60 Degrees Pharmaceuticals has reported encouraging clinical and molecular findings from an expanded access study evaluating tafenoquine-containing combination treatments in immunosuppressed patients with relapsing babesiosis. All five patients who completed treatment reported substantial improvement and tested negative for Babesia parasites using conventional polymerase chain reaction testing, while four also tested negative using a more sensitive molecular assay after treatment. The findings suggest that tafenoquine combined with atovaquone-containing regimens could offer a potential treatment approach for patients with persistent infections, although the small uncontrolled study cannot establish definitive cure or treatment superiority.
The Nasdaq-listed pharmaceutical company is continuing to evaluate the investigational approach while preparing for a separate randomized study readout expected in January 2027. The results could inform discussions with the U.S. Food and Drug Administration about a potential regulatory pathway for tafenoquine in babesiosis, a tick-borne infection that can become particularly difficult to treat in patients with weakened immune systems.
What did the tafenoquine expanded access study reveal about relapsing babesiosis treatment?
The open-label, multicenter expanded access study, registered as NCT06478641, is evaluating tafenoquine alongside atovaquone and other antimicrobial medications in patients with relapsing babesiosis and risk factors for severe disease. Five participants had completed treatment and undergone follow-up assessments when the company reported its latest findings. All five described their clinical condition as much improved or very much improved, indicating substantial perceived recovery following treatment.
Each participant also had a negative conventional PCR test for Babesia documented during treatment or subsequent follow-up. PCR testing detects genetic material from the parasite and can help identify persistent infections that may not be visible using standard microscopy. More sensitive testing provided an additional measure of treatment response. Four of the five patients, representing 80%, had nonreactive results on a blood-donor nucleic acid amplification test performed after completing treatment.
The remaining patient tested positive using the sensitive assay despite having a negative conventional PCR result. This discrepancy demonstrates why the method used to evaluate parasite clearance is particularly important when determining whether infection has been eliminated. Two additional patients remained on treatment, bringing total enrollment to seven. The expanded access study remains open while the company considers further discussions with the FDA.
Although the findings are encouraging, the study lacks a randomized comparison group and involves multiple medications administered together. Consequently, the available evidence cannot establish how much of the observed improvement was attributable specifically to tafenoquine.
Why is babesiosis particularly dangerous for immunocompromised patients with persistent infections?
Babesiosis is a tick-borne infectious disease caused by Babesia parasites that invade and multiply inside red blood cells. The infection can produce fever, chills, sweating, fatigue and muscle or joint discomfort, although disease severity varies considerably among patients.
Individuals with healthy immune systems may recover without developing serious complications. However, patients with impaired immune function, certain cancers, organ transplants or absent or poorly functioning spleens face a greater risk of severe or prolonged infection.
In these vulnerable populations, Babesia parasites can remain detectable or reappear after treatment. Persistent infection may cause ongoing symptoms, blood cell destruction and other potentially life-threatening complications.
The clinical challenge is especially significant because parasite levels can become too low to detect through routine blood-smear microscopy while the infection remains present. Patients may appear to be recovering even though enough parasites survive to cause another episode.
Previous research has highlighted the seriousness of relapsing babesiosis in patients with impaired immune defenses. A 2008 study reported three deaths among 14 patients with persistent or relapsing infection, while a larger 2025 multicenter analysis found higher mortality among immunocompromised patients and those with impaired splenic function than among immune-intact patients. These findings illustrate the need for more effective approaches to treating difficult infections and confirming whether parasites have been eliminated.
Currently, commonly used babesiosis treatment regimens include atovaquone combined with azithromycin, while other antimicrobial combinations may be considered in severe or persistent cases. Highly immunocompromised patients can require treatment for substantially longer periods than individuals with uncomplicated infection.
How does sensitive NAT testing differ from conventional PCR in detecting Babesia parasites?
One of the distinctive features of the expanded access study is its use of sensitive molecular testing after treatment has ended. The treatment protocol requires tafenoquine-containing therapy to continue until patients have experienced resolution of babesiosis symptoms and achieved two consecutive negative conventional PCR results. Treatment then continues for another two weeks before discontinuation.
Investigators subsequently collect blood samples for testing with a nucleic acid amplification assay originally designed to screen donated blood for Babesia contamination. According to 60 Degrees Pharmaceuticals, this blood-donor NAT assay is approximately 500 times more sensitive than the conventional PCR methods used in routine clinical monitoring.
Samples from the five completed participants were obtained between 66 and 120 days after tafenoquine treatment ended. This interval provides an opportunity to assess whether parasite genetic material remains detectable after patients have stopped receiving the investigational regimen.
The four negative NAT results are encouraging because they suggest that circulating parasite levels had fallen below the assay’s detection limit. Nevertheless, a negative blood test does not guarantee that all parasites have been eliminated from every location in the body.
