Sarepta Therapeutics

Last updated
Sarepta Therapeutics, Inc.
Company type Public
Founded1980;44 years ago (1980)
Headquarters Cambridge, Massachusetts, U.S.
Key people
Douglas S. Ingram (CEO & president)
RevenueDecrease2.svg US$1.145 billion (2023) [1]
Number of employees
1,314 (December 2023)
Website sarepta.com

Sarepta Therapeutics, Inc. is a medical research and drug development company with corporate offices and research facilities in Cambridge, Massachusetts, United States. Incorporated in 1980 as AntiVirals, [2] shortly before going public the company changed its name from AntiVirals to AVI BioPharma soon with stock symbol AVII and in July 2012 changed name from AVI BioPharma to Sarepta Therapeutics and SRPT respectively. [3] As of 2023, the company has four approved drugs (see the Products section below).

Contents

History

Sarepta started in Corvallis, Oregon on January 1, 1980 and was originally named Antivirals Inc. [4] After occupying several research laboratory spaces in Corvallis, the company opened a production laboratory in Corvallis in February 2002 and was renamed AVI BioPharma Inc. [5] The company made headlines in 2003 when it announced work on treatments for severe acute respiratory syndrome (SARS) and the West Nile virus. [5] [6] In July 2009, the company announced they would move their headquarters from Portland, Oregon, north to Bothell, Washington, near Seattle. [7] At that time, the company led by president and CEO Leslie Hudson had 83 employees and quarterly revenues of $3.2 million. [7] AVI had yet to turn a profit and had not yet developed any commercial products as of July 2009. [7] The company lost $19.7 million in the second quarter of 2009, [8] and then won an $11.5 million contract with the U.S. Department of Defense's Defense Threat Reduction Agency in October 2009. [9] By this time, the company had completed its headquarters move to Bothell. [7] [9]

In 2012, the company moved a second time, to Cambridge, Massachusetts. At the time, CEO Chris Garabedian indicated the move was motivated by the need to recruit expertise in rare diseases. [10] The Corvallis laboratory facility was closed in 2016. The company opened a new Genetic Therapies Center of Excellence in Columbus, Ohio in October, 2021 in order to dramatically advance research into therapeutics for several muscular dystrophies that had begun at Nationwide Children's Hospital several years earlier. [11]

In June 2017, Sarepta Therapeutics appointed former Allergan executive Doug Ingram as its new CEO to replace Edward Kaye who had announced plans to step down earlier that year. [12]

In February 2019, Sarepta acquired five gene therapy candidates for $165 million after one of them, MYO-101, produced results with a new gene therapy candidate for patients with Limb-Girdle muscular dystrophy; two months after receiving a single treatment, muscles from all three patients were producing the protein they couldn't make on their own. [13]

As of 2022, there are three FDA-approved Duchenne muscular dystrophy drugs in Sarepta Therapeutics' portfolio. [14] In January 2023, Sarepta partnered with Catalent to manufacture delandistrogene moxeparvovec (SRP-9001). [15] [16] [17]

In June 2023, the FDA approved Sarepta Therapeutics’ fourth therapy, delandistrogene moxeparvovec-rokl, the first gene therapy to treat Duchenne muscular dystrophy (DMD). The product was approved under the accelerated approval pathway for 4-5 year olds with a confirmed DMD diagnosis. Accelerated approval requires that the product be studied further to verify its clinical benefit. [18]

Products

Its primary products are based on Morpholino oligomers (PMOs), synthetic nucleic acid analogs that were conceived of by James Summerton and invented by Summerton with Dwight Weller, originally developed under the name NeuGene Antisense. Since morpholino oligomers can form sequence-specific double-stranded complexes with RNA they are suitable use in antisense therapy. In one application, translation blocking, a morpholino oligomer binds to messenger RNA produced by a known disease-causing gene to prevent it from being translated into protein. Morpholinos can also work as splice-switching oligos, targeting pre-mRNA to alter splicing and so causing changes in the structure of the mature mRNA (the mechanism of the approved drug eteplirsen). Morpholinos have been tested for a wide range of applications including prevention of cardiac restenosis after angioplasty, treatment of coronary artery bypass grafts, treatment of polycystic kidney disease, redirection of drug metabolism, treatment of some mutations causing Duchenne muscular dystrophy (DMD), and inhibition of infectious diseases. Their greatest clinical and commercial success thus far has been in the treatment of DMD. A new class of Morpholino oligos, the peptide-linked Morpholinos or PPMO, are linked to an arginine-rich cell-penetrating peptide to enhance their delivery into cells and have entered clinical trials [19]

