Perc

ent of D

MT

-tre

ate

d p

atie

nts

RealTime Dynamix™: Multiple Sclerosis (US) Q2 2018

PPMS DMT Treatment Rate

Ocrevus, with its first-to-market primary progressive MS (PPMS) label, has had a material impact on the self-reported PPMS treatment

rate. In the most current report, the PPMS treatment rate now appears to be stable following an increasing trend that began in Q1 2017.

The active secondary progressive MS (SPMS) treatment rate also appears to have stabilized at a level close to that for relapsing remitting

MS, following consistent increases since early in the Ocrevus launch. The treatment rate plateau is in line with the active SPMS share of

Ocrevus-treated patients, having dropped back slightly compared to the prior quarter, with a greater share instead going to PPMS.

RealTime Dynamix™: Multiple Sclerosis (US) is a quarterly report series providing insights about the evolving DMT market. Participating neurologists are recruited from the Spherix Network, a proprietary panel of more than 600 neurologists managing at least 25 patients with MS. The next wave of research will be published in September 2018. For more information contact: info@spherixglobalinsights.com

Finally, for the not active SPMS patient segment, the treatment rate has remained low with no observable impact from the Ocrevus

launch due to minimal (and decreasing) use in the subtype.

PPMS Share of Ocrevus-Treated Patients

Percent of patients

Active SPMS DMT Treatment Rate Active SPMS Share of Ocrevus-Treated Patients

Perc

ent of D

MT

-tre

ate

d p

atie

nts

Perc

ent of patie

nts

Not Active SPMS DMT Treatment Rate Not Active SPMS Share of Ocrevus-Treated Patients

Perc

ent of D

MT

-tre

ate

d p

atie

nts

Perc

ent of patie

nts

*Statistically significant

difference from 2016, 2017

*

*Statistically significant

difference from 2018

*

In order to address the underrepresentation of these commercial-relevant MS subtypes, Spherix Global Insights will be conducting

RealWorld Dynamix: Progressive Forms of MS, a high quota patient audit where neurologists will submit up to seven of their most

recently seen DMT-treated PfMS patients regardless of where they are in their DMT treatment sequencing. The audit provides a

unique opportunity to focus on these subtypes to understand what drives therapy initiation and prescribing decisions, as well as

assess the opportunity for key DMTs in development for PfMS.

Similarly, in the recent RealWorld Dynamix: DMT Switching in MS, neurologists submitted 1,035 patient records of their most recent

patients switched to a different DMT within the past three months. Of these, only 21% were from PfMS, with active SPMS the most

prevalent, making analysis of the under-treated not active SPMS subtype difficult.

In the recent RealWorld Dynamix: DMT New Starts in MS, neurologists submitted up to seven patient records for MS patients initiated

on their first disease-modifying therapy (DMT) within the past 3 months. While 1,033 patient records were collected, only 14% were

progressive forms of MS (PfMS) patient records making strong conclusions regarding drivers of treatment patterns difficult to assess.

Does your team get it? Contact info@spherixglobalinsights.com

or call (484) 879-4284 for more information.

First-Line DMT Brand by MS Subtype

The question remains “Why would a SPMS patient initiate their first DMT after a SPMS diagnosis?”

Switch DMT Brand Allocation by MS Subtype

Active SPMS

Perc

ent of patie

nts

With a higher sample, does tolerability really drive more of not active SPMS switches compared to other PfMS subtypes?

Perc

ent of patie

nts

Caution: small sample

PPMS Not active

SPMS

What questions would you like answers to?

To order or to get more information, please contact

info@spherixglobalinsights.com or call (484) 879-4284

Multiple Sclerosis (US)

Products Profiled

Commercial Products

Bayer (Betaseron), Biogen [Avonex, Plegridy, Tecfidera, Tysabri, Zinbryta (with AbbVie)], EMD Serono (Rebif), Genentech (Ocrevus, Rituxan), Genzyme (Aubagio, Lemtrada), Mylan (generic glatiramer acetate), Novartis (Gilenya, Extavia), Sandoz (Glatopa), Teva (Copaxone)

Pipeline Agents

AB Science (masitinib), Biogen [opicinumab, ALKS 8700 (with Alkermes)], Celgene/Receptos (ozanimod), J&J/Actelion (ponesimod), MedDay (MD-1003), Merck Serono (Mavenclad), Novartis (siponimod, ofatumumab), TG Therapeutics (ublituximab)

Key Dates

• Q1 March

• Q2 June

• Q3 September

• Q4 December

Note: a three day embargo is placed on delivery to non-manufacturers allowing clients time to digest the

findings before public dissemination

Deliverables

• PowerPoint report

• Frequency table & summary statistics

• On-site presentation

• Proprietary questions (for purchasers

of the annual series)

