Sarepta Therapeutics has announced data through week 120 from Study 202, a phase IIb open-label extension study of Eteplirsen in patients with Duchenne muscular dystrophy ( DMD ). Results through more than two years showed a continued stabilization of walking ability in Eteplirsen-treated patients evaluable on the 6-minute walk test ( 6MWT ). As previously reported, Study 202 met its primary endpoint of increased novel dystrophin as assessed by muscle biopsy at week 48 and is now in the long-term extension phase in which patients continue to be followed for safety and clinical outcomes.
At 120 weeks, patients in the 30 mg/kg and 50 mg/kg Eteplirsen cohorts who were able to perform the 6MWT ( modified intent-to-treat or mITT population; n=6 ) experienced a decline of 13.9 meters, or less than 5%, from baseline in walking ability.
A statistically significant treatment benefit of 64.9 meters ( p less-than or equal to 0.006 ) was observed for the mITT population compared with the placebo/delayed-treatment cohort ( n=4 ), which initiated treatment at week 25 following 24 weeks of placebo. After experiencing a substantial decline earlier in the study, the placebo/delayed-treatment cohort also demonstrated stabilization in walking ability for more than 1.5 years, from week 36 through 120, the period from which meaningful levels of dystrophin were likely produced, with a decline of 9.5 meters over this timeframe. These analyses were based on the maximum 6MWT score when the test was performed on two consecutive days.
Through 120 weeks, Eteplirsen was well tolerated and there were no reported clinically significant treatment-related adverse events and no treatment-related serious adverse events. In addition, there were no treatment-related hospitalizations or discontinuations.
Duchenne muscular dystrophy is an X-linked rare degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. One of the most common fatal genetic disorders, Duchenne muscular dystrophy affects approximately one in every 3,500 boys born worldwide.
A devastating and incurable muscle-wasting disease, Duchenne muscular dystrophy is associated with specific errors in the gene that codes for dystrophin, a protein that plays a key structural role in muscle fiber function. Progressive muscle weakness in the lower limbs spreads to the arms, neck and other areas. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and death usually occurs before the age of 30.
Eteplirsen is designed to address the underlying cause of Duchenne muscular dystrophy by enabling the production of a functional dystrophin protein. Data from clinical studies of Eteplirsen in DMD patients have demonstrated a broadly favorable safety and tolerability profile and restoration of dystrophin protein expression.
Eteplirsen uses phosphorodiamidate morpholino oligomer ( PMO )-based chemistry and exon-skipping technology to skip exon 51 of the dystrophin gene enabling the repair of specific genetic mutations that affect approximately 13% of the total DMD population.
By skipping exon 51, Eteplirsen may restore the gene's ability to make a shorter, but still functional, form of dystrophin from messenger RNA, or mRNA. Promoting the synthesis of a truncated dystrophin protein is intended to stabilize or significantly slow the disease process and prolong and improve the quality of life for patients with DMD. ( Xagena )
Source: Sarepta Therapeutics, 2014