The Morpholino drug eteplirsen, targeting exon 51 of the dystrophin mRNA, was approved as a human therapeutic by the FDA in 2016 [20] and antisense oligonucleotides for Morpholinos targeting other exons are also subsequently approved. [21] Morpholinos have been used in preclinical studies to inhibit replication of a broad range of viruses, including influenza, West Nile virus, SARS, hepatitis C, dengue fever, Ebola and Calicivirus, all of which are single stranded RNA viruses. They are in advanced development for prevention and treatment of Ebola and Marburg viruses. In March 2013, the Company announced positive results from a non-human primate study of AVI-7288, the drug candidate for treatment of Marburg virus infection. The results showed that intramuscular administration of AVI-7288 resulted in survival rates up to 100 percent in monkeys exposed to this fatal virus. These results are similar to those in previous studies when the drug was given by intravenous injection. [22]

In December 2019, golodirsen (Vyondys 53) received US FDA approval [23] for the treatment of cases that can benefit from skipping exon 53 of the dystrophin transcript. The other approved PMO developed by Sarepta is casimersen (AMONDYS45) which is indicated for the treatment of DMD in patients amendable by exon 45 skipping. [24]

In addition to development of Morpholinos as therapeutics, AVI has conducted six human trials for colorectal and pancreatic cancers using their cancer vaccine AVICINE.

In 2019, Sarepta signed a licensing agrement with Roche for the development, and commercialization outside of USA, for SRP-9001. [25] In June 2023, ELEVIDYS (Delandistrogene moxeparvovec) was approved by the FDA for use in 4-5 year old boys with mutations in the DMD gene. [26] [27] [28] The FDA granted accelerated approval to ELEVIDYS, which requires that the product be further studied to verify its clinical benefit. [28] [29]

In June 2024, the U.S. Food and Drug Administration expanded approval of delandistrogene moxeparvovec to include individuals with Duchenne muscular dystrophy with a confirmed mutation in the DMD gene who are at least 4 years of age. The FDA granted traditional approval for non-ambulatory patients and accelerated approval for non-ambulatory patients. [30]

See also

Related Research Articles

<span class="mw-page-title-main">Duchenne muscular dystrophy</span> Type of muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy predominantly affecting boys. The onset of muscle weakness typically begins around age four, with rapid progression. Initially, muscle loss occurs in the thighs and pelvis, extending to the arms, which can lead to difficulties in standing up. By the age of 12, most individuals with Duchenne muscular dystrophy are unable to walk. Affected muscles may appear larger due to an increase in fat content, and scoliosis is common. Some individuals may experience intellectual disability, and females carrying a single copy of the mutated gene may show mild symptoms.

<span class="mw-page-title-main">Morpholino</span> Chemical compound

A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule used in molecular biology to modify gene expression. Its molecular structure contains DNA bases attached to a backbone of methylenemorpholine rings linked through phosphorodiamidate groups. Morpholinos block access of other molecules to small specific sequences of the base-pairing surfaces of ribonucleic acid (RNA). Morpholinos are used as research tools for reverse genetics by knocking down gene function.

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-mRNA, direct steric blockage, and exon content modulation through splicing site binding on pre-mRNA. Several ASOs have been approved in the United States, the European Union, and elsewhere.

The dystrophin-associated protein complex, also known as the dystrophin-associated glycoprotein complex is a multiprotein complex that includes dystrophin and the dystrophin-associated proteins. It is one of the two protein complexes that make up the costamere in striated muscle cells. The other complex is the integrin-vinculin-talin complex.

In molecular biology, exon skipping is a form of RNA splicing used to cause cells to “skip” over faulty or misaligned sections (exons) of genetic code, leading to a truncated but still functional protein despite the genetic mutation.

Prosensa was a biotechnology company engaged in the discovery, development and commercialization of RNA-modulating therapeutics. The company targets genetic disorders with a large unmet medical need, with a primary focus on neuromuscular and neurodegenerative disorders such as Duchenne muscular dystrophy (DMD), myotonic dystrophy, and Huntington's disease. Prosensa was acquired by BioMarin.

