E-VokOL-utionThe evolution of VoKOL

VoKOL 1.10Favorable Efficacy VoKOLs

• “Gilenya-like, this changes everything”• “The enthusiam and interest among my patients is so high”• “DMF has better efficacy than all agents except Tysabri”

April 5, 2013

VoKOL 1.0Favorable Safety/Tolerability VoKOLs

• “Like the lack of drug interactions and contraindications”• “May be the easiest MS drug to initiate with patients.”• “Key advantage to initiating Tecfidera treatment is the lack of required monitoring”

April 5, 2013

VoKOL1.0Unfavorable Safety/Tolerability VoKOLs

• “I am concerned that titration recommendation in PI is too short”• “I will monitor CBC more frequently than yearly.• “Concerned about GI side effects, especially diarrhea”• “Tecfidera is an immunosuppressant so the risk of infection will be there.” • “Long-tem safety is a concern”

April 5, 2013

VoKOL 2.0:Tecfidera GI Side Effects

Aug 2013 Sep 2013 Oct 2013 Nov 2013 Dec 2013 Jan 2014

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Efficacy Research/IIT Safety Flushing GI

What KOLs are saying (VoKOLs) What MLs are discussing

• KOLs report 5-10% d/c rate due to GI tolerability• Those with more patients report lower dc rates. • Higher rate of GI complaint VoKOLs early after approval,

lower rate of complaint VoKOLs since November.• 10% of patients discontinuing Tecfidera despite longer

titration period – August 2013• “GI events are manageable...we educate patients about

the time course of GI symptoms and by 8-10 days after achieving the full dose, patients are fine” – November 2013

• KOL mitigations: Full meal, Applesauce, Peanut Butter, Probiotics, H2 Blockers or PPI, Immodium with Simethicone, Pepto-bismol, Zofran, dose-titration

• GI tolerability 2nd most common discussion (efficacy #1)• Most common references cited in response to questions:

• Meltzer GI Tolerability DEFINE and CONFIRM AAN 2013 POSTER

• Phillips GI Flushing management strategies expert panel ECTRIMS 2013 POSTER

• Data Gaps • “How to manage abdominal pain”• “How to best titrate to avoid GI” issues”

* Size of bubble = frequency of VoKOL report

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VoKOL 3.0GI Tolerability US KOL Perceptions

Global Medical Sentiment Key (US ENGLISH)

(1.1) -- (0.7) (0.4) -- (0.2) (0.15) -- (0.10) (0.05) -- 0.08 0.2 -- 0.4 0.7 -- 1.0 >1.4<(1.1) (0.7) -- (0.4) (0.20) -- (0.15) (0.10) -- (0.05) 0.08 -- 0.2 0.4 -- 0.7 1.0 -- 1.4

KOL Perception by Region KOL Perception by State

• This chart represents KOL Perception by state and region based on MSL outreach between 10/22 – 10/24.

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.057