Anvisa publishes study on polylaminin, an innovative drug for spinal cord injuries at UFRJ; to understand

The objective is now to evaluate a commercial formulation of the drug, carried out in partnership with the Cristália laboratory, which will sponsor the studies. According to the agency, this first phase will involve 5 volunteers, aged 18 to 72, who suffered complete lesions of the thoracic spinal cord between the T2 and T10 vertebrae, with surgical indication, less than 72 hours ago. Patients with chronic injuries will therefore not be eligible.

The objective of the first phase will be to evaluate the safety of polylaminin, observing the potential risks and side effects of its application. The research locations remain to be defined. Depending on the results, the drug may move on to phases 2 and 3, which aim to prove its effectiveness in treating the injury. Only after completing all three steps can the drug be submitted for approval to Anvisa for use.

However, the head of the Extracellular Matrices Biology Laboratory, at the Institute of Biomedical Sciences of the UFRJ, and project manager, Tatiana Sampaio, recalls that provisional release before phase 3 may be a possibility due to the characteristics of a rare, very serious injury, without alternative treatment today:

— I believe that this first stage will begin within a month and will be rapid, because it only concerns 5 patients. And recruiting patients shouldn’t take long because the study is getting a lot of publicity. Doctors will therefore be vigilant to inform them of this possibility. I expect that we will start phase 2 probably in less than a year and, if it shows good results, that we could obtain exceptional authorization for use before phase 3.

The request to start clinical studies on humans was submitted at the end of 2022. Since then, Anvisa’s technical team has organized meetings and advised the laboratory to adjust the request and meet all regulatory requirements to conduct clinical research in the country.

The documentation was based on preliminary tests, in the so-called preclinical phase, carried out in the laboratory, with animal models and human patients, some of whom recovered their movements after administration of the drug. However, these tests only serve to demonstrate the potential of the drug and are not enough to prove its effectiveness and make it usable – for this, clinical studies are necessary.

However, since the existence of polylamine became known, patients with spinal cord injuries have gone to court and obtained favorable decisions forcing UFRJ researchers to apply the experimental substance due to the severity of their pathology. Tatiana explains that she respected the court decisions, but considers that these requests are not part of the research protocol and hinder the conduct of the studies:

—What was happening was that people were going to court to demand execution and we had to do it. But we couldn’t track people, provide the best support, or collect the data Anvisa needs. We were using an investigational drug without the protection of a clinical trial. Anvisa’s approval is a relief as it will now allow us to channel our efforts into generating the necessary data within research protocols.

Polylaminin began to be developed 27 years ago and is made from a protein isolated from the placenta called laminin. Among its functions is the regeneration of axons, neuronal structures that are damaged in the event of spinal cord injury, affecting communication between the brain and muscles.

In preliminary tests, polylamine was evaluated in dogs and a group of 8 human volunteers, treated between 2018 and 2021 in the acute phase, up to 72 hours after injury. The application was made directly to the spinal cord during surgery. Results were varied, with some patients having complete recovery of movement and others having partial improvement.

Now, in the clinical study, an injectable formulation of 100 μg/mL laminin will be used, which needs to be diluted before use to obtain polylaminin. This process, called polymerization, binds smaller molecules into a larger structure, increasing their potency. The medication will be administered once intramedullarily, directly to the injured area.

In October, after meeting with Tatiana, the Minister of Health, Alexandre Padilha, had already declared that the ministry and Anvisa had established a priority for studies on the drug. Now, the agency’s approval has been granted under Anvisa’s Innovation Committee, established last year to facilitate regulatory assessment of products and technologies considered innovative.