Drisapersen is an experimental drug that was under development by BioMarin, after acquisition of Prosensa, for the treatment of Duchenne muscular dystrophy. The drug is a 2'-O-methyl phosphorothioate oligonucleotide that alters the splicing of the dystrophin RNA transcript, eliminating exon 51 from the mature dystrophin mRNA.

<span class="mw-page-title-main">Eteplirsen</span> Medication

Eteplirsen is a medication to treat, but not cure, some types of Duchenne muscular dystrophy (DMD), caused by a specific mutation. Eteplirsen only targets specific mutations and can be used to treat about 14% of DMD cases. Eteplirsen is a form of antisense therapy.

<span class="mw-page-title-main">Marathon Pharmaceuticals</span> Former U.S. rare disease drug company

Marathon Pharmaceuticals LLC was a privately held biopharmaceuticals company focused on drugs for people with rare diseases. The Illinois-based company developed and manufactured therapeutics and brought them to market. It employed 100 people in four global locations. In 2017, PTC Therapeutics acquired rights to Marathon Pharmaceuticals' drug Emflaza (deflazacort) for $140 million after criticism about their plan to sell the drug at a list price of $89,000 per year to sufferers despite the fact that the same drug was available in Canada and the UK for around $1,000 per year.

Catalent, Inc. is a multinational corporation headquartered in Somerset, New Jersey. It is a global provider of delivery technologies, development, drug manufacturing, biologics, gene therapies and consumer health products. It employs more than 14,000 people, including approximately 2,400 scientists and technicians. In fiscal year 2020, it generated over $3 billion in annual revenue.

<span class="mw-page-title-main">Ezutromid</span> Chemical compound

Ezutromid is an orally administered small molecule utrophin modulator involved in a Phase 2 clinical trial produced by Summit Therapeutics for the treatment of Duchenne muscular dystrophy (DMD). DMD is a fatal x-linked recessive disease affecting approximately 1 in 5000 males and is a designated orphan disease by the FDA and European Medicines Agency. Approximately 1/3 of the children obtain DMD as a result of spontaneous mutation in the dystrophin gene and have no family history of the disease. Dystrophin is a vital component of mature muscle function, and therefore DMD patients have multifarious forms of defunct or deficient dystrophin proteins that all manifest symptomatically as muscle necrosis and eventually organ failure. Ezutromid is theorized to maintain utrophin, a protein functionally and structurally similar to dystrophin that precedes and is replaced by dystrophin during development. Utrophin and dystrophin are reciprocally expressed, and are found in different locations in a mature muscle cell. However, in dystrophin-deficient patients, utrophin was found to be upregulated and is theorized to replace dystrophin in order to maintain muscle fibers. Ezutromid is projected to have the potential to treat all patients suffering with DMD as it maintains the production of utrophin to counteract the lack of dystrophin to retard muscle degeneration. Both the FDA and European Medicines Agency has given ezutromid an orphan drug designation. The FDA Office of Orphan Products and Development offers an Orphan Drug Designation program (ODD) that allows drugs aimed to treat diseases that affect less than 200,000 people in the U.S. monetary incentives such as a period of market exclusivity, tax incentives, and expedited approval processes.

<span class="mw-page-title-main">Golodirsen</span> Medication for Duchenne muscular dystrophy

Golodirsen, sold under the brand name Vyondys 53, is a medication used for the treatment of Duchenne muscular dystrophy. It is an antisense oligonucleotide medication of phosphorodiamidate morpholino oligomer (PMO) chemistry.

<span class="mw-page-title-main">Viltolarsen</span> Pharmaceutical drug

Viltolarsen, sold under the brand name Viltepso, is a medication used for the treatment of Duchenne muscular dystrophy (DMD). Viltolarsen is a Morpholino antisense oligonucleotide.

<span class="mw-page-title-main">Cure Rare Disease</span>

Cure Rare Disease is a non-profit biotechnology company based in Boston, Massachusetts that is working to create novel therapeutics using gene therapy, gene editing and antisense oligonucleotides to treat people impacted by rare and ultra-rare genetic neuromuscular conditions.

