ANTISENSE OLIGONUCLEOTIDE THERAPEUTICS

Given the multifaceted advantages of antisense oligonucleotide therapeutics, the field has witnessed an increase in the number of players involved in the development of such solutions. The domain features the presence of over 30 companies which are involved in the development of over 170 antisense oligonucleotide drugs.

Majority of the developers (55%) of antisense oligonucleotide therapeutics are start-ups or small-sized (less than 50 employees), followed by 29% large (501-5000 employees) and 16% mid-sized companies (51-500 employees). Notable examples of the start-ups in the antisense oligonucleotide domain include (in alphabetical order) Atlantic Healthcare, Dynacure, Isarna Therapeutics, and Sterna Biologicals.

Majority of the antisense oligonucleotide therapeutics (81%) are single stranded DNA, which are complementary to the mRNA target.  Examples of antisense DNA molecules include (in alphabetical order) AKCEA-APOCIII-LRx (Ionis Pharmaceuticals), Casimersen (Sarepta Therapeutics) and Tominersen (Hoffman-La Roche). Further, nearly 20% of the antisense oligonucleotides are RNA molecules. Moreover, nearly half of the antisense oligonucleotide therapeutics are second-generation molecules. These therapies have been developed to overcome the challenges of the first-generation therapeutics, such as poor binding affinity and adverse side effects.

Additionally, it is worth highlighting that seven molecules (capturing 4% of the share), namely, Spinraza (by Ionis Pharmaceuticals), Vyondys 53 (Sarepta Therapeutics), Tegsedi (Ionis Pharmaceuticals), Waylivra (Ionis Pharmaceuticals), Viltepso (Nippon Shinyaku) and Exondys 51 (Sarepta Therapeutics) have been commercialized till date and over 60% molecules are currently in advanced stages of development (phase II and above). In addition, majority of the therapies (28) are designed for administration through subcutaneous route. The subcutaneous route of administration facilitates rapid onset of the therapeutic action that can be extended to a longer duration. Examples of late stage molecules that are being administered subcutaneously include (in alphabetical order) ATL1102 (Antisense Therapeutics), IONIS-FB-LRx (Ionis Pharmaceuticals) and Pelacarsen (Novartis). Further, the second most preferred route of administration is intravenous route. This route of delivery gives reproducible effects and the administered dose directly reaches systemic circulation.

Status of Academic Grants that have been Granted in the Next Generation Immune Checkpoint Inhibitors and Stimulators Domain

Over the past few years, several non-profit organizations have extended financial support to aid the research related to antisense oligonucleotide therapeutics. This chapter provides information on the various academic grants awarded by the National Institutes of Health (NIH), and its sister organizations, for projects related to antisense oligonucleotides.

Over the past few years, grants worth USD 307 million have been awarded to various organizations working in this domain during time period between January 2017 to September 2020. It is worth mentioning that in 2020, University of Iowa received the highest grant amount of USD 7.13 million for a project (project number: 5U01NS055903-11). The grant was awarded to support the research activity in order to study striatal-cerebellar circuitry in children that are at high risk of Huntington's Disease.

Further, more than 30% of the grants awarded to support research related to the antisense oligonucleotide projects were / are being managed by NINDS. This is followed by grants managed by NHLBI (12%) and NCI (11%) in the given time period. Other active administrating institutes include NIA (7%), NIAID (6%) and NIDDK (5%). Additionally, it is worth mentioning that majority of the grants (413) were awarded to the projects associated with the established therapeutic areas, namely genetics, neurological and oncology. Of these, genetics has received the maximum grants (187).  It is worth highlighting that close to 50 grants have been inclined to each spinal muscular atrophy and myotonic dystrophy underneath this focus area.  In addition, USD 34 million and USD 30.5 million have been granted to these indications, respectively.  Further, close to 100 grants are awarded to some emerging therapeutic areas, such as metabolic, infectious, cardiovascular, and hematological.

The Hype Number of Clinical Trials Associated with Antisense Oligonucleotides is Evident of the Growing Potential of the Domain

Over the Years

The field of antisense oligonucleotide therapeutics has witnessed a continuous increase in the number of trials registered per year, representing a CAGR of ~21% between 2010 and 2019. This can be attributed to the continuous increase in the initiatives being taken by several industry and non-industry players that are actively evaluating the therapeutic effectiveness of antisense oligonucleotide based therapies for a wide range of indications. Interestingly, the maximum number of trials (134) were initiated post 2014; of these, nearly 30% have been initiated in 2019 and 2020.

There has been a continuous increase in the number of patients enrolled in the trials related to antisense oligonucleotide therapies, representing a CAGR of 30% between 2010 and 2019. Overall, 17,133 patients have been enrolled in the trials registered till October 2020. Further, 37% clinical trials that have been / are being conducted to evaluate the therapeutic potential of different types of antisense oligonucleotides are phase II studies. It is worth mentioning that more than 70% (of the total number of patients enrolled) patients are enrolled in phase II and phase III clinical trials.

The Hype Number of Clinical Trials Associated with Antisense Oligonucleotides is Evident of the Growing Potential of the Domain

Over the Years

The field of antisense oligonucleotide therapeutics has witnessed a continuous increase in the number of trials registered per year, representing a CAGR of ~21% between 2010 and 2019. This can be attributed to the continuous increase in the initiatives being taken by several industry and non-industry players that are actively evaluating the therapeutic effectiveness of antisense oligonucleotide based therapies for a wide range of indications. Interestingly, the maximum number of trials (134) were initiated post 2014; of these, nearly 30% have been initiated in 2019 and 2020.

There has been a continuous increase in the number of patients enrolled in the trials related to antisense oligonucleotide therapies, representing a CAGR of 30% between 2010 and 2019. Overall, 17,133 patients have been enrolled in the trials registered till October 2020. Further, 37% clinical trials that have been / are being conducted to evaluate the therapeutic potential of different types of antisense oligonucleotides are phase II studies. It is worth mentioning that more than 70% (of the total number of patients enrolled) patients are enrolled in phase II and phase III clinical trials.

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