ADIS R&D PROFILE
`
`BG 12
`
`Drugs R D 2005; 6 (4): 229-230
`1 174-5886/05/0004-0229/$34.95/0
`
`© 2005 Adis Data Information BV. All rights resewed.
`
`BG 00012, BG 12/Oral Fumarate, FAG-201,
`Second-Generation Fumarate Derivative — Fumapharml
`Biogen Idec
`
`Abstract
`
`Fumapharm AG has developed a second-generation f11rnarate (fumaric acid)
`derivative, BG 12 [BG 00012, FAG-201, BG 12/Oral Fumarate], for the oral
`
`treatment of psoriasis. Biogen Idec is currently evaluating the product in clinical
`trials as an oral treatment for multiple sclerosis (phase II) and psoriasis (phase III)
`trials.
`
`BG 12 has an immunomodulatory mechanism of action. It seems that this
`product has been developed to reduce the adverse effects associated with a first-
`generation product containing fumaric acid esters (mixed dimethylfumarate and
`monoethylfumarate salts), Fumaderm®. Fumaderm® was approved in Germany in
`August 1994 and is currently the leading oral systemic therapy for moderate—to—
`severe psoriasis in Germany. One of the problems associated with Fumaderm®
`capsules has been its gastrointestinal adverse effects (including diarrhoea and
`nausea).
`In September 2003, Biogen (now Biogen Idec) licensed exclusive worldwide
`rights (excluding Germany) from Fumapharm to develop and market BG 12.
`Biogen plans to collaborate with Fumapharm to accelerate phase HI development
`for psoriasis and the registration programme worldwide. Financial terms of the
`agreement were not disclosed. Development plans for BG 12 include other
`autoimmune and inflammatory disorders, such as multiple sclerosis.“~2]
`In November 2003, Biogen and IDEC Pharmaceuticals merged to form Biogen
`Idec. Fumapharm completed phase II trials of this second-generation fumarate
`derivative for psoriasis prior to licensing of the product to Biogen, also with
`positive results.“]
`
`1. Profile
`
`1 .1 Adverse Events
`
`severe psoriasis were flushing and diarrhoea. In
`addition, one patient was hospitalised with pneumo-
`
`nia and another was hospitalised with kidney
`stones.[3]
`
`Clinical studies: The most common adverse
`
`1.2 Therapeutic Triols
`
`events reported in a phase II trial of BG 12 were
`flushing, elevations in liver function tests and com-
`mon colds, which were generally transient and mild-
`to—moderate in severity.[”
`The most common adverse events reported in a
`phase III study of 175 patients with moderate—to-
`
`1.2.1 Skin Disorders
`
`In a phase H dose-ranging trial, patients with
`severe psoriasis who received BG 12 experienced
`greater improvement in their psoriasis than patients
`receiving placebo. Patients
`(n = 144) were
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`Coalition Exhibit 1021A
`
`Coalition V. Biogen
`IPR2015—01136
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`Page 1 of 2
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`230
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`Table I. Features and properties
`WHO ATC code
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`EphMFlA ATC code
`
`Originator
`Licensee companies
`Highest development phase
`
`Properties
`Mechanism of action
`Route
`Adverse events
`
`Table II. Drug development history
`Jul 2003
`
`Sep 2003
`
`Oct 2003
`Nov 2003
`Nov 2004
`
`Apr 2005
`
`D05B-X51 (Fumaric acid derivatives, combinations)
`N07X-X (Other nervous system drugs)
`N7X (All other CNS drugs)
`D5B (Systemic Antipsoriasis Products)
`Fumapharm AG: Switzerland
`Biogen Idec: World
`Phase II (Europe)
`
`lmmunomodulators
`PO
`
`Flare: Common cold, Diarrhoea, Elevated liver enzymes, Flushing
`
`Phase-I in Multiple sclerosis in Europe (PO)
`This second-generation fumarate derivative has been licensed to
`Biogen worldwide (excluding Germany) for Psoriasis
`Phase-Ill in Psoriasis in Europe (PO)
`IDEC Pharmaceuticals has merged with Biogen to form Biogen ldec
`Phase-ll in Multiple sclerosis in Europe (PO)
`Phase-Ill in Psoriasis in Germany (PO)
`
`randomised to either placebo or BG 12 (120, 360 or
`
`tions from baseline in PASI were 68% and 10% in
`
`720 mg/day) for 12 weeks. At 12 weeks, 42% of
`
`the BG 12 and placebo groups, respectively.”-5]
`
`patients who received BG 12 720 mg/day achieved
`at least a 75% improvement in their Psoriasis Area
`and Severity Index (PASI 75), compared with 11%
`
`of patients who received placebo. The mean per-
`
`centage reductions in PASI from baseline were
`71%, 52%, 31% and 6% for the 720, 360, 120 mg/
`day and placebo groups, respectively. It was also
`
`noted that some patients began improving as early as
`2 weeks after BG 12 was administered.“~4]
`
`Favourable efficacy and tolerability through to
`week 16 have been reported in a phase III study in
`Europe. In this multicentre, double-blind study con-
`ducted by Fumapharm, 175 patients with moderate-
`to—severe chronic plaque psoriasis were randomised
`to receive BG 12 240mg three times daily (11 = 105)
`or placebo (11 = 70) for 16 weeks. At 16 weeks, the
`median PASI was 5.8 in the BG 12 group and 14.2
`in the placebo group. The median percentage reduc-
`
`References
`1. Biogen Idec, Fumapharm AG. Patients Show Improvement in
`Phase II Psoriasis Study of Novel Oral Immunomodulator.
`Media Release: 29 Apr 2004. Available from URL: http://
`www.biogen.com
`2. Biogen Inc. Biogen Licenses Oral Psoriasis Therapy From
`Fumapharm AG. Media Release: 1 Oct 2003. Available from
`URL: http://www.biogen.com
`3. Biogen Idec. BG-12 Psoriasis Study Meets Primary Endpoint;
`Oral Compound Also Being Studied for MS in Phase II Trial.
`Media Release: 7 Apr 2005. Available from URL: http://
`www.biogenidec.com
`4. Langner A, Spellman MC. Results of a phase 2 dose-ranging
`and safety extension study of a novel oral fumarate, BG-12, in
`patients with severe psoriasis. Journal of the American Acade-
`my of Dermatology 52 (Abstr. Suppl.): 193 (plus poster) abstr.
`P2787, No. 3, Mar 2005
`5. Mrowietz U, Spellman MC. Efficacy and safety of a novel
`formulation of an oral fumarate, BG-12, in patients with mod-
`erate to severe plaque psoriasis: results of a phase I[[ study.
`Journal of the American Academy of Dermatology 52 (Abstr.
`Suppl.): 182 (plus poster) abstr. P2743, No. 3, Mar 2005
`
`© 2005 Adis Data Information BV. All rights resewed.
`
`Drugs R D 2005; 6 (4)
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