お知らせ • Jul 25
PaxMedica, Inc. Announces Positive Top Line Results from the PAX-101 (intravenous suramin) Phase 3 African Sleeping Sickness Study, PAX-HAT-301
PaxMedica, Inc. announced positive top line data for the Company’s PAX-HAT-301 Retrospective Analysis of Suramin Treatment for Stage 1 Trypanosoma Brucei Rhodesiense Human African Trypanosomiasis (S1 TBR HAT). The conclusions of the study confirmed that the retrospective, non-randomized, externally controlled, interventional efficacy and safety study of suramin for the treatment of Stage 1 TBR HAT demonstrated better health outcomes when compared with a natural history control group of patients evaluated and treated from 1900-1910, prior to the availability of suramin in Africa. The adverse event profile of suramin observed in the study was consistent with what has been widely reported in published medical and clinical literature. PaxMedica is expecting to file an NDA with the U.S. Food and Drug Administration (FDA) for the use of PAX-101 to treat Stage 1 African Sleeping Sickness (also known as Human African Trypanosomiasis Brucei Rhodesiense or TBR HAT), in 2024. If approved, suramin will be the first drug indicated for the treatment of TBR HAT in the United States, and would potentially qualify PaxMedica to receive a Priority Review Voucher (PRV) under the Neglected Rare Tropical Disease Program in section 524 of the Food, Drug, and Cosmetics Act (FD&C Act). A PRV, once granted, is an independently valued asset (see GAO report 20-251), granted to a sponsor company after NDA approval and, according to section b(2) of the act, can be sold by that sponsor to any biopharmaceutical company, to obtain FDA priority review in a future filing of any NDA. The PAX-HAT-301 Study: The PAX-HAT-301 study is a retrospective, non-randomized, externally controlled, interventional efficacy and safety study comparing medical records data from a cohort of patients with Stage 1 Trypanosoma Brucei Rhodesiense (S1 TBR HAT) evaluated and treated from about 2000 – 2020 at one medical site in Uganda and two medical sites in Malawi (referred to as the suramin-treated cohort), with medical records data from a cohort of patients from 1900-1910 evaluated and treated during the TBR HAT epidemic in Uganda (referred to as the natural history cohort). These records included data from a few weeks of hospitalization while they were being evaluated and the diagnosis of TBR HAT confirmed. As their conditions began to deteriorate, patients were often treated with arsenic or related compounds, sent to a Sleeping Sickness Hospital, or sent home to die with their families. The natural history records do not include long term outcomes data for many of the patients. The study was designed in consultation with the U.S. Food and Drug Administration (FDA) and to ensure that the historical control group of patients had TBR HAT (not the chronic TBG form) and were in Stage 1 of the disease. The primary objective of the study was to determine whether standard of care treatment with suramin, as currently practiced in Uganda and Malawi, from 2000-2020, led to better health outcomes in patients with S1 TBR HAT, than outcomes observed in a natural history cohort from the epidemic >100 years ago. The secondary objective was to evaluate the safety and tolerability of suramin. The primary endpoint of the study was survival and not meeting any of the supportive descriptive criteria (i.e., death, progression of the disease from Stage 1 to Stage 2, or becoming “moribund” [discharged to a sleeping sickness hospital, physician or patient giving up hope, or being close to death with no hope of recovery]). An independent study adjudication committee was established to review the suramin-treated and natural history cases for study eligibility, and to confirm the clinical endpoints. The committee was comprised of three physicians experienced in the treatment of TBR HAT in Malawi and Uganda. The PAX-HAT-301 Study Results: The outcomes observed in the suramin-treated cohort were both statistically significant and clinically meaningfully different from the outcomes observed in the natural history cohort. The suramin-treated patients had a far lower rate of death or progression to Stage 2 compared with the natural history cohort. In addition, many of the longer-term outcomes from the natural history cohort pointed towards death as the inevitable outcome of TBR HAT without the benefit of suramin treatment. In the study population there were 349 patients, 145 in the suramin-treated cohort and 204 patients in the natural history cohort. There were 121 suramin-treated and 42 natural history patients with sufficient data and that met all eligibility criteria for the primary analysis. The suramin-treated patients had a mean age of 31.1 years (range from 2 to 85 years) and 64% male. The natural history patients had a mean age of 22 (range from 3 to 40 years) and 79% male. Racial and ethnicity data were not available and weight was only available for about half of the suramin-treated patients. The suramin-treated patients presented with a variety of commonly reported HAT related symptoms. The most common symptoms were fever/chills, severe headache, aching joints, extreme fatigue, and swollen lymph nodes. The natural history cohort patients had presenting symptoms recorded in 27/42 (64%) of cases. The reported symptoms were similar including headache, “feeling ill”, drowsiness, cough, weakness, chest pain, diarrhea, and enlarged lymph nodes. One suramin-treated patient tested positive for HIV (only 23% tested) and 16/76 (21%) of patients tested were positive for malaria. No comparable data is available for the natural history cohort. The outcomes for the two cohorts differed substantially. Of the suramin patients, 114 (94%) survived and successfully completed the treatment. Three patients (2%) had “Other” listed as the reason for stopping suramin treatment and 4 (3%) had no reason for stopping suramin treatment recorded. No patients required rescue medications for progression from Stage 1 to Stage 2. In the natural history cohort, 6 (14%) were recorded as cured, improved, or discharged. Three (7%) patients died, 10 (24%) experienced clinical worsening, and 17 (40%) achieved moribund status (near death and in terminal clinical decline). It is anticipated that if all of these patients were followed for up to 6 months, that nearly all of them would have died. The primary efficacy analysis revealed that the health outcomes in the suramin-treated cohort were statistically significantly better than those in the natural history cohort. According to the definition of the primary endpoint, the proportion of patients in the suramin-treated group that was alive and not meeting any supportive descriptive criteria of death, any clinical worsening or moribund status was 92% vs. 50% in the natural history cohort. The estimated proportion (95% CI) was 0.442 (0.277, 0.600). The two-sided p-value for the Fisher’s exact test was <0.001.