FDA BRIEF: Week of September 19, 2016

EXONDYS 51 (eteplirsen) injection

Sarepta Therapeutics, Cambridge, MA, USA  

INDICATION: Treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping.

A clinical benefit of EXONDYS 51 has not been established. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.


  • Duchenne muscular dystrophy (DMD) is a rare and devastating disease
  • Occurs in 1 out of every 3,600 male infants worldwide
  • Progressive muscle deterioration and weakness; most common type of muscular dystrophy
  • Need for an approved treatment


  • Accelerated Approval
  • However, FDA internal Scientific Dispute on Approval between CDER Review Division and CDER Director
  • Key disagreement on the amount of dystrophin protein produced in sufficient to be ‘reasonably likely’ to predict clinical benefit.
  • FDA Commissioner deferred to CDER Director’s assessment of granting accelerated approval
  • Sponsor required to conduct a clinical trial to  to assess whether Exondys 51 improves motor function of DMD patients with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping.
  • If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug.

FDA Commissioner Memo

MECHANISM OF ACTION: Accelerated approval based on an increase in dystrophin in skeletal muscle observed in some patients treated with EXONDYS 51.  Eteplirsen  binds to exon 51 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.


  • 3 clinical studies, patients with confirmed mutation of DMD gene amenable to exon 51 skipping, Exondys vs,. placebo, or open label
  • Primary Endpoint: dystrophin production
  • Clinical outcome measure: 6-minute walk test (6MWT)
  • No significant difference in change in 6MWT for EXONDYS 51 vs. placebo (Study 1)
  • Not possible to estimate dystrophin production in response to EXONDYS 51 (Study 2)
  • Dystrophin level: Pretreatment level 0.16% ± 0.12%  of level in healthy subject vs. and 0.44% ± 0.43% after 48 weeks of EXONDYS 51 (p < 0.05).

SAFETY: Most common side effect: Balance disorder and vomiting.


 AMJEVITA (adalimumab-atto)

INDICATION: In adult patients with

  • moderately to severely active rheumatoid arthritis;
  • active psoriatic arthritis;
  • active ankylosing spondylitis (an arthritis that affects the spine);
  • moderately to severely active Crohn’s disease;
  • moderately to severely active ulcerative colitis; and
  • moderate to severe plaque psoriasis.

Also indicated for moderately to severely active polyarticular juvenile idiopathic arthritis in patients four years of age and older.

REG PATHWAY: Biosimilar to Humira®


  • Structural and Functional characterization
  • Animal study data
  • Human Pharmacokinetic and Pharmacodynamics data
  • Clinical immunogenicity data
  • Other clinical safety and effectiveness data


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