Terbinafine topical - Celtic Pharma
`
`Publication info: Adis R&D Insight . (May 11, 2015).
`ProQuest document link
`
`Full text: DRUG PROFILE - Terbinafine topical - Celtic Pharma
`As of May 2015, no recent reports of development for topical terbinafine (TDT 067) have been identified for the
`treatment of onychomycosis. The product was under phase III development with Celtic Pharma in the US,
`Germany and Iceland. The product was the lead compound in a research programme originally created by IDEA
`AG. TDT 067 (IDEA 067) contains the anti-fungal drug terbinafine and utilises IDEA AG's proprietary
`Transfersome ®drug delivery technology. Transfersomes ®are bio-compatible, highly deformable, self-regulating,
`water-based vesicles, which are used to transport established, low molecular weight drugs selectively into the
`skin and in the immediately adjacent underlying tissues.
`COMPANY AGREEMENTS
`In February 2006, Celtic Pharma acquired worldwide rights to topical terbinafine, following the acquisition of an
`exclusive global license to IDEA's Transfersome ®drug delivery technology (Reference: 809061326).
`KEY DEVELOPMENT MILESTONES
`As of May 2015, no recent reports of development for topical terbinafine have been identified for the treatment
`of onychomycosis.
`
`Celtic Pharma initiated a randomised, double-blind, vehicle- and placebo-controlled phase III trial in April 2010,
`to assess the efficacy and safety of topical terbinafine 1.5% in patients with mild to moderate distal subungual
`onychomycosis of the toenails (NCT01145807; EudraCT 2010-018793-21; CL-067-III-01). Treatment was
`applied twice-daily for 48 weeks, and the primary endpoint was cure rate at 52 weeks. The trial enrolled 738
`patients in the US, Germany and Iceland, and was completed in January 2012. Celtic Pharma appointed PPD
`Inc., a global contract research organisation, to conduct the study (Reference: 809111963) (Reference:
`700244950).
`
`Celtic Pharma initiated a randomised, crossover phase II trial in December 2009, to establish a clinical bridge
`between topical terbinafine and terbinafine oral tablets (Lamisil ®) in patients with distal subungual
`onychomycosis of the toenails (NCT01790165). The aim of the trial was to confirm that treatment with topical
`terbinafine is associated with significantly lower plasma levels of terbinafine, than the oral formulation. The trial
`enrolled 27 patients in the US, and was completed in June 2012 (Reference: 700244953).
`
`In June 2008, Celtic Pharma enrolled the first patient into a phase II trial, designed to assess the efficacy and
`safety of topical terbinafine (Reference: 809090275). The trial was completed and results were reported in
`March 2009 (Reference: 809110799).
`
`At the BioSquare-2005 meeting, IDEA announced that topical terbinafine was undergoing further research for
`the treatment onychomycosis (Reference: 801009169).
`
`Data from two in vitro studies of TDT 067 were reported in February 2011 (Reference: 809121232).
`
`
`
`Adverse Event
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2184 - 1/7
`
`

