Apitegromab Trial Data Show Motor Function Improvement in Non-Ambulatory People who have SMA Types 2 and 3

23 June 2022

Apitegromab Trial Data Show Motor Function Improvement in Non-Ambulatory People who have SMA Types 2 and 3

Apitegromab phase 2 trial (TOPAZ) extension data, presented at the recent Cure SMA Research & Clinical Care Meeting last week, supported sustained and continued motor function improvement for non-ambulatory people living with SMA Types 2 and 3 and receiving an SMN-enhancement therapy.
 

About Apitegromab and its phase 2 (TOPAZ) trial

Apitegromab is a muscle-directed therapy that aims to reverse or restrict the muscle atrophy and weakness experienced by people living with SMA. The drug is an antibody that very specifically targets an important protein called myostatin, currently trialled in two studies: TOPAZ and SAPPHIRE.

The TOPAZ trial is a phase 2 study designed to evaluate the safety and efficacy of apitegromab in a broad range (aged 2 to 21 years old) of people living with SMA Types 2 and 3. Participants were divided into three cohorts:

  • Cohort 1: people with SMA Type 3 who are able to walk (some also on Spinraza™)
     
  • Cohort 2: people with SMA Type 2 or 3 who are not able to walk and who are on Spinraza™
     
  • Cohort 3: people with SMA Type 2 SMA and on Spinraza™

In the main treatment period, participants were dosed intravenously every four weeks with apitegromab alone or with nusinersen (Spinraza™), an approved SMN therapy. The trial enrolled 58 participants, both in Europe and the U.S.

The primary efficacy endpoints were mean change from baseline in motor function tests at 12 months for participants who are able to walk (Cohort 1) and mean change from baseline in motor function tests at 12 months for participants who are not able to walk (Cohorts 2 and 3). The trial also includes multiple 12-month extension periods designed to evaluate longer-term outcomes.
 

The Results

The results of the TOPAZ  trial extension period evaluating outcomes after 24-months of treatment show:

  • Substantial increase in motor function of participants with SMA Types 2 and 3 who are not able to walk (cohorts 2 & 3) and are receiving an SMN therapy (Spinraza™)
     
  • Stabilisation of motor function scores in people living with SMA Type 3 who are able to walk (cohort 1) and are receiving an SMN therapy (Spinraza™)
     
  • No serious safety risks over 24 months

The incidence and severity of adverse events were consistent with the underlying patient population and background therapy. The five most common treatment-emergent adverse events (TEAEs) were headache, fever, upper respiratory tract infection, cough, and nasopharyngitis (inflammation of the nasal passages and throat). No deaths or serious adverse reactions have been observed with apitegromab. A total of 14 serious TEAEs have been reported over the 24-month treatment period, all assessed by the respective trial investigator as unrelated to apitegromab.

Of the 55 patients who completed the 24-month TOPAZ extension period, 54 have opted to continue treatment in the 36-month extension period.
 

Conclusion

Underscoring the 12 month TOPAZ trial findings, the 24-month results provide long-term data and evidence that participants receiving apitegromab experienced sizable motor function gains. This continued increase in motor function support the transformative potential of apitegromab for people living with SMA.
 

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