gilmore o‘neill'cainbridgeflbiogen;nsf;gi1more.oneillebiogenidec.com;smtp
`Tue Jar 31 2006 17:05:01 EST
`
`lkapposQiuhbsch;
`raehel lebouteiller/londonflbiogen@biogenidecz
`C1900 ENS abstracts
`
`
`
`From:
`Sent:
`
`T0:
`BCC:
`Subject:
`
`Dear Ludwig,
`
`it was good to see you and to meet Sofia at the National Faculty Meeting. 1 am now inspired to start bringing my
`children with me to meetings when they are older.
`
`Thank you for your help and advise with the presentation of the "top line" C1900 data.
`
`[have attached two draft abstracts on the 24 week C1900 data. Would you be able to review them and make whatever
`changes or suggested changes that you like. I have left out the specific numbers and data so that they be freshly
`presented at ENS.
`
`If you send it back to me, 1 could disseminate it to the other members of the SAC. I will also ask Rachel to pull out the
`Steering Commitee charter section on authorship that was agreed at the inaugural meeting. Twill also ask her to find the
`names of the highest recruting investigators, per the charter section. Would that be okay with you?
`
`Best regards
`
`Gilmore
`
`PS Hope that your drive along Alligator alley was interesting.
`
`E
`ENS 0000012 safety in ME: 300 000.: ENS 0000012 3005.20 in MS $0231.00”:
`
`
`
`Gilmore N. O'Neill. M.B., M.R.C.P.I., M. Med. Sci.
`Director
`
`Clinical Development—Neurology
`biogenidec
`14, Cambridge Center, Bio 4
`Cambridge, MA 02142
`Tel: 617-6792000
`Fax: 617-679-3518
`
`Page 1 of 6
`
`Biogen Exhibit 2093
`
`Mylan v. Biogen
`IPR 2018-01403
`
`Biogen Exhibit 2093
`Mylan v. Biogen
`IPR 2018-01403
`
`Page 1 of 6
`
`

`

`Efficacy of a Novel Oral Single-Agent Fumarate, BG00012, in Patients With
`Relapsing-Remitting Multiple Sclerosis: Results of a Phase 2 Study
`
`<<Please enter authors and afliliations>>
`
`<<Character limit: 2500; Character count: 2145>>
`
`Objective: To determine the efficacy of three dose levels of BG00012, a novel single-
`agent oral fiimarate, on brain lesion activity as measured by magnetic resonance imaging
`(MRI) in patients with relapsing-remitting multiple sclerosis (RRMS).
`Methods: This was a randomized, double-blind, placebo-controlled clinical trial of
`BG00012 in patients with RRMS. Men and women 18 to 55 years of age were eligible
`for the study if they had a diagnosis of RRMS and an Expanded Disability Status Scale
`
`(EDSS) score between 0.0 and 5.0. In addition, patients must have had either 21 relapse
`within 12 months prior to randomization or gadolinium-enhancing (Gd+) lesions on
`cranial MRI at screening. Patients received BG00012 120 mg by mouth (PO) once daily
`(120 mg/day), 120 mg PO three times daily (360 mg/day), 240 mg PO three times daily
`(720 mg/day), or placebo for 24 weeks. The treatment period was followed by a 24—week
`dose-blinded safety-extension period during which all patients received BGOOOl2. The
`primary end point was the total number of Gd+ lesions over four MRI scans at weeks 12,
`l6, 20, and 24 (calculated as the sum of the four scans). Secondary end points included
`the cumulative number of new Gd+ lesions from week 4 to week 24 and the number of
`
`new/enlarging T2-hyperintense lesions at week 24. Additional end points included the
`number of new Tl—hypointense lesions at week 24, relapse rate, and disability
`progression as measured by EDSS.
`Results: A total of 257 patients were enrolled in the study; 64 patients each were
`randomly assigned to receive one of the three BG00012 doses and 65 patients to placebo.
`Approximately 90% of patients completed the 24-wcck treatment period. BG00012 (720
`mg/day) significantly reduced the mean number of new Gd+ lesions (the primary end
`point) compared with placebo. In addition, BG00012 reduced the cumulative number of
`new Gd+ lesions, the number of new/enlarging T2-hyperintense lesions, and the number
`of new Tl-hyperintense lesions, compared with placebo.
`Conclusion: BG00012 significantly reduces brain lesion activity as measured by MRI in
`patients with RRMS over 24 weeks of treatment.
`
`Page 2 of 6
`
`Page 2 of 6
`
`

