Ionis Pharmaceuticals, Inc. is a
biotechnology
Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used b ...
company based in
Carlsbad, California
Carlsbad is a coastal city in the North County region of San Diego County, California, United States. The city is south of downtown Los Angeles and north of downtown San Diego. As of the 2020 census, the population of the city was 114,746. ...
, that specializes in discovering and developing
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
-targeted therapeutics. The company has 3 commercially approved medicines: Spinraza (
Nusinersen
Nusinersen, marketed as Spinraza, is a medication used in treating spinal muscular atrophy (SMA), a rare neuromuscular disorder. In December 2016, it became the first approved drug used in treating this disorder.
Since the condition it treats i ...
), Tegsedi (
Inotersen), and Waylivra (
Volanesorsen) and has 4 drugs in pivotal studies: tominersen for
Huntington’s disease
Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...
, tofersen for SOD1-
ALS
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most com ...
, AKCEA-APO(a)-LRx for
cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
, and AKCEA-TTR-LRx for all forms of TTR
amyloidosis
Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight ...
.
[
The company was named Isis Pharmaceuticals until December 2015.]
History
The company was founded in 1989 as Isis Pharmaceuticals by Stanley T. Crooke, a former head of research of GlaxoSmithKline
GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...
, with a goal to commercialize antisense therapy
Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre-m ...
.
In 1992, the company received its first approval by the Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
for an investigational new drug application in 1992 for a genital warts
Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV). They are generally pink in color and project out from the surface of the skin. Usually they cause few symptoms, but can occasionally be pai ...
drug candidate. The FDA approval marked the first time for the company to conduct any antisense therapy
Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre-m ...
and to be tested in humans.
In 1995, the genital warts
Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV). They are generally pink in color and project out from the surface of the skin. Usually they cause few symptoms, but can occasionally be pai ...
drug failed in clinical trials and Isis terminated development. By that time, Gilead Sciences
Gilead Sciences, Inc. () is an American biopharmaceutical company headquartered in Foster City, California, that focuses on researching and developing antiviral drugs used in the treatment of HIV/AIDS, hepatitis B, hepatitis C, influenza, and CO ...
and Genta had left the antisense therapy field, leaving only Isis, Hybridon, and Lynx Therapeutics working in the field. Gilead sold its patents, developed around antisense, to Isis.
In December 2015, Isis changed its name to Ionis, driven in part by the negative image of "Isis" generated by the terrorist group, Islamic State of Iraq and the Levant
An Islamic state is a State (polity), state that has a form of government based on sharia, Islamic law (sharia). As a term, it has been used to describe various historical Polity, polities and theories of governance in the Islamic world. As a t ...
, commonly known as ISIL or ISIS.[
In 2017, the company completed the corporate spin-off of its rare lipid disorder subsidiary, Akcea Therapeutics.
]
Products
The company's first marketed drug was fomivirsen
Fomivirsen (brand name Vitravene) is an antisense antiviral drug that was used in the treatment of cytomegalovirus retinitis (CMV) in immunocompromised patients, including those with AIDS. It was administered via intraocular injection.
It was d ...
(Vitravene, used in the treatment of cytomegalovirus retinitis
Cytomegalovirus retinitis, also known as CMV retinitis, is an inflammation of the retina of the eye that can lead to blindness. Caused by human cytomegalovirus, it occurs predominantly in people whose immune system has been compromised, 15-40% of ...
(CMV) in immunocompromised patients. It was discovered at the NIH and was licensed and initially developed by Isis, which subsequently licensed it to Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
. It was approved by the FDA for CMV in Aug 1998 as the first antisense drug. Novartis withdrew the marketing authorization for fomivirsen in the EU in 2002 and in the US in 2006. The drug was withdrawn as the development of HAART
The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multip ...
dramatically reduced the number of cases of CMV rinitis.[
The antisense field anticipated that the approval of fomivirsen marked the beginning of a new age of antisense drug treatments that would be similar to the uptake of ]monoclonal antibody therapy
Monoclonal antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAbs) to bind monospecifically to certain cells or proteins. The objective is that this treatment will stimulate the patient's immune system to attack those ...
, but the next FDA approval of an antisense drug came in 2013.[ Part of what held up all companies in the field was the way that the ]oligomers
In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relative ...
were chemically modified to prevent hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
also reduced affinity to the antisense molecules' targets
''Targets'' is a 1968 American crime thriller film directed by Peter Bogdanovich, produced by Roger Corman, and written by Polly Platt and Bogdanovich, with cinematography by László Kovács.Stephen Jacobs, ''Boris Karloff: More Than a Monster' ...
