Apitegromab Clinical Trial Updates Expected This Year

Patient enrollment continues in Europe, US for Phase 3 SAPPHIRE trial

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The ongoing SAPPHIRE clinical trial testing apitegromab, Scholar Rock’s investigational muscle-directed therapy, in people with spinal muscular atrophy (SMA) is expected to complete patient enrollment later this year, the company announced.

Top-line data from the trial are anticipated in 2024. Should results be positive, Scholar Rock expects to initiate a commercial product launch in 2025.

The Phase 3 trial SAPPHIRE (NCT05156320) is recruiting up to 204 patients with SMA types 2 or 3 who are unable to walk (nonambulatory), but can sit independently. Enrollment is ongoing at 37 sites across the U.S. and Europe.

Also expected in the first half of this year are three-year extension data from the Phase 2 TOPAZ trial (NCT03921528) of apitegromab, following positive two-year data announced last year.

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“We are excited by the potential coming from our highly differentiated platform … as we advance our spinal muscular atrophy and oncology programs to address critical unmet needs for patients,” Jay Backstrom, MD, president and CEO of Scholar Rock, said in a press release.

“In 2023, we see continued momentum for our growing pipeline,” Backstrom added.

Myostatin is a protein found in skeletal muscles — those involved in coordinating voluntary movements. It works to suppress muscle growth, a process that helps maintain proper muscle mass.

Apitegromab is a lab-made antibody designed to bind to myostatin’s precursor molecule, preventing its conversion into mature myostatin. By reducing levels of mature myostatin, Scholar Rock believes the treatment will increase muscle mass and improve motor function in SMA patients, potentially working as an add-on to other approved SMA therapies.

The TOPAZ trial

The open-label, proof-of-concept TOPAZ trial was designed to test the treatment’s safety and effectiveness in children and young adults, ages 2–21, with SMA types 2 or type 3.

Participants were divided into three groups and received into-the-vein infusions of apitegromab once every four weeks for up to a year in the main trial.

The first group included patients, ages 2 and older, who could not walk and began treatment with Spinraza (nusinersen) before age 5. This group was given apitegromab (2 or 20 mg/kg) as an add-on to Spinraza.

Group 2 enrolled patients, 5–21, who could not walk and started on Spinraza after age 5, while those in group 3, also ages 5–21, retained their walking ability. Both of these groups were given apitegromab (20 mg/kg), usually as an add-on to Spinraza.

Top-line trial results showed that after a year of treatment, motor function was stable in most patients, in contrast to the progressive declines usually seen in these SMA types. Some patients, particularly those who were younger when starting treatment, experienced clinically meaningful improvements.

All 57 people who finished TOPAZ elected to enter its trial extension phase, in which all patients continued to receive apitegromab. Two-year trial data, involving 55 people, showed that motor function had remained stable or further improved.

Additional analyses showed that the treatment also generally led to stabilizations or improvements in measures of fatigue and life quality.

All but one of those 55 people opted to continue a third year of treatment, with 51 still enrolled as of Dec. 31, according to Scholar Rock. A three-year update on these patients is anticipated this year, and TOPAZ is expected to finish in April 2024.

Different doses of apitegromab

The SAPPHIRE trial, designed to confirm TOPAZ results in nonambulatory patients, is testing two does of apitegromab (10 or 20 mg/kg) versus a placebo. Participants will receive their assigned therapy for one year as an add-on to stable treatment with Spinraza or Evrysdi (risdiplam).

The trial’s main goal is to determine changes in motor function, as assessed with the Hammersmith Functional Motor Scale Expanded (HFMSE). Secondary outcome measures include changes in upper limb function, number of motor milestones attained, and myostatin levels.

The development of antibodies against the therapy and other safety measures also will be assessed.