`

`Safety of a Novel Oral Single-Agent Fumarate, BG00012, in Patients With
`Relapsing-Remitting Multiple Sclerosis: Results of a Phase 2 Study
`
`<<Please enter authors and afiiliations>>
`
`<<Character limit: 2500; Character count: I 716 >>
`
`Objective: To determine the safety and tolerability of BG00012, a novel single-agent oral
`fumarate, in patients with relapsing-remitting multiple sclerosis (RRMS).
`Methods: This was a randomized, double-blind, placebo-controlled, phase 2 clinical trial
`conducted at 45 clinical centers in Europe. Men and women 18 to 55 years of age were
`eligible for the study if they had a diagnosis of RRMS and an Expanded Disability Status
`
`Scale score between 0.0 and 5.0. Patients also must have had either 21 relapse within 12
`months prior to randomisation with lesions on cranial MRI consistent with MS, or had
`gadolinium-enhancing (Gd+) lesions on cranial MR1 within 6 weeks of randomisation.
`Patients received BG00012 120 mg by mouth (PO) once daily (120 mg/day), 120 mg PO
`three times daily (360 mg/day), 240 mg PO three times daily (720 mg/day), or placebo.
`The study consisted of 2 phases: a 24—week double—blind treatment phase followed by a
`24-week, blinded, safety-extension phase in which all patients received BG00012.
`Patients received physical exams and had haematological assessments and urinalysis
`during both phases. All adverse events (AEs) were reported, regardless of severity or
`relationship to study drug. Results of the treatment phase are reported and data are pooled
`among BG00012 dose groups.
`Results: Of 257 patients enrolled, 176 (92%) BG00012 patients and 59 (91%) placebo
`patients completed the 24-week treatment phase. The most common AEs were flushing
`headache, nasopharyngitis, and nausea. The overall incidence of infection was similar in
`patients treated with BGOOOl2 and patients treated with placebo.
`Conclusion: BG00012 was safe and well tolerated in RRMS patients over 24 weeks of
`treatment.
`
`Page 3 of 6
`
`Page 3 of 6
`
`

`

`From:
`Sent:
`
`T0:
`Subject:
`
`"ludwig kappos" <lkappos@uhbs.ch>
`Tue Jan 31 2006 19:05:26 EST
`
`<gilmore.oneill(2:ibiogenidec.com>;
`Antw: C1900 ENS abstracts
`
`Dear Gilmore
`
`I also enjoyed the meeting and having some time to discuss issues of the BG 1 2 program with you and Al. We had a
`wonderfull trip by the everglades to Miami.
`1 have reviewed the absn‘acts and find them fine; have added some suggestions as attached.
`Best regards
`Ludwig
`
`>>> Gilmore O'Neill <Gilmore.ONeill@biogenidee.com> 31.01.2006 22:05:01 >>>
`Dear Ludwi g.
`
`it was good to see you and to meet Sofia at the National Faculty Meeting.
`1 am now inspired to start bringing my children with me to meetings when
`they are older.
`
`Thank you for your help and advise with the presentation of the "top line"
`C1900 data.
`
`lhave attached two draft abstracts on the 24 week C1900 data Would you
`be able to review them and make whatever changes or suggested changes that
`you like. I have left out the specific numbers and data so that they be
`freshly presented at ENS.
`
`If you send it back to me. I could disseminate it to the other members of
`the SAC. Iwill also ask Rachel to pull out the Steering C ommitee charter
`section on authorship that was agreed at the inaugural meeting, I will
`also ask her to find the names of the highest recruting investigators, per
`the charter section. Would that be okay with you?
`
`Best regards
`
`Gilmore
`
`PS Hope that your drive along Alligator alley was interesting.
`
`Gilmore N. O'Neill, M.B., M.R.C.P.1., M. Med. Sci.
`Director
`
`Clinical Development-Neurology
`biogcnidcc
`14, Cambridge Center, Bio 4
`Cambridge, MA 02142
`Tel: 617-679.2000
`Fax: 617—679—3518
`
`- ENS BG00012 safety in MS abs 3_LK.doc
`
`- ENS BGOOOIZ efficacy in MS abs 3_LK.doc
`
`Page 4 of 6
`
`Page 4 of 6
`
`

