RNA Interference Therapy-Competitive landscape, 2023

This “RNA Interference Therapy - Competitive landscape, 2023” report provides comprehensive insights about 40+ companies and 90+ drugs in RNA Interference Therapy Competitive landscape. It covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

Geography Covered

• Global coverage

RNA Interference Therapy: Understanding

RNA Interference Therapy: Overview

RNA interference (RNAi) is one of the pathways, collectively named RNA silencing pathways that employ small RNAs as guides for sequence-specific silencing. RNAi was discovered in C. elegans and defined as sequence-specific mRNA degradation induced by long double-stranded RNA (dsRNA). The RNA interference (RNAi) pathway regulates mRNA stability and translation in nearly all human cells.

RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is a conserved biological response to double-stranded RNA that mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes. This natural mechanism for sequence-specific gene silencing promises to revolutionize experimental biology and may have important practical applications in functional genomics, therapeutic intervention, agriculture and other areas.

Development of new therapeutics is a constant battle for successful, safe, clinical trials that maintain clinical efficacy. Small-molecule drugs were traditionally the solution for all diseases until the development of monoclonal antibody therapy. Monoclonal antibody therapy has been successful for many diseases, but still incurs difficulties with tissue penetration, manufacturing, and purification. RNA interference (RNAi) therapeutics provide alternative treatment options when current drug technology fails. Additionally, therapeutics for infectious diseases are quickly obsolete owing to mutational escape. Development of RNAi strategies addresses both needs; thus, it may be the next technology to revolutionize the drug market.

Therapeutically, RNAi works via delivery of small RNA duplexes, including microRNA (miRNA) mimics, short interfering RNAs (siRNAs), short hairpin RNAs (shRNAs), and Dicer substrate RNAs (dsiRNAs). As a therapeutic, all four types of RNAi inputs are currently in clinical trials. Major considerations include toxicity, efficacy, and delivery. RNAi therapeutic toxicity occurs via improper target recognition or immunogenic effects from exogenously introduced RNA, in addition to any toxic effects due to delivery methodology.

Fast progress in RNAi technology has shown promise for use in reverse genetics and therapy. However, mechanistic complexities of this technology still need to be determined. RNAi has now been established as a revolutionary tool for functional genomics in organisms. Multiple studies have defined the role of RNAi in mammalian and plant defense systems. A plethora of studies have utilized RNAi technology to modulate gene expression. RNAi-based full genomic screens have allowed identification of specific genes, controlling a given trait with high accuracy.

RNA interference is a highly conserved biological mechanism that responds to pathogenic viral dsRNA to mount an inhibitory molecular response. Many studies have shown that RNAi can be used therapeutically to target many respiratory viruses in vitro and in vivo, including SARS-CoV and potentially SARS-CoV-2, in the treatment and prevention of infection. More research is needed both at the basic and clinical settings before such therapies are made routine.

Report Highlights

• In March 2023, Alnylam Pharmaceuticals, Inc., the leading RNAi therapeutics company, and Medison Pharma, a global pharma company focused on providing access to highly innovative therapies for patients in international markets, announced an expansion of their existing partnership to a multi-regional agreement that includes Poland, Czech Republic, Hungary, Slovakia, Lithuania, Estonia and Latvia, in addition to Israel.
• In July 2021, Arbutus Biopharma Corporation and Vaccitech entered into a clinical trial collaboration agreement to evaluate an innovative therapeutic combination for the treatment of subjects with chronic hepatitis B virus (HBV) infection (CHB) who are already receiving standard-of-care nucleos(t)ide reverse transcriptase inhibitor (NrtI) therapy.
• In December 2021, Arbutus Biopharma Corporation and Qilu Pharmaceutical, entered into an exclusive licensing agreement and strategic partnership for the development and commercialization of AB-729 for the treatment or prevention of hepatitis B in mainland China, Hong Kong, Macau and Taiwan.
• In November 2021, Arrowhead Pharmaceuticals Inc. announced that its collaborator, Janssen Pharmaceuticals, Inc., (Janssen) one of the Janssen Pharmaceutical Companies of Johnson & Johnson, has disclosed its collaboration with Arrowhead on investigational compound JNJ-75220795, which is in a Phase 1 clinical study.
• In August 2020, Assembly Biosciences and Arbutus Biopharma Corporation, entered into a clinical collaboration agreement to evaluate Assembly's lead hepatitis B virus (HBV) core inhibitor candidate ABI-H0731 in combination with Arbutus' proprietary GalNAc delivered RNAi therapeutic AB-729 and standard-of-care nucleos(t)ide reverse transcriptase inhibitor (NrtI) therapy for the treatment of patients with chronic HBV infection. As part of the collaboration, the companies may add cohorts in the future, to evaluate other patient populations and/or combinations.
• In April 2018, Regeneron Pharmaceuticals and Alnylam Pharmaceuticals announced a collaboration to discover, develop and commercialize new RNA interference (RNAi) therapeutics for a broad range of diseases by addressing disease targets expressed in the eye and central nervous system (CNS), in addition to a select number of targets expressed in the liver.