`
`TDT 067 was well tolerated in a phase II trial in patients with onychomycosis. Systemic drug exposure was
`negligible; no patient had >2 ng/mL of terbinafine at steady state and majority of patients had levels below 1
`ng/mL. No serious local side effects were reported (Reference: 809110799).
`
`
`
`Pharmacokinetics
`In a pharmacokinetic study, maximally used TDT 067 achieved two orders of magnitude lower plasma
`concentrations of terbinafine compared with oral terbinafine. In contrast, terbinafine levels in affected nails were
`three orders of magnitude higher compared with oral terbinafine (Reference: 809111963).
`
`
`
`Pharmacodynamics
`Mycoses
`TDT 067 was shown in vitro to have potent inhibitory and fungicidal activity against dermatophyte strains. Data
`also demonstrated that TDT 067 has more potent fungicidal activity than conventional terbinafine preparations.
`In another in vitro study, the terbinafine formulated in transfersomes in TDT 067 was shown to potentiate the
`action of terbinafine by enabling it to penetrate more effectively to its site of action inside the fungus, disrupting
`the intracellular matrix and eventually killing dermatophyte hyphae (Reference: 809121232).
`
`
`
`Therapeutic Trials
`Mycoses
`Treatment with TDT 067 resulted in 90% negative mycological cure rate at 14 weeks in a phase II trial in
`patients with onychomycosis. At 48 weeks, the mycological cure rate was 38%. In the study, patients were
`treated with TDT 067 for 12 weeks and the primary endpoint of mycological cure was measured at 14 weeks
`and 48 weeks (Reference: 809110799).
`
`
`
`Pharmacodynamics
`More potent in vitro than conventional terbinafine preparations
`
`
`
`References
`801009169. Company overview. IDEA AG. BioSquare 2005. : [1 page], 13 Apr 2005. English. Germany
`809061326. Celtic Pharma Licenses Targeted Drug Delivery Technology and Dermatological Product Portfolio
`From Idea Ag. Celtic Pharmaceutical Holdings LP, IDEA AG. Media Release. : 23 Feb 2006. Available from:
`URL: http://www.idea-ag.de. English. Bermuda
`809090275. Celtic Pharma Announces Initiation of Phase II Clinical Trial for Tdt-067, a Treatment for
`Onychomycosis. Celtic Pharmaceutical Holdings L.P. Media Release. : 15 Oct 2007. Available from: URL:
`http://www.celticpharma.com. English. England
`809110799. Celtic Pharma Announces Successful Outcome of Phase II Trial for Topical Treatment of
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2184 - 2/7
`
`

`
`Onychomycosis. Celtic Pharma. Media Release. : 26 Mar 2010. Available from: URL:
`http://www.celticpharma.com. English. USA
`809111963. Celtic Pharma Announces Initiation of Phase III Trial of TDT 067 for the Treatment of
`Onychomycosis. Celtic Pharmaceutical Holdings L.P. Media Release. : 30 Apr 2010. Available from: URL:
`http://www.celticpharma.com. English. England
`809121232. Celtic Pharma Announces Presentation of Preclinical Data at the 69th Annual Meeting of the AAD
`in New Orleans. Celtic Pharma. Media Release. : 8 Feb 2011. Available from: URL:
`http://www.celticpharma.com. English. USA
`700244950. A Randomized, Double-blind, Vehicle- and Placebo-Controlled, Multicenter Trial in Patients With
`Mild to Moderate Distal Subungual Toenail Onychomycosis to Investigate the Efficacy, Tolerability, and Safety
`of Twice Daily Application of TDT 067 for 48 Weeks
`700244953. A Phase II Open Label Multiple-Dose Study of the Safety and Pharmacokinetics of TDT 067 Under
`Conditions of Maximal Use in Subjects With Distal Subungual Onychomycosis of the Toenails
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2184 - 3/7
`
`

`
`N
`
`CFAD V. Anacor, IPR2015-01776 ANACOR EX. 2184 - 4/7
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2184 - 4/7
`
`

`
`
`
`History of Drug Development
`
`Event
`date
`
`Update
`date
`
`Update type
`
`Significa
`nt
`
`Details
`
`200406
`15
`
`2004070
`1
`
`Phase
`Change
`
`true
`
`Preclinical trials in Onychomycosis in Germany (unspecified
`route)
`
`200407
`01
`
`2004070
`1
`
`New Profile
`
`true
`
`Profile created from data presented at the BIO 2004
`International Annual Convention (BIO-2004)
`
`200602
`23
`
`2006031
`6
`
`Licensing
`Status
`
`200710
`15
`
`2008062
`0
`
`Phase
`Change
`
`true
`
`IDEA 067 has been licensed to Celtic Pharma worldwide
`
`false
`
`Phase-II clinical trials in Onychomycosis in USA (Topical)
`
`200903
`26
`
`2010032
`5
`
`Scientific
`Update
`
`false
`
`Efficacy and safety data from a phase II trial in
`Onychomycosis released by Celtic Pharma (9110799)
`
`200903
`26
`
`2010082
`7
`
`200912
`31
`
`2013022
`6
`
`Trial Update
`
`false
`
`Celtic Pharma completes a phase-II trial in Onychomycosis in
`USA (Topical)
`
`Trial Update
`
`true
`
`Celtic Pharma initiates enrolment in a phase II trial for
`Onychomycosis in USA (NCT01790165)
`
`201004
`30
`
`2010050
`3
`
`Phase
`Change
`
`true
`
`Phase-III clinical trials in Onychomycosis in USA (Topical)
`
`201005
`03
`
`2010050
`3
`
`Scientific
`Update
`
`true
`
`Pharmacokinetic data from a phase II trial in Onychomycosis
`released by Celtic Pharma (9111963)
`
`201005
`05
`
`2013022
`6
`
`Phase
`Change
`
`201005
`05
`
`2013022
`6
`
`Phase
`Change
`
`201102
`08
`
`2011020
`9
`
`Scientific
`Update
`
`true
`
`Phase-III clinical trials in Onychomycosis in Iceland (Topical)
`
`true
`
`true
`
`Phase-III clinical trials in Onychomycosis in Germany
`(Topical)
`
`Pharmacodynamics data from in vitro studies in
`Onychomycosis presented at the 69th Annual Meeting of the
`American Academy of Dermatology (AAD-2011) (9121232)
`
`201201
`
`2013022
`
`Celtic Pharma completes a phase III trial in Onychomycosis
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2184 - 5/7
`
`