Toshifumi (Toshi) Yokota is a biomedical scientist and professor of medical genetics at the University of Alberta, also holding the titles of the Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair and the Henri M. Toupin Chair in Neurological Science. Known for pioneering research in antisense therapy for muscular dystrophy that led to the development of an FDA-approved drug viltolarsen, research interests encompass precision medicine for muscular dystrophy and genetic diseases. Publications exceed 100 refereed papers and patents, with contributions as co-editor to three books in the Methods in Molecular Biology series from Humana Press, Springer-Nature, Roles include fellow of the Canadian Academy of Health Sciences, a member of the editorial boards for numerous journals, a member of the Medical and Scientific Advisory Committee of Muscular Dystrophy Canada, chief scientific officer of OligomicsTx, and a co-founder of the Canadian Neuromuscular Network (CAN-NMD).

<span class="mw-page-title-main">Ultragenyx</span> American biopharmaceutical company

Ultragenyx Pharmaceutical Inc. is an American biopharmaceutical company involved in the research and development of novel products for treatment of rare and ultra-rare genetic diseases for which there are typically no approved treatments and high unmet medical need. The company works with multiple drug modalities including biologics, small molecule, gene therapies, and ASO and mRNAs in the disease categories of bone, endocrine, metabolic, muscle and CNS diseases.

<span class="mw-page-title-main">Casimersen</span> Medication

Casimersen, sold under the brand name Amondys 45, is an antisense oligonucleotide medication used for the treatment of Duchenne muscular dystrophy (DMD) in people who have a confirmed mutation of the dystrophin gene that is amenable to exon 45 skipping. It is an antisense oligonucleotide of phosphorodiamidate morpholino oligomer (PMO). Duchenne muscular dystrophy is a rare disease that primarily affects boys. It is caused by low levels of a muscle protein called dystrophin. The lack of dystrophin causes progressive muscle weakness and premature death.

Delandistrogene moxeparvovec, sold under the brand name Elevidys, is a recombinant gene therapy used for the treatment of Duchenne muscular dystrophy. It is designed to deliver into the body a gene that leads to production of Elevidys micro-dystrophin that contains selected domains of the dystrophin protein present in normal muscle cells. It is an adeno-associated virus vector-based gene therapy that is given by intravenous infusion.

Stephen Donald Wilton, also known as Steve Wilton, is an Australian molecular biologist and academic, serving as the Foundation Professor of Molecular Therapy at Murdoch University and adjunct professor at the University of Western Australia (UWA). He also fulfills dual roles as a Director at the Perron Institute for Neurological and Translational Science and deputy director at Murdoch's Centre for Molecular Medicine and Innovative Therapeutics (CMMIT).

