[Publish Date: 02/12/2021]
Results from a new double-blind placebo controlled trial testing suramin in autism in South Africa have been released and like the prior Naviaux suramin trial that N of One backed, the data look very promising suggesting we may indeed have a breakthrough! What's more is that there are now TWO players racing to develop suramin.
Below we summarize the results from this trial, run by PaxMedica, and provide analysis of what this latest development means.
What was the trial?
The trial was a double-blind, placebo-controlled randomized trial (the gold-standard in medicine). Subjects received either 3 doses of suramin (1 every 4 weeks) at one of two different dose levels or a placebo. Subjects likely were evaluated all along the trial, but PaxMedica only specifically says they were evaluated 6 weeks after their last dose (which would be week 14). They were evaluated using a number of commonly used autism diagnostic behavioral tests, including the ADOS, which Dr. Naviaux used in his initial trial.
What were the results?
PaxMedica is reporting* a 48% improvement in the ABC-core, a broad-based measure of multiple autism symptoms vs. a 31% improvement for the placebo group. Note: they do not state whether this was statistically significant, though that would a reasonable assumption. They also claim positive "sustained" (read: at the 14 week mark) improvements in other diagnostic tests including: Clinical Global Impressions (CGI-I) and Autism Treatment Evaluation Checklist (ATEC).
What about Safety?
This was the first time that suramin has been given in multiple doses so safety is/was a prime concern. As a reminder, Dr. Naviaux only had approval to use a single dose (infusion) of suramin on the first N of One backed, SAT-1 trial.
The company reports that the drug was well-tolerated for the duration of the trial. Of the originally 52 enrolled, 9 dropped (5 due to COVID-19 lockdowns, 1 for an adverse event, and 2 other unspecified reasons). The most common side-effects were rash (which suramin is known to often produce), upper respiratory infection and vomiting. There was one serious unspecified adverse event (presumably the drop-out) that resolved following acute treatment.
Analysis of Safety and Efficacy
On the surface this all looks very encouraging. PaxMedica's end points are broad-based and widely used autism measures. They used quite a lot of measurement tools, but only spoke of improvements in some, so presumably they may have not achieved improvements in all their end-points, such as ADOS. However, they did issue this caveat - "This trial .[ ]..was not powered to demonstrate statistical significance across endpoints." So it's possible they had improvements in some endpoints, but did not have enough subjects enrolled to be able to definitively say that it was not due to chance.
The safety profile looks very encouraging, especially given all early concerns about suramin's potential toxicity. I think one can look past the covid drop outs and the one adverse-event related drop out is quite good for a study of this size.
Who is PaxMedica?
Neither I nor Dr. Naviaux have had any interaction with PaxMedica. From their website, they appear to be a small team of experienced drug developers who are attempting to build on Dr. Naviaux's published results.
What is PaxMedica Doing?
They are taking a very creative, though unorthodox approach of trying to get US FDA approval for suramin for an unrelated condition, African Sleeping Sickness or "HAT" which is non-existent in the United States. What is unorthodox about their approach is that they are attempting to do this without ever running a trial, but instead by using data obtained in Africa. If successful, they would be eligible for a rare disease priority voucher, which they could re-sell, but more importantly, as the first to obtain approval for suramin in the US for any condition, they will be afforded special market exclusivity for suramin. This may pose serious challenge for Kuzani.
Who is Kuzani?
Glad you asked. Kuzani is another company that has been working on developing suramin for autism over the past several years. Unlike the thinly-funded PaxMedica, Kuzani is backed by the deep pocketed Morningside Group and has been working with Dr. Naviaux for several years. Kuzani was scheduled to begin a multi-center suramin-autism trial in 2020 but that was delayed due to covid. That trial will hopefully begin sometime in 2021.
A Foot Race
My sense is that there is not room for two players developing the same drug for the same indication. PaxMedica clearly has the upper-hand at this point in the regulatory realm with actual human clinical data and a potential near-term approval for HAT.
However, since Bayer has historically been unwilling to provide suramin to groups trying to develop it for autism, manufacturing is going to become a critical bottleneck and in this department I give the edge to the better-funded Kuzani who has been working on this for much longer.
How does all this shake out? We will have to wait and see but the critical thing to watch will be if PaxMedica gets it's HAT approval. If so, I suspect there will need to be a "negotiation" between the two companies.
My suspicion is that these companies both operated in such stealth mode that neither was aware of the other until each was relatively far along.
Stepping back a bit, the fact that there are now two companies aggressively competing to develop suramin for autism is good news for our children. I caught up with Dr. Naviaux about the recent PaxMedica announcement and thought he summed it up well:
"The PaxMedica results, if confirmed in larger studies, are very encouraging and suggest we are entering an era of renewed hope for children and adults with ASD. I’m excited to see our research on autism, suramin and the CDR is having ripple effects around the world."
The race is on. Let's hope our kids are the winners!
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*Important disclaimer - The company has provided limited information so far about its trial. The following is analysis based on what they have publicly provided and could change. Paxmedica's full press release is available here