RNA Interference Therapy: Company and Product Profiles (Marketed Therapies)

1. Company Overview: Biogen/Ionis Pharmaceuticals

Biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological, autoimmune and rare diseases. Founded in 1978, Biogen is one of the world's oldest independent biotechnology companies and patients worldwide benefit from its leading multiple sclerosis and innovative hemophilia therapies.

Product Description: Nusinersen

Nusinersen is an antisense oligonucleotide (ASO) that is designed to alter the splicing of SMN2, a gene that is nearly identical to SMN1, in order to increase production of fully functional SMN protein. ASOs are short synthetic strings of nucleotides designed to selectively bind to target RNA and regulate gene expression.Through use of this technology, nusinersen has the potential to increase the amount of functional SMN protein in infants and children with SMA.

In December 2016, Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced that the U.S. Food and Drug Administration (FDA) approved SPINRAZATM (nusinersen) under Priority Review for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients. SPINRAZA is the first and only treatment approved in the U.S. for SMA, a leading genetic cause of death in infants and toddlers that is marked by progressive, debilitating muscle weakness. SPINRAZA was discovered and developed by Ionis and Biogen, and licensed to Biogen who is responsible for future development, manufacturing, and commercialization of SPINRAZA.

2. Company Overview: Novartis AG

Novartis is reimagining medicine to improve and extend people's lives. It delivers high-value medicines that alleviate society's greatest disease burdens through technology leadership in R&D and novel access approaches. In the quest to find new medicines, the company consistently rank among the world's top companies investing in research and development. About 108,000 people of more than 140 nationalities work together to bring Novartis products to nearly 800 million people around the world.

Product Description: Leqvio

Leqvio is the first and only small interfering RNA (siRNA) therapy to lower low-density lipoprotein cholesterol (also known as bad cholesterol or LDL-C) with two doses a year, after an initial dose and one at three months. Leqvio is indicated in the United States as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. The effect of Leqvio on cardiovascular morbidity and mortality is being explored in clinical trials currently underway.

In December 2021, Novartis announced that the US Food and Drug Administration (FDA) approved Leqvio® (inclisiran) for primary hyperlipidemia (including heterozygous familial hypercholesterolemia). Leqvio is approved in more than 60 countries worldwide, including the US, and the EU. Novartis has obtained global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals, a leader in RNAi therapeutics.

RNA Interference Therapy: Company and Product Profiles (Pipeline Therapies)

1. Company Overview: Alnylam Pharmaceuticals, Inc

Alnylam has led the translation of RNAi (RNA interference) from Nobel Prize-winning discovery into an innovative, entirely new class of medicines. Founded in 2002 by a team of distinguished life sciences leaders, Alnylam's vision is to harness the potential of RNAi therapeutics to transform the lives of people living with diseases for which there are limited or inadequate treatment options. The pioneering work of the company has delivered the world's first and only approved RNAi therapeutics - ONPATTRO® (patisiran) in 2018, GIVLAARI® (givosiran) in 2019, OXLUMO® (lumasiran) in 2020, and AMVUTTRA® (vutrisiran) in 2022. It is advancing a deep pipeline of innovative RNAi-based medicines in four therapeutic areas: genetic medicines, cardio-metabolic diseases, infectious diseases, and central nervous system (CNS) and ocular diseases.

Product Description: Cemdisiran

Cemdisiran is an investigational RNAi therapeutic targeting the C5 component of the complement pathway in development for the treatment of complement-mediated diseases. The complement system plays a central role in immunity as a protective mechanism for host defense, but its dysregulation results in life-threatening complications in a broad range of human diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic-uremic syndrome (aHUS), myasthenia gravis, neuromyelitis optica, and membranous nephropathy, amongst others.

In April 2018, Regeneron Pharmaceuticals and Alnylam Pharmaceuticals announced a collaboration to discover, develop and commercialize new RNA interference (RNAi) therapeutics for a broad range of diseases by addressing disease targets expressed in the eye and central nervous system (CNS), in addition to a select number of targets expressed in the liver. Alnylam's partner Regeneron initiated Phase III studies of cemdisiran and pozelimab combination in myasthenia gravis and paroxysmal nocturnal hemoglobinuria.

2. Company Overview: Arrowhead Pharmaceuticals, Inc.

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead's RNAi-based therapeutics leverage this natural pathway of gene silencing.

Arrowhead is focused on developing innovative drugs for diseases with a genetic basis, characterized by the overproduction of one or more proteins. The depth and versatility of our RNAi technologies enable us to address conditions in virtually any therapeutic area and pursue disease targets that are not otherwise druggable by small molecules and biologics.

Product Description: ARO-APOC3

ARO-APOC3 is a subcutaneously administered RNAi therapeutic designed to reduce the production of Apolipoprotein C-III (Apoc-III), a component of triglyceride-rich lipoproteins (TRLs) including VLDL and chylomicrons, and is a key regulator of triglyceride metabolism. The company believes that knocking down the hepatic production of Apoc-III may result in reduced VLDL synthesis and assembly, enhanced breakdown of TRLs, and better clearance of VLDL and chylomicron remnants. It is currently being developed as a potential treatment for patients with severe hypertriglyceridemia (SHTG), familial chylomicronemia syndrome (FCS), and mixed dyslipidemia.

