Oligonucleotide‐Based Drugs and Therapeutics Preclinical and Clinical Considerations for Development by Nicolay Ferrari and Rosanne Seguin Ebook PDF
Oligonucleotide‐Based Drugs and Therapeutics Preclinical and Clinical Considerations for Development by Nicolay Ferrari and Rosanne Seguin Ebook PDF Development of oligonucleotide (ODN)‐based therapeutics is being progressed for a wide range of indications and using various routes of administration.
There is a diversity of structures, chemistries, and mechanisms of actions for ODN therapeutics, but most of the members of this class of drug candidates
can be categorized on the basis of whether they target either mRNA or pro-
teins. ODN‐based therapy is distinct from gene therapy as it does not involve
the modification of genes. Antisense ODN (ASO), short interfering RNA
(siRNA), antagomirs, microRNA mimetics, and DNAzymes are part of the
RNA‐targeting group, while immunostimulatory sequences (ISS), aptamers, and decoys are members of the protein‐targeting group.Currently, six ODN‐based pharmaceuticals, including four ASO, have achieved marketing authorization in Europe and/or United States, and many more are undergoing late‐stage clinical testing. The first ASO drug, VITRAVENE (fomivirsen, Ionis Pharmaceuticals – formerly Isis), was approved in 1998 to treat CMV eye infections in HIV patients but within a few years was rendered obsolete by advances in antiretroviral cocktails for HIV therapy.
The field waited 15 years for another approval. In 2013, the second ASO drug, KYNAMRO (mipomersen, Ionis Pharmaceuticals), was approved by the Food and Drug Administration (FDA) for the treatment of familial hypercholester-
olemia. In 2016, out of 22 new drugs approved by FDA, 3 were for ODN thera-
peutics: DEFITELIO (defibrotide, Jazz Pharmaceuticals), a treatment for
veno‐occlusive disease of the liver in individuals who have undergone bone
marrow transplants granted in March; EXONDYS 51 (eteplirsen, Sarepta
Therapeutics), a treatment for Duchenne muscular dystrophy granted in
August; and SPINRAZA (nusinersen, Biogen), a treatment for spinal muscular
atrophy granted in December. In addition, Atlantic Pharmaceuticals is devel-
oping alicaforsen, an ASO targeting ICAM‐1 for the treatment of pouchitis,
and currently supplies alicaforsen in response to physicians’ requests under
international named patient supply regulations for patients with inflammatory bowel disease.