Full Press Release Details
Positive Top Line Results from the PAX-101 (intravenous suramin) Phase 3 African Sleeping Sickness Study, PAX-HAT-301
- The study's primary endpoint was reached and demonstrated statistically significant and clinically meaningful results
- These results pave the way for filing an NDA for the use of PAX-101 (intravenous suramin) for the treatment of African Sleeping Sickness
TARRYTOWN, NY, July 24, 2023 - PaxMedica,
Inc. (Nasdaq: PXMD), a clinical stage biopharmaceutical company focusing on the development of novel anti-purinergic drug therapies (APT)
for the treatment of Autism Spectrum Disorder (ASD) and other serious conditions with intractable neurologic symptoms, today 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.
Howard Weisman, Chief Executive Officer of PaxMedica,
commented, "We're excited to have completed this important real world evidence study that demonstrated both statistically
significant and clinically meaningful results, and confirmed over 100 years of clinical experience with suramin as a life-saving medication
in this potentially fatal infection. Completion of this study is an important step on the path to bring suramin to the United States under
the Neglected Rare Tropical Disease Program and will enable PaxMedica to accelerate the clinical development of PAX-101 for the treatment
of the core symptoms of ASD."
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
Background Information
Human African Trypanosomiasis (HAT), also known
as sleeping sickness, is caused by infection with vector-borne protozoan parasites of the two species of Trypanosoma brucei: Trypanosoma
brucei gambiense and Trypanosoma brucei rhodesiense (TBR). TBR HAT is an acute form of HAT with the symptoms emerging within weeks, and
death occurring within six months, if untreated. Between 1900 and 1920, an epidemic of the disease occurred in Uganda resulting in the
death of an estimated 250,000 people. At the time of the epidemic, there were no known treatments. Physicians tried to treat patients
with arsenic, and some arsenic-related compounds, with limited success and significant side effects.
Suramin was introduced in 1922 and is still frequently
used as first-line treatment for Stage 1 TBR HAT. Suramin is unsuitable for use in confirmed Stage 2 TBR HAT because it does not readily
cross the blood-brain barrier. It has been manufactured by Bayer and distributed to countries endemic for TBR HAT through the World Health
Organization. Suramin was never approved for use in the U.S. or EU, and it is difficult to procure quickly, although it is often prescribed
to US travelers who contract TBR HAT after a trip to an endemic area in Africa.
PaxMedica is a clinical stage biopharmaceutical
company focusing on the development of anti-purinergic drug therapies ("APT") for the treatment of disorders with intractable
neurologic symptoms, ranging from neurodevelopmental disorders, including Autism Spectrum Disorder ("ASD"), to Myalgic Encephalomyelitis/Chronic
Fatigue Syndrome ("ME/CFS"), a debilitating physical and cognitive disorder. One of PaxMedica's primary points of focus
is the development and testing of its lead program, PAX-101, an intravenous formulation of suramin, in the treatment of ASD and the advancing
the clinical understanding of using that agent against other disorders such as ME/CFS.
For more information, visit www.paxmedica.com.
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