`

`Efficacy of a Novel Oral Single—Agent Fumarate, BG00012, in Patients with
`Relapsing-Remitting Multiple Sclerosis: Results of a Phase 2 Study
`
`<<Please enter authors and afiiliations>>
`
`<<Character limit: 2500; Character count: 2169>>
`
`Objective: To determine the efficacy of three dose levels of BG00012, a novel oral
`fumarate preparation, on brain lesion activity as measured by magnetic resonance
`imaging (MRI) in patients with relapsing-remitting multiple sclerosis (RRMS).
`Methods: This was a randomized, double—blind, placebo—controlled clinical trial of
`BG00012 in patients with RRMS. Men and women 18 to 55 years of age were eligible
`for the study if they had a diagnosis of RRMS and an Expanded Disability Status Scale
`
`(EDSS) score between 0.0 and 5.0. In addition, patients must have had either 21 relapse
`within 12 months prior to randomization or gadolinium-enhancing (Gd+) lesions on
`cranial MRI at screening. Patients received BGOOOl2 120 mg by mouth (PO) once daily
`(120 mg/day), 120 mg three times daily (360 mg/day), 240 mg three times daily (720
`mg/day), or placebo for 24 weeks. The treatment period was followed by a 24—week dose—
`blinded safety-extension period during which all patients received BG00012. The
`primary end point was the total number of Gd+ lesions over four MRI scans at weeks 12,
`16, 20, and 24 (calculated as the sum of the four scans). Secondary end points included
`the cumulative number of new Gd+ lesions from week 4 to week 24 and the number of
`
`new/enlarging T2—hyperintense lesions at week 24. Additional end points included the
`number of new Tl-hypointense lesions at week 24, relapse rate, and disability
`progression as measured by EDSS.
`Results: A total of 257 patients were enrolled in the study; 64 patients each were
`randomly assigned to receive one of the three BGOOOlZ doses and 65 patients to placebo.
`Approximately 90% ofpatients completed the 24-week treatment period. BGOOOl2 (720
`mg/day) significantly reduced the mean number of new Gd+ lesions (the primary end
`point) compared with placebo. In addition, BG00012 reduced the cumulative number of
`new Gd+ lesions, the number of new/enlarging T2-hyperintense lesions, and the number
`of new Tl-hypointense lesions, compared with placebo.
`Conclusion: BG00012 significantly reduces brain lesion activity as measured by MRI in
`patients with RRMS over 24 weeks of treatment.
`
`Page 5 of 6
`
`Page 5 of 6
`
`

`

`Safety of a Novel Oral Single-Agent Fumarate, BG00012, in Patients With
`Relapsing-Remitting Multiple Sclerosis: Results of a Phase 2 Study
`
`<<Please enter authors and afiiliations>>
`
`<<Character limit: 2500; Character count: I 716 >>
`
`Objective: To determine the safety and tolerability of BG00012, a novel oral fumarate
`preparation, in patients with relapsing-remitting multiple sclerosis (RRMS). (Add
`something about mode of action and long term safety data in psoriasis?)
`Methods: This was a randomized, double—blind, placebo—controlled, phase 2 clinical trial
`conducted at 45 clinical centres in Europe. Men and women 18 to 55 years of age were
`eligible for the study if they had a diagnosis of RRMS and an Expanded Disability Status
`
`Scale score between 0.0 and 5.0. Patients also must have had either 21 relapse within 12
`months prior to randomisation with lesions on cranial MRI consistent with MS, or had
`gadolinium-enhancing (Gd+) lesions on cranial MRI within 6 weeks of randomisation.
`Patients received BG00012 120 mg by mouth (PO) once daily (120 mg/day), 120 mg
`three times daily (360 mg/day), 240 mg three times daily (720 mg/day), or placebo. The
`study consisted of 2 phases: a 24-week double-blind placebo controlled treatment phase
`followed by a 24-week, dose blinded, safety-extension phase in which all patients
`received BG00012. Patients received physical exams and had haematological
`assessments and urinalysis during both phases. All adverse events (AEs) were reported,
`regardless of severity or relationship to study drug. Results of the treatment phase are
`reported and data are pooled among BG00012 dose groups.
`Results: Of 257 patients enrolled, 176 (92%) BG00012 patients and 59 (91%) placebo
`patients completed the 24-week treatment phase. The most common AEs were flushing
`headache, nasopharyngitis, and nausea. The overall incidence of infection was similar in
`patients treated with BG00012 and patients treated with placebo.
`Conclusion: BG00012 was safe and well tolerated in RRMS patients over 24 weeks of
`treatment.
`
`Page 6 of 6
`
`Page 6 of 6
`
`