; by 2004 the field was shifting to second generation modifications. Clinical trials of antisense therapeutics by all the companies in the early 2000s were also plagued by lack of efficacy and immune reactions to drug candidates.[ Isis cut its workforce by 40% in 2005 due to weak sales of fomivirsen and lack of confidence by the market in antisense technology.
In 2007, Isis and ]Alnylam Pharmaceuticals
Alnylam Pharmaceuticals, Inc. is an American biopharmaceutical company focused on the discovery, development and commercialization of RNA interference (RNAi) therapeutics for genetically defined diseases. The company was founded in 2002 and is he ...
, which focuses on RNA interference
RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by o ...
, formed a 50/50 joint venture, Regulus Therapeutics
Regulus Therapeutics Inc. or Regulus () is a clinical stage biopharmaceutical company focused on the development of first-in-class drugs that target microRNAs to treat a broad range of diseases. Regulus was established in September 2007 by Alnylam ...
, to apply their intellectual property and knowledge around oligomer biotherapeutics to micro-RNA targets.
In 2008, Isis and Genzyme
Genzyme was an American biotechnology company based in Cambridge, Massachusetts. Since its acquisition in 2011, Genzyme (also known as Genzyme Transgenics Corp or GTC Biotherapeutics) has been a fully owned subsidiary of Sanofi. In 2010, Genzyme ...
entered into a partnered drug candidate mipomersen (Kynamro), intended to treat homozygous familial hypercholesterolemia, and other drug candidates ; the deal included Genzyme buying $150 million of Isis stock and paying a $175 million license fee, as well as milestone fees and royalties. Mipomersen was rejected by the European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
in 2012 and again in 2013; it was approved by the FDA in 2013.[ In January 2016, Ionis terminated its arrangement with Genzyme, stating that the drug had been poorly marketed. In May 2016, Ionis licensed the rights to the drug to Kastle Therapeutics for $15 million upfront with another $10 million due in May 2019, up to $70 million in milestones based on sales, and royalties, with Ionis paying 3% royalty and 3% of non-cash royalty it receives to Genzyme. Mipomersen has still not been approved in Europe.][
In December 2016, Ionis' drug ]nusinersen
Nusinersen, marketed as Spinraza, is a medication used in treating spinal muscular atrophy (SMA), a rare neuromuscular disorder. In December 2016, it became the first approved drug used in treating this disorder.
Since the condition it treats i ...
(Spinraza) was approved by the FDA. It had been discovered in a collaboration between Adrian Krainer at Cold Spring Harbor Laboratory
Cold Spring Harbor Laboratory (CSHL) is a private, non-profit institution with research programs focusing on cancer, neuroscience, plant biology, genomics, and quantitative biology.
It is one of 68 institutions supported by the Cancer Centers ...
and Ionis (then Isis) and preclinical work was done at University of Massachusetts
The University of Massachusetts is the five-campus public university system and the only public research system in the Commonwealth of Massachusetts. The university system includes five campuses (Amherst, Boston, Dartmouth, Lowell, and a medica ...
. The drug was initially developed by Ionis, which partnered with Biogen
Biogen Inc. is an American multinational biotechnology company based in Cambridge, Massachusetts, specializing in the discovery, development, and delivery of therapies for the treatment of neurological diseases to patients worldwide.
History
...
on development starting in 2012; in 2015 Biogen acquired an exclusive license to the drug for a $75 million license fee, milestone payments up to $150M, and tiered royalties between 10 and 15% thereafter; Biogen also paid for all development subsequent to taking the license. The license to Biogen included licenses to intellectual property that Ionis had acquired from Cold Spring Harbor and University of Massachusetts.
As of December 2016, Ionis had ten candidates for various liver disease
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Signs and symptoms
Some of the sig ...
s in clinical trials and a drug it discovered, alicaforsen
Alicaforsen (trade name Camligo) is an antisense oligonucleotide therapeutic that targets the messenger RNA for the production of human ICAM-1 receptor and is being developed for the treatment of acute disease flares in moderate to severe Inflamm ...
, was in a Phase III trial run by another company.[ It also had a ]huntingtin
Huntingtin (Htt) is the protein coded for in humans by the ''HTT'' gene, also known as the ''IT15'' ("interesting transcript 15") gene. Mutated ''HTT'' is the cause of Huntington's disease (HD), and has been investigated for this role and also for ...
gene-lowering antisense molecule for Huntington's disease in clinical trial.
References
External links
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{{Authority control
Biotechnology companies of the United States
Biotechnology companies established in 1989
Huntington's disease
Spinal muscular atrophy
Antisense RNA
Health care companies based in California
Companies based in Carlsbad, California
Companies listed on the Nasdaq