The American Academy of Neurology (AAN) held its Annual Meeting from April 22-28, 2022. During the meeting, various stakeholders discussed trends, science, and research within the field of neurology. According to SMA News Today, one presentation focused on data from the Phase 2 TOPAZ clinical trial. This study focused on the safety, efficacy, and tolerability of apitegromab for spinal muscular atrophy (SMA) types 2 and 3. The study, which followed treated patients for over a year, found that apitegromab improved motor function and stabilized the disease for many patients. 

To take a look at some specific results and findings, check out this poster presentation from the AAN Annual Meeting. 

Apitegromab: Findings from the Phase 2 TOPAZ Clinical Trial

To begin, let’s take a look at what apitegromab is. According to biotechnology company Scholar Rock, who is developing apitegromab, the therapy is:

a selective inhibitor of the activation of latent myostatin, with the aim of improving patients’ motor function. Rather than the traditional approach of blocking already-activated, mature myostatin or the receptor, apitegromab selectively targets the precursor (inactive) form to block its activation in the muscle. 

By blocking myostatin, Scholar Rock hopes that apitegromab would contribute to muscle strength and increased muscle function. 

Scholar Rock evaluated the therapy in the Phase 2 TOPAZ study, in which 57 individuals enrolled. Participants were split into three groups:

• Group 1: In this group, individuals were aged 2+. They took Spinraza before turning 5 years old and could not walk. This group received 2mg/kg or 20mg/kg apitegromab in addition to Spinraza during the trial.
• Group 2: Within this group, patients were between the ages of 5-21. Patients were unable to walk and had not started Spinraza until after they turned 5 years old. This group received 20mg/kg apitegromab in addition to Spinraza.
• Group 3: In the final cohort, patients were also between 5-21 years old. However, this group was able to walk. This group only received intravenous apitegromab. 

The Findings

Ultimately, findings from the study concluded that:

• Apitegromab contributed to disease stability, even in those who did not see marked improvements in motor function. Motor function was more stagnant in those with more advanced SMA.
• 59% of those within Group 1 saw improved motor skill function, as did 29% in the second group, as measured by HFMSE scores. Additionally, 31% and 36% respectively saw heightened arm and hand motor function. Approximately 27% of those within Group 3 also saw motor function improvements. 
• The higher apitegromab dosage seemed to confer more benefits than the lower dose. 
• Altogether, apitegromab was relatively safe and well-tolerated. Some adverse reactions did occur, including a cough, UTIs, headache, and a fever. 

These improvements are promising. In the future, Scholar Rock is continuing to evaluate the treatment through the Phase 3 SAPPHIRE study. 

What is Spinal Muscular Atrophy (SMA)?

SMN1 gene mutations cause spinal muscular atrophy (SMA), a rare genetic disorder characterized by mild-to-severe muscle weakness and degeneration. These gene mutations cause the death and degeneration of motor neurons, leading to muscle atrophy and weakness. Altogether, there are multiple forms of SMA. These come with different outcomes and symptoms. For example, SMA type 1 (also known as Werdnig-Hoffman disease) is a severe form diagnosed at or following birth. Symptoms include developmental delay, difficulty breathing and swallowing, and inability to sit or support the head independently. Alternately, SMA type 3 (or Kugelberg-Welander syndrome) usually manifests between early childhood and adolescence, causing motor delays, as well as difficulty walking. 

To get a full overview of SMA and its subtypes, head here.