The positive NAT finding in the remaining participant also highlights an important limitation of relying exclusively on conventional PCR. A patient may test negative using one method while a more sensitive assay continues detecting evidence of infection.
The company believes that sustained NAT nonreactivity could serve as a useful marker of treatment success. However, whether this result reliably predicts freedom from future relapse has not yet been established through sufficiently large prospective studies.
What do earlier tafenoquine studies suggest about sustained recovery from relapsing babesiosis?
60 Degrees Pharmaceuticals also analyzed previously published cases involving patients treated with tafenoquine and atovaquone-containing combinations for persistent or relapsing babesiosis. Across seven reported patients, six remained free from additional babesiosis treatment for at least 12 weeks after completing therapy. This represented an observed retreatment-free proportion of 85.7%.
The company compared those outcomes with a model-estimated retreatment-free proportion of 23.5% for conventional treatment approaches, accounting for factors such as treatment duration, accompanying medications and previous therapeutic history. The resulting exploratory comparison suggested a statistically significant association, with a reported p-value of 0.019. However, this was not a randomized comparison, and the modeled reference group cannot substitute for a contemporaneous control arm.
Published case reports may also be subject to selection and reporting biases, particularly when favorable treatment experiences are more likely to receive attention. The findings therefore support further investigation rather than establishing that tafenoquine combinations produce higher cure rates than standard therapy.
An additional limitation concerns the interpretation of retreatment-free survival. Remaining without further treatment for 12 weeks is an encouraging indicator of sustained response, but it does not necessarily establish permanent parasite eradication. Longer follow-up will be necessary to determine whether patients remain free from relapse over time, especially those whose immune suppression persists.
Could 60 Degrees Pharmaceuticals seek accelerated FDA approval for tafenoquine in babesiosis?
60 Degrees Pharmaceuticals is considering a regulatory strategy that could involve accelerated approval if its application relies primarily on data from immunosuppressed patients with relapsing babesiosis. Under this proposed approach, the company would ask the FDA to consider post-treatment NAT nonreactivity as a surrogate endpoint reasonably likely to predict durable clinical benefit.
A surrogate endpoint is a laboratory measurement or other indicator used to predict a meaningful treatment outcome. Such endpoints may support accelerated approval in appropriate circumstances, although regulators must determine whether the proposed measurement is sufficiently supported by scientific evidence.
If an accelerated approval pathway were accepted, the company would propose a postmarketing confirmatory study to verify clinical benefit and assess whether negative NAT results reliably predict sustained freedom from relapse. However, the FDA has not agreed that NAT nonreactivity is an acceptable surrogate endpoint for babesiosis treatment, and the company’s proposed approach remains subject to regulatory review.
Tafenoquine is already approved in the United States for malaria prevention under the brand name ARAKODA. That approval does not extend to treating or preventing babesiosis, and clinicians should not interpret the expanded access findings as authorization for a new indication.
The company is also evaluating tafenoquine in a separate randomized, placebo-controlled study involving patients hospitalized for babesiosis. This trial compares tafenoquine or placebo added to standard-of-care treatment, providing a more rigorous framework for assessing potential clinical benefits.
The study’s data safety monitoring board previously recommended continuing without identifying new safety signals during its interim review. However, the trial remains blinded, and its efficacy results are not yet available.
What comes next for the randomized hospitalized babesiosis trial and FDA discussions?
60 Degrees Pharmaceuticals expects to unblind its hospitalized babesiosis study, registered as NCT06207370, in January 2027 and report its primary and secondary endpoint findings. The trial originally targeted enrollment of 33 participants, with 30 enrolled when the company announced its decision to proceed toward unblinding. Management cited the limited additional statistical power from enrolling three more patients and the seasonal nature of babesiosis transmission.
After reviewing the randomized study results, the company intends to request a pre-supplemental New Drug Application meeting with the FDA. Those discussions would address the combined evidence from hospitalized patients, expanded access treatment and published clinical literature. The randomized findings will be particularly important because the current expanded access results cannot isolate tafenoquine’s contribution from the effects of accompanying medications.
Safety evaluation will also remain essential. Tafenoquine is associated with important risks, including hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, making appropriate screening and clinical monitoring necessary when considering its potential use.
For immunocompromised patients experiencing recurrent babesiosis, the reported improvements and negative molecular tests provide encouraging early evidence. However, the findings involve very few patients, include one positive sensitive molecular result and do not establish that treatment prevents future relapse.
The next major question is whether randomized clinical evidence and longer-term follow-up can confirm that tafenoquine-containing regimens improve patient outcomes beyond existing therapeutic approaches. Until those questions are resolved, tafenoquine remains investigational for babesiosis despite its established approval for malaria prevention.
