j.ejps.2023.106598). On July 11, 2023, the assessment of the phase Ib clinical study (NCT05369676) results of Simnotrelvir-Ritonavir for the treatment of COVID-19 in terms of effectiveness and safety were digitally published on The Lancet Regional Health ­ Western Pacific (DOI: 10.1016/j.lanwpc.2023.100835).