The first RNAi drug patisiran is expected to be available soon

  • Author:Jane
  • Source:ZHIYAO
  • Release on :2017-09-21
Today US biotechnology company Alnylam announced that its RNAi drug patisiran reached a primary, secondary end point in a familial amyloid polyneuropathy (FAP) phase III, which is the first clinical end point for RNAi drugs to be clinically in Phase III clinics. The trial, called Apollo, recruited 225 patients, using 18-month primary end mNIS + 7 and secondary end point NorfolkQoL were significantly reduced, indicating that the drug not only slowed the disease worsening, but also in reversing the disease. The withdrawal rates were 7.4 and 37.7% in the medication and placebo groups, respectively, and the efficacy was significant. The mortality rates were 4.7% and 7.8%, respectively, but did not appear to be statistically significant. The most important thing is that patisiran does not seem to have troubled RNA drug safety problems, of course, the specific data also in November meeting to be announced. Affected by this news ALNY rose 52% today, while rival Ionis fell 9%.

Drug source analysis

FAP is a rare genetic disease, but the onset of late, usually after adult disease. The disease not only seriously affects the quality of life, but also very high fatal, the survival after diagnosis is less than 15 years. Today, this population is a kind of FAP, by the thyrotropin (TTR, a transporter) amyloidosis leading to three-stage structure of the fold error, causing denaturation of protein accumulation in the organization. This disease is difficult to control with traditional drugs, and RNA drugs such as patisiran and Ionis antisense nucleic acid (ASO) drug NEURO-TTR can selectively degrade TTR mRNA to avoid the synthesis of toxic proteins. Of course the emerging protein degradation techniques such as Protac may also treat such diseases in the future.

RNAi was discovered in 1998, the discovery of the Nobel Prize in 2006, which is rare in modern times, today's results be regarded as a bonus to the Nobel Committee. RNAi was used in the study, but it was difficult to clinically transform with other new therapeutic plates such as antibodies, ASO, gene therapy, and cell therapy. Early thought that RNAi selectivity than traditional drugs, and later found high selectivity of RNAi, but have to find carefully. 10 years ago it was pointed out that only the C9-11 sequence was a true specific fragment, and the other 20 nucleotide sequences were poorly specific. However, the biggest technical barrier to RNA drugs is not selective, but the stability, immunogenicity, transmembrane, large-scale production and other traditional drugs are not often encountered problems, as well as derived delivery, security challenges.

Effective chemical modification can solve most of the above problems, but the appropriate dosage form is also important. Patisiran is a liposome dosage form, which is a commonly used technique for targeting liver, but is highly immunogenic and has poor safety. Patisiran, although likely to be the first listed RNAi drug, is likely to be the last liposomal RNA drug. Last year Arrowhead also announced that it would terminate the development of its hydrophobic EX1 delivery system. Now more is a chemical modification called GalNAc, liver targeting is very good, and no intravenous injection, subcutaneous administration can be, IV administration is Patisiran and ASO drug competition is a major disadvantage. PCSK9 RNAi drug Inclisiran is the use of this technology. But this technology is not no problem. Last year ALNY's another FAP drug revusiran was killed in a three-phase clinical death, and this year a hemophilia drug fitusiran was also halted by the death of one person thrombosis.

However, with the new technology in the clinical inevitably encounter all kinds of ups and downs, Merck, Roche, Novartis have quit RNAi, last year GlaxoSmithKline terminated with the Ionis part of the ASO project The Sanofi started working with ALNY in 2014 to develop RNAi now look is quite far-sighted. Recently Novartis to return to the field of ASO, Squibb also acquired some RNA assets. Coupled with last year's SMA drug Nusinersen listing and a number of mRNA, microRNA companies appear in high-profile, this year more RNA-based small molecule drug company Arrakis debut, RNA drugs become the next class of mainstream drugs conditions seem to have begun to mature.