`
`13
`
`6
`
`Trial Update
`
`true
`
`in USA, Germany &Iceland (NCT01145807)
`
`201206
`30
`
`2013022
`6
`
`Trial Update
`
`true
`
`Celtic Pharma completes a phase II trial for Onychomycosis
`in USA (NCT01790165)
`
`201505
`11
`
`2015051
`1
`
`Phase
`Change
`
`true
`
`No recent reports on development identified- Phase-III for
`Onychomycosis in USA, Iceland and Germany (Topical)
`
`
`
`Development Phases
`
`Phase
`
`Count
`ry
`
`Indication
`
`Route of
`Administration
`
`Formulati
`on
`
`On Fast
`Track
`
`Qualifiers and
`Comments
`
`No development
`reported(III)
`
`Germ
`any
`
`Onychomy
`cosis
`
`Topical
`
`No development
`reported(III)
`
`Icelan
`d
`
`Onychomy
`cosis
`
`Topical
`
`Spray
`
`false
`
`Spray
`
`false
`
`No development
`reported(III)
`
`Topical
`
`Spray
`
`false
`
`USA
`
`Onychomy
`cosis
`
`
`Subject: Naphthalenes;Small-molecules
`
`Substance: Substance Substance: 1-Naphthalenemethanamine, N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-,
`(E) -; CAS: 91161-71-6;
`
`Drug synonym: IDEA-067, TDT-067, Terbinafine cutaneous suspension
`
`Molecular formula: C21H25N
`
`Generic name: Terbinafine topical - Celtic Pharma
`
`Origin of substance: Fixed combination: No
`
`Route of administration: Topical
`
`Mechanism of action: Squalene-monooxygenase-inhibitors
`
`Therapeutic class: D1A1: Topical dermatological antifungalsD01A-E15: Terbinafine
`
`Indication: Onychomycosis
`
`Drug status: Inactive
`
`Company information: Name: Celtic Pharma, Private, Not-Large-Pharma; Unknown; Role: Licensee; Region:
`World;
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2184 - 6/7
`
`

`
`Name: IDEA, Private, Not-Large-Pharma; Biopharmaceutical; Role: Originator; Region: Germany;
`Name: TDT, Not-Large-Pharma; Unknown; Role: Licensee; Region: World;
`
`Highest phase: No development reported(III)
`
`Language: English
`
`Document type: Report
`
`Publication title: Adis R&D Insight
`
`Publication type: Reports
`
`Publication date: May 11, 2015
`
`Date created: 2004-07-02
`
`Date revised: 2015-05-11
`
`Source attribution: Adis R&D Insight, © Publisher specific
`
`Accession number: 20969
`
`Document URL: http://dialog.proquest.com/professional/docview/1030580524?accountid=150768
`
`First available: 2012-08-02
`
`Updates: 2013-02-282014-01-212015-05-14
`
`Database: Adis R&D Insight; 1995 to date (1995 - current)
`
`_______________________________________________________________
` Contact ProQuest
`Copyright (cid:211) 2016 ProQuest LLC. All rights reserved. - Terms and Conditions
`
`
`CFAD v. Anacor, IPR2015-01776 ANACOR EX. 2184 - 7/7