References

  1. ↑ "FORM 10-K". UNITED STATES SECURITIES AND EXCHANGE COMMISSION. Retrieved 2024-10-28.
  2. ↑ Summerton, J (2005). "Morpholino Antisense Oligos: Applications in Biopharmaceutical Research". Innovations in Pharmaceutical Technology. No. Sept. Retrieved 29 Oct 2012. | archiveurl = http://www.gene-tools.com/sites/default/files/Summerton2005_IPT.pdf
  3. ↑ "AVI BioPharma changes name, splits stock". Portland Business Journal. July 12, 2012. Retrieved 17 July 2012.
  4. ↑ Summerton, James E. (2017). "Invention and Early History of Morpholinos". In Moulton, Hong; Moulton, Jon (eds.). Morpholino Oligomers. Methods in Molecular Biology. Vol. 1565. New York, NY USA: Humana Press. ISBN   978-1-4939-6815-2.
  5. 1 2 Moody, Robin J. (November 5, 2003). "AVI BioPharma's losses shrinking". Portland Business Journal. Retrieved 2009-10-24.
  6. ↑ Moody, Robin J. (June 12, 2003). "AVI BioPharma stock reaches new 52-week high". Portland Business Journal. Retrieved 2009-10-24.
  7. 1 2 3 4 DiMesio, Robbie (July 30, 2009). "AVI BioPharma moving HQ out of Oregon". The Oregonian . Retrieved 2009-10-24.
  8. ↑ "AVI BioPharma loses $19.7M in Q2". Portland Business Journal. August 10, 2009. Retrieved 2009-10-24.
  9. 1 2 "AVI BioPharma gets $11.5M military contract". Portland Business Journal. October 5, 2009. Retrieved 2009-10-24.
  10. ↑ Timmerman, Luke. Sarepta Moves From Seattle to Boston for the Talent. 7 September 2012.
  11. ↑ Siefert, Kate (2023-05-09). "'It's transformational work,' Sarepta working on groundbreaking gene therapies in Columbus". WSYX. Retrieved 2023-10-05.
  12. ↑ Murphy, Mike (2017-06-28). "Sarepta Therapeutics names new CEO". MarketWatch. Retrieved 2024-10-28.
  13. ↑ Renauer, Cory (2019-03-26). "Is Sarepta Therapeutics a Good Gene Therapy Stock to Buy Now? -". The Motley Fool. Retrieved 2019-05-21.
  14. ↑ "Our Pipeline, Building an industry-leading genetic medicine pipeline". Sarepta Therapeutics.
  15. ↑ "Sarepta and Catalent Expand Strategic Manufacturing Partnership With Commercial Supply Agreement for Duchenne Muscular Dystrophy Gene Therapy Candidate". www.businesswire.com. 2023-01-05. Retrieved 2023-01-24.
  16. ↑ Tarun, Shafiul Islam. "Sarepta marches forward with its potential DMD gene therapy and an expanded Catalent manufacturing deal". Endpoints News (in English, Bengali, and Hindi). Retrieved 2023-01-24.
  17. ↑ Keenan, Joseph (2023-01-05). "Catalent inks deal to manufacture Sarepta's DMD gene therapy". Fierce Pharma. Retrieved 2023-01-24.
  18. ↑ Tirrell, Meg (2023-06-22). "FDA approves $3.2 million gene therapy for rare muscular dystrophy in kids ages 4 and 5". CNN. Retrieved 2024-10-28.
  19. ↑ "A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Dose of SRP-5051 in Patients With Duchenne Muscular Dystrophy (DMD) - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  20. ↑ Commissioner, Office of the (6 March 2019). "FDA grants accelerated approval to first drug for Duchenne muscular dystrophy". FDA.
  21. ↑ Therapeutics, Sarepta. "Sarepta Therapeutics Announces FDA Approval of AMONDYS 45™ (casimersen) Injection for the Treatment of Duchenne Muscular Dystrophy (DMD) in Patients Amenable to Skipping Exon 45". Sarepta Therapeutics.
  22. ↑ Sarepta's Marburg Drug Shows High Survival Rates After Intramuscular Delivery in Non-Human Primates. Marketwire, 4 March 2013.
  23. ↑ U.S. Food and Drug Administration, Silver Springs, Maryland. News Release: FDA grants accelerated approval to first targeted treatment for rare Duchenne muscular dystrophy mutation, December 12, 2019. Archived December 13, 2019, at the Wayback Machine
  24. ↑ "A Biotech Growth Stock to Consider For Your Portfolio - Sarepta Therapeutics (NASDAQ: SRPT)". www.biocompounding.com. 2 October 2022.
  25. ↑ "Roche erwirbt Gentherapie von Sarepta Therapeutics | CHEManager". www.chemanager-online.com (in German). Retrieved 2024-09-20.
  26. ↑ Leo, Leroy; Samal, Aditya (22 June 2023). "US FDA approves Sarepta's gene therapy for rare muscular dystrophy in some kids". Reuters. Archived from the original on 29 June 2023. Retrieved 26 July 2023.
  27. ↑ Stein, Rob (22 June 2023). "Muscular dystrophy patients get first gene therapy". NPR. Archived from the original on 25 July 2023. Retrieved 26 July 2023.
  28. 1 2 Mendoza, Melissa; Marks, Peter. "June 22, 2023 Approval Letter - ELEVIDYS". FDA. Archived from the original on 26 June 2023. Retrieved 26 July 2023.
  29. ↑ "The Accelerated Approval Pathway and Rare Diseases" (PDF). EveryLife Foundation for Rare Diseases. Archived (PDF) from the original on 25 February 2022. Retrieved 26 July 2023.
  30. ↑ Howard, Jacqueline (2024-06-20). "FDA expands approval of first gene therapy for rare form of muscular dystrophy". CNN. Retrieved 2024-10-28.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.