Arrowhead's investigational RNA interference (RNAi) therapeutic is currently under Phase III trial for Familial Chylomicronemia and Phase II for mixed Dyslipidemia and SHTG. Furthermore, Arrowhead has successfully completed the Phase I trial for Hypertriglyceridemia and FCS. In June 2019, Arrowhead Pharmaceuticals received U.S. Food and Drug Administration (FDA) orphan drug designation for ARO-APOC3 in the treatment of FCS.

3. Company Overview: Vir Biotechnology

Vir Biotechnology is a commercial-stage immunology company focused on combining immunologic insights with cutting-edge technologies to treat and prevent serious infectious diseases. Vir has assembled four technology platforms that are designed to stimulate and enhance the immune system by exploiting critical observations of natural immune processes. Its current development pipeline consists of product candidates targeting COVID-19, hepatitis B and hepatitis D viruses, influenza A and human immunodeficiency virus.

Product Description: VIR-2218

VIR-2218 (ALN-HBV02) is a subcutaneously administered, investigational RNAi therapeutic targeting the Hepatitis B virus (HBV) genome for the treatment of chronic HBV infection by Alnylam collaborators at Vir Biotechnology. ALN-HBV02 is designed to inhibit expression of all HBV proteins, including hepatitis B surface antigen (HBsAg). ALN-HBV02 utilizes Enhanced Stabilization Chemistry-Plus (ESC+)-GalNAc delivery platform. Vir presented results from the Phase II study of ALN-HBV02, showing a positive safety profile and reduction of hepatitis B surface antigen. Brii Bio and Vir Biotechnology have agreed to commence clinical development efforts in China for VIR-2218.

4. Company Overview: Akamis Bio

Arbutus Biopharma Corporation is a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop novel therapeutics that target specific viral diseases. The current focus areas include Hepatitis B virus (HBV), SARS-CoV-2, and other coronaviruses. To address HBV, the company is developing a RNAi therapeutic, an oral PD-L1 inhibitor, and an oral RNA destabilizer to potentially identify a combination regimen with the aim of providing a functional cure for patients with chronic HBV by suppressing viral replication, reducing surface antigen and reawakening the immune system. In addition, the company also have an ongoing drug discovery and development program directed to identifying novel, orally active agents for treating coronavirus (including SARS-CoV-2).

Product Description: AB-729

AB-729 is a subcutaneously-delivered RNA interference (RNAi) therapeutic specifically designed to reduce all HBV viral antigens, including hepatitis B surface antigen, which is thought to be a key prerequisite to enable reawakening of a patient's immune system to respond to the virus. AB-729 targets hepatocytes using novel covalently conjugated N-acetylgalactosamine (GalNAc) delivery technology. Clinical data generated thus far has shown single- and multi-doses of AB-729 to be generally safe and well-tolerated, while also providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. AB-729 is currently in multiple Phase II clinical trials.

RNA Interference Therapy Analytical Perspective

In-depth Commercial Assessment: RNA Interference Therapy Collaboration Analysis by Companies

The Report provides in-depth commercial assessment of drugs that have been included, which comprises collaboration, agreement, licensing and acquisition - deals values trends. The sub-segmentation is described in the report which provide company-company collaboration (licensing/partnering), company academic collaboration and acquisition analysis in tabulated form.

RNA Interference Therapy Competitive Landscape

The report comprises of comparative assessment of Companies (by therapy, development stage, and technology).

RNA Interference Therapy Report Assessment

• Company Analysis
• Therapeutic Assessment
• Pipeline Assessment
• Inactive drugs assessment
• Unmet Needs

Key Questions Answered

Current Treatment Scenario and Emerging Therapies:

• How many companies are developing RNA Interference Therapy drugs?
• How many RNA Interference Therapy drugs are developed by each company?
• How many emerging drugs are in mid-stage, and late-stage of development for the treatment of RNA Interference Therapy?
• What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the RNA Interference Therapy therapeutics?
• What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies?
• What are the clinical studies going on for RNA Interference Therapy and their status?
• What are the key designations that have been granted to the emerging and approved drugs?

Key Players

• Silence Therapeutics
• Janssen Research & Development
• Eli Lilly and Company
• Arrowhead Pharmaceuticals
• Sylentis
• Sirnaomics
• Dicerna Pharmaceuticals
• Suzhou Ribo Life Science
• Alnylam Pharmaceuticals
• Suzhou Ribo Life Science
• Vir Biotechnology
• Arbutus Biopharma
• Silenseed
• OliX Pharmaceuticals
• Bio-Path Holdings

Key Products

• SLN124
• JNJ-75220795
• LY3819469
• ARO-HIF2
• SYL 1801
• STP707
• DRC-AUD
• SLN360
• Cemdisiran
• ARO-APOC3
• DCR-PHXC
• SYL-1001
• Fitusiran
• Zilebesiran
• VIR-2218
• AB 729
• Antisense K-ras RNA gene therapy
• OLX 101A
• Lumasiran
• Prexigebersen-A

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