Summary of the interview with the CEO of PaxMedica, a laboratory that is developing the drug SURAMINA for the treatment of autism. Find the full interview here. 

In this webcast, Sarika, the co-founder of the Brain Foundation, interview Howard Weisman, with extensive experience in the pharmaceutical industry, joined the PaxMedica laboratory in 2020 to develop suramin, an old drug that could treat autism. He was inspired by the studies of Professor Naviaux, who found a cellular mechanism involved in autism and demonstrated the positive effects of suramin in 10 children.

Howard explains that autism has to do with a cellular mechanism called purine signaling, which regulates cell defense. Professor Naviaux discovered that suramin could block purine signaling and improve autism symptoms in animals and children. That is what he published and what motivated Michael, the founder of PaxMedica, to investigate suramin.

What were the challenges PaxMedica faced in sourcing suramin?

Suramin is a rare drug used to treat African sleeping sickness caused by a parasite. Michael, the founder of PaxMedica, traveled to Africa to procure suramin for the clinical trial he wanted to run to treat people with autism, he also benefited from a US Congressional program that supports drug development for neglected tropical diseases. Michael was eventually able to obtain suramin to do the clinical trial with children with autism.

FDA approval for suramin and producing it commercially

Howard says in the interview that suramin is used to treat a deadly parasite that causes African sleeping sickness, but that it is very difficult to conduct a clinical trial with this drug because the disease is so rare and deadly. Michael Derby went to the FDA with a team of lawyers and doctors and reached an agreement on how to analyze the data from patients treated with suramin in Africa over the last 20 years. PaxMedica obtained exclusive rights to those medical records through the African governments and continues to collect those records from sleeping sickness hospitals. Those records will be your efficacy study to submit to the FDA. There's a US Congressional program that incentivizes drug development for rare and neglected tropical diseases and gives US market exclusivity to the first company to bring that molecule to the US Howard says he thinks that's the quickest route to getting suramin approved for any use. He also mentions that he is working on producing suramin commercially, since it is currently only produced by the Bayer laboratory on behalf of the WHO every few years. Howard says this will be the world's first commercial supply of suramin.

How is a phase two clinical trial in autism conducted during a pandemic?

Weisman explained that he was drawn to the project because he was impressed by the vision and determination of Dr. Robert Naviaux, the study's principal investigator, who had discovered a possible link between autism and cellular metabolism. 

However, just as Weisman joined PaxMedica as CEO, the COVID-19 pandemic struck the world and put the trial at risk. They managed to recruit two-thirds of the patients before South Africa entered its first lockdown, giving them an advantage. For three months, they were unable to recruit more patients or follow up on those already in the study. Some patients had to be excluded because they were unable to complete the trial due to blocking.

They were lucky that South Africa reopened in August or September 2020 and they were able to recruit the rest of the patients and even a few more to make up for the losses. For them, it was key to have a local team of doctors and researchers who knew the context and the risks well. Despite the difficulties, they managed to finish the trial and obtain promising results on the efficacy and safety of the drug.

Weisman called the study one of the success stories of the pandemic and said he was proud of the work done by PaxMedica and its partners. He also expressed his hope that the findings could be replicated and scaled up in other countries and with other patient groups.

What dose and what frequency are the most appropriate to treat autism with an antiparasitic drug?

It built on the previous work of Dr. Robert Naviaux, the study's principal investigator, who had conducted a phase one trial with single doses of suramin and had seen improvements over three to four weeks. Weisman said that in their trial, they decided to try two different doses: half and the same as the one used by Naviaux. They also said they administered the dose every six weeks over a period of 18 weeks.

Weisman said the results were very positive, finding the lower dose more effective than the higher. He also said they learned that suramin has a very long half-life, staying in the body for 30 to 40 days. This means that it can be given less frequently and avoid possible side effects.

Weisman said the side effects were minimal, with only a few instances of irritation at the injection site. It also said that there were no serious adverse effects or changes in laboratory parameters. Weisman said this demonstrated that suramin is a safe and well-tolerated drug for children with autism.

Weisman expressed his satisfaction with the results of the study and said that he hoped to be able to confirm and expand them in other larger trials and in other countries. He also said that he was interested in exploring the potential of suramin to treat other conditions related to cell metabolism, such as chronic fatigue syndrome or Alzheimer's.

What kind of side effects does suramin, an antiparasitic drug being tested to treat autism, have?

Weisman explained that suramin is a drug used to treat sleeping sickness, an infection caused by a parasite that is transmitted by the bite of a tsetse fly. Weisman said suramin is given through an IV and has some known side effects, including a rash that looks like a sunburn, nausea and vomiting. Weisman said these side effects usually occur a few days after the infusion and resolve on their own.

In their trial, they tested two different doses of suramin: 10 milligrams per kilogram and 20 milligrams per kilogram. They found that the lower dose was more effective and had fewer side effects than the higher one. Weisman said there was only one case of rash and one case of nausea in the low-dose group, while in the high-dose group there were about a third of patients who had those side effects.

Most surprising, Weisman said, was that the placebo group also had a third of the patients with a rash and nausea. This made them think that perhaps those side effects were not related to suramin, but to other factors, such as stress or anxiety, Weisman said. This also gave them more confidence in the study results, since there was no way for parents or doctors to know which children had received the drug or what dose.

