Opicinumab

Opicinumab (BIIB033) is a fully human monoclonal antibody designed for the treatment of multiple sclerosis, acute optic neuritis (AON), and other associated demyelinating diseases.^[1] A biologic drug, it is designed to function as a LINGO-1 protein antagonist, known as “Anti-Lingo-1”.^[2] Phase II clinical trials are ongoing, 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-respone relationships. Further studies are 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] 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][6] 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.^[7] As for RENEW’s secondary endpoint, there was no statistically significant change in either visual function or retinal thickness.^[1]

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][8] 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.^[9] 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.^[10] Moreover, Biogen has a fourth 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.^[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.

Commercialization

Opicinumab is manufactured by Biogen Idec, Inc., also known just as Biogen, Inc. Because opicinumab is still in Phase II trials, there is no predicted market price for the drug as of September 2016.^[9] Currently, H.C. Wainwright & Co. rates Biogen stock as investment-worthy, due in part to Biogen’s many other successful drugs, especially Tecfidera, and despite the SYNERGY trial’s less-than-ideal results.^[16] Founded in 1978, Biogen, Inc. is the one of the world’s oldest biotechnology research companies, with a specific emphasis on MS research and treatment.^[7] Biogen has over 7,000 employees globally.^[17] In addition to manufacturing many FDA approved drugs for the treatment of MS, they also sell drugs for the treatment of hemophilia, leukemia, non-Hodgkin’s lymphoma, and rheumatoid arthritis.^[17]

The most recent financial data from Biogen indicates worldwide revenues of almost $3.0 billion dollars for 2016 Quarter 3 alone. This is a 13% GAAP diluted EPS rise over 2015 Quarter 3 financial results.^[16] Biogen’s Tecfidera, Avonex, and Tysabri garnered the company the greatest revenues in 2015 Quarter 3, as well as in 2016 Quarters 2 and 3.^[16] Tecfidera alone was responsible for approximately 40 percent of Biogen’s revenue in 2016 Quarter 3.^[16] In all, the company saw a 2% increase in revenue in 2016 Quarter 3 over 2016 Quarter 2 and a 6% increase in revenue over 2015 Quarter 3.^[16]

References

1. 1 2 3 4 5 6 "Biogen Reports Top-Line Results from Phase 2 Study of Opicinumab (Anti-LINGO-1) in Multiple Sclerosis | Biogen Media". media.biogen.com. Retrieved 2016-11-21. 
2. 1 2 3 "Opicinumab". drugspider.com. Retrieved 2016-11-21. 
3. ↑ "BIIB033 Single Ascending Dose Study in Healthy Volunteer Subjects - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2016-11-21. 
4. ↑ "Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of BIIB033 in Healthy Japanese Participants - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2016-11-21. 
5. ↑ "Safety Study of BIIB033 in Subjects With Multiple Sclerosis - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2016-11-21. 
6. ↑ "BIIB033 In Acute Optic Neuritis (AON) - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2016-11-21. 
7. 1 2 "Biogen Idec Reports Positive Top-Line Results from Phase 2 Anti-LINGO-1 Trial in People with Acute Optic Neuritis | Business Wire". www.businesswire.com. Retrieved 2016-11-21. 
8. ↑ "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". clinicaltrials.gov. Retrieved 2016-11-21. 
9. 1 2 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.
10. ↑ "Long-Term Assessment of Remyelinating Therapy - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2016-11-21. 
11. ↑ "Pharmacokinetics, Safety and Tolerability of Single Doses of BIIB033 (Opicinumab) Produced by 2 Manufacturing Processes - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2016-11-21. 
12. ↑ Mi, Sha (2009-04-17), Methods for Treating Pressure Induced Optic Neuropathy, Preventing Neuronal Degeneration and Promoting Neuronal Cell, Survival Via Administration of Lingo-1 Antagonists and Trkb Agonists, retrieved 2016-11-21 
13. ↑ Cadavid, Diego; Mi, Sha (2016-07-15), Lingo-1 Antagonists and Uses for Treatment of Demyelinating Disorders, retrieved 2016-11-21 
14. ↑ "IP Services". www.wipo.int. Retrieved 2016-11-21. 
15. ↑ "What Is a WO Patent?". Retrieved 2016-11-21. 
16. 1 2 3 4 5 "Biogen Reports Record Third Quarter 2016 Revenues of $3.0 Billion | Biogen Media". media.biogen.com. Retrieved 2016-11-21. 
17. 1 2 "About Biogen". www.biogen.com. Retrieved 2016-11-21.