“Opicinumab”的意思、由来-开放百科全书

Some Phase II clinical trials have been carried out, but preliminary results released by the drug's developer, Biogen Idec Inc., indicate that primary study endpoints were not met and that opicinumab exhibits unexpected dose-response relationships. Further studies were planned by the company, as opicinumab still was deemed to show potential for clinical efficacy in the treatment of MS.^[1]

Mechanism of action

Opicinumab is designed to prevent the advancement of demyelination associated with neurodegenerative disorders, specifically MS. It is believed to function by allowing young cells, which would normally be prevented from maturing by the LINGO-1 protein, to mature into functional oligodendrocytes. Oligodendrocytes support nerve axons and serve to maintain the myelin sheath that allows for the effective conduction of axon potentials.^[2] LINGO-1 is only found in the Central Nervous System (CNS) and is thought to be at least a partial causative agent of MS, an autoimmune disorder. It is thought that by allowing oligodendrocytes to mature, further disability advancement caused by MS can be prevented, with reversal of demyelination associated with MS potentially achievable.^[1]^[2]

Clinical trials

Phase I and Phase II clinical trials are currently ongoing for opicinumab. Completed Phase I trials assessed safety and efficacy in healthy people and in MS patients, as well as investigated pharmacokinetic parameters of the drug.^[3]^[4]^[5]

Biogen has an ongoing Phase 1 trial that is investigating the safety of ocipinumab produced via two different manufacturing processes in healthy individuals. That trial is set to conclude November 2016.^[6]

Acute optic neuritis

The completed Phase II trial, dubbed RENEW by Biogen, studied the potential clinical efficacy of opicinumab in treating AON, more specifically in repairing damage done to the optic nerve.^[1]^[7] The study successfully reached its primary endpoint and showed a 34 percent partial recovery of optic nerve latency, a measure of the time of conduction from the retina to the visual cortex.^[8] On RENEW's secondary endpoint, there was no statistically significant change in either visual function or retinal thickness.^[1]

Multiple sclerosis

The second completed Phase II clinical trial for opicinumab, called SYNERGY by Biogen, concluded in March 2016 but failed to reach its primary endpoint, which was an integrated measure of several MS progression and disability markers: ambulation, extremity functionality, cognition, and other typical indicators of MS.^[1]^[9] Results from the study also showed highly unanticipated dose-response relationships in the MS patient population that will likely require further clinical trials to investigate satisfactorily.^[10] Despite the undesired study results, Biogen still has faith in ability of opicinumab to become a viable treatment option for MS and demyelination disease patients, as the company currently has active enrollment for a third clinical trial, which began in March 2016 and is set to conclude in February 2017. This ongoing trial is investigating the efficacy of long-term treatment with opicinumab in target populations.^[11]

Intellectual property

Biogen, Inc. filed its first patent application with WIPO (World Intellectual Property Organization) in 2008, wherein the potential to target LINGO-1 in patients suffering from MS was described.^[12]

In January 2016, Biogen filed a second patent application with WIPO that specifically described and protected BIIB003 (opicinumab).^[13] By filing with WIPO, the overseeing organization for the Patent Cooperation Treaty (PCT), Biogen gains an extra year of intellectual property (IP) exclusivity after submitting its international patent application with WIPO to apply for patents in all desired member states of the PCT.^[14]^[15] Therefore, Biogen has until January 2017 to file patent applications for opicinumab in multiple countries of its choosing, after which its IP will no longer be protected by the PCT.

References

1. ^¹²³⁴⁵{{Cite web|url=http://media.biogen.com/press-release/investor-relations/biogen-reports-top-line-results-phase-2-study-opicinumab-anti-lingo|title=Biogen Reports Top-Line Results from Phase 2 Study of Opicinumab (Anti-LINGO-1) in Multiple Sclerosis {{!}} Biogen Media|website=media.biogen.com|access-date=2016-11-21}}
2. ^¹²{{Cite web|url=http://drugspider.com/drug/opicinumab|title=Opicinumab|website=drugspider.com|access-date=2016-11-21}}
3. ^{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT01052506?term=biib033&rank=1&submit_fld_opt|title=BIIB033 Single Ascending Dose Study in Healthy Volunteer Subjects - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov|access-date=2016-11-21}}
4. ^{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT02641041?term=biib033&rank=5|title=Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of BIIB033 in Healthy Japanese Participants - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov|access-date=2016-11-21}}
5. ^{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT01244139?term=biib033&rank=4&submit_fld_opt|title=Safety Study of BIIB033 in Subjects With Multiple Sclerosis - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov|access-date=2016-11-21}}
6. ^{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT02833142?term=biib033&rank=2&submit_fld_opt|title=Pharmacokinetics, Safety and Tolerability of Single Doses of BIIB033 (Opicinumab) Produced by 2 Manufacturing Processes - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov|access-date=2016-11-21}}
7. ^{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT01721161?term=biib033&rank=3|title=BIIB033 In Acute Optic Neuritis (AON) - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov|access-date=2016-11-21}}
8. ^{{Cite web|url=http://www.businesswire.com/news/home/20150108005446/en/Biogen-Idec-Reports-Positive-Top-Line-Results-Phase|title=Biogen Idec Reports Positive Top-Line Results from Phase 2 Anti-LINGO-1 Trial in People with Acute Optic Neuritis {{!}} Business Wire|website=www.businesswire.com|access-date=2016-11-21}}
9. ^{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT01864148?term=biib033&rank=6|title=Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Participants With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov|access-date=2016-11-21}}
10. ^Fein, Andrew S., Rachel F Lane, and Emile Yu (September 19, 2016). “First Take: Our Takeaways from SYNEGY”. H.C. Wainwright & Co. H.C. Wainwright & Co. Retrieved November 20, 2016.
11. ^{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT02657915?term=biib033&rank=7|title=Long-Term Assessment of Remyelinating Therapy - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov|access-date=2016-11-21}}
12. ^{{Citation|last=Mi|first=Sha|title=Methods for Treating Pressure Induced Optic Neuropathy, Preventing Neuronal Degeneration and Promoting Neuronal Cell, Survival Via Administration of Lingo-1 Antagonists and Trkb Agonists|date=2009-04-17|url=https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2009048605&redirectedID=true|accessdate=2016-11-21}}
13. ^{{Citation|last=Cadavid|first=Diego|title=Lingo-1 Antagonists and Uses for Treatment of Demyelinating Disorders|date=2016-07-15|url=https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2016112270&redirectedID=true|last2=Mi|first2=Sha|accessdate=2016-11-21}}
14. ^{{Cite web|url=http://www.wipo.int/services/en/|title=IP Services|website=www.wipo.int|access-date=2016-11-21}}
15. ^{{Cite news|url=http://smallbusiness.chron.com/wo-patent-64013.html|title=What Is a WO Patent?|access-date=2016-11-21}}