In addition to measuring autism symptoms with a standard scale, they also used a secondary measure called the Clinical Global Impression Improvement Scale (CGI-I), which assesses the overall change in a patient's condition. Weisman said they found that the low-dose group had a statistically significant improvement from the start of the trial to the end of the trial. Weisman said this told them that suramin had a psychoactive effect, meaning that it changed the children's behavior.

Weisman expressed excitement about the study results, saying they showed suramin to be a safe and effective drug for children with autism. He also said that he wanted to further investigate the mechanism of action of suramin and how it affects cellular metabolism and the immune system.

What types of measures are used to assess the effect of suramin in autism?

He chose to use FDA-accepted and validated instruments to assess the effect of suramin on autism. One of these was the Autism-Adjusted Aberrant Behavior Checklist (ABC-A), which measures five categories: irritability, hyperactivity, stereotyped behavior, social avoidance, and inappropriate speech. Weisman said that this instrument was a reasonable way to track change in a clinical trial because it had previously been used by the FDA to approve other autism drugs.

Weisman said that another instrument he used was the Clinical Global Impression Improvement Scale (CGI-I), which he mentioned earlier. This instrument assesses the overall change in the patient's condition and found a statistically significant improvement in the low-dose suramin group.

Although received some anecdotal reports of changes in children's speech and communication with suramin, he was unable to include them in his analysis because he had no mechanism for doing so. These changes could be real, but they could also be influenced by other factors, such as stress or anxiety. Weisman said that these changes could be observed with more time and with other more specific instruments.

He said he wants the drug approved for infection and autism, and is working with the FDA. He doesn't know if the drug could further improve autism with more doses or time. The drug modulates the cellular danger response and it does not have negative immunological effects.

Weisman explained that the drug suramin has a very different use for autism than it does for human African trypanosomiasis infection, a parasitic disease that affects millions of people in sub-Saharan Africa. To treat this infection, a very high and aggressive dose of the drug is needed to kill the parasite before it enters the brain. To treat autism, a much smaller and more widely spaced dose of the drug is needed to modulate the cellular danger response, a chronic inflammatory state thought to affect brain development and function in autism.

The drug does not completely turn off the cellular danger response, but instead regulates it to restore the balance between inflammation and repair. The drug has a transient and reversible effect, he said, and does not affect the body's ability to defend itself against infection or injury. Weisman said his company is looking to get the best possible effect with the least amount of drug, and that this is something that will evolve with clinical trials.

Weisman explained that to gain FDA approval, PaxMedica has to show that suramin is safe and effective in treating autism, using objective and validated measures. However, he said that this process is not simple, since autism is a heterogeneous and complex disorder, which cannot be captured with a single measure or criterion.

Could suramin be used longer or more often for autism?

Weisman countered that this depends on safety data and clinical trials, but could also be discovered in clinical practice. He explained that suramin has different effects depending on the dose and the use case. To treat sleeping sickness, a very high and aggressive dose of suramin is needed to kill the parasite before it enters the brain. However, to treat autism, a much lower and less frequent dose of suramin is needed to improve behavioral symptoms.

PaxMedica is looking for the optimal dose, one that is effective and safe. The drug has some mild side effects, such as a rash. The side effects of the drug is something they need to study further, but hopefully it will restore the balance between nerve and immune cells. To get FDA approval, they want to get approval for trypanosomiasis infection first, and then for autism.

Weisman acknowledged that the road to approval of the autism drug is long and complex, but he was optimistic and committed to the goal of making PAX-101 accessible for people who need it. “We work almost every day and try to think about how we make sure that we have done as much as possible and speed up the programs,” he said.

Will people with autism be able to access the drug PAX-101 before it is officially approved?

Weisman replied that this was a possibility that he would consider, but that he first had to make sure that he had enough of the drug and enough data to indicate how to use it safely and effectively. In addition, he said his priority was to complete clinical trials for FDA approval, which could take a couple of years. Weisman explained that there are some regulations that allow companies to help families through expanded access or compassionate use after the drug is approved for another indication, such as African sleeping sickness (AHS).

Weisman was aware of the demand and need for PAX-101 in the autism community, saying he wanted to help people access the drug in the safest way possible.

Is it safe and effective to obtain the drug PAX-101 from unauthorized or natural sources?

Weisman discussed the risks of using unverified or natural sources of suramin, saying that I would only trust an FDA approved drug. He said his company was working to produce a quality drug that met safety and efficacy standards. He also talked about ecopipam, another drug that could improve autism, but needs further study. He thanked the autism community for their support and announced a new clinical trial for ecopipam in South Africa.

Ecopipam is a drug that acts on dopamine receptors and could improve autism. The trial will be done in South Africa, with 30 children of different ages and doses. The goal is to find the lowest and most effective dose, and to measure the metabolism and effect of the drug. Weisman said that he hopes to start the trial in the fall and that he appreciated the support of the autism community.

Weisman talked about his plans for ecopipam, saying he wants to do trials in the US and Europe, but will do one in South Africa first, with 30 children of different ages and doses. He said the drug could also be used for Tourette syndrome and obsessive compulsive disorder. He said that his company is financed by the capital markets and that he appreciates the support of the autism community. He said that those interested in the trial can contact his company for his website.

He discussed various aspects related to suramin and autism. He said that the drug is expensive to manufacture, but that they will look for a fair and accessible price. They support expanded use of the drug, but there is a process for it. They are working on another natural product called neuromodin, which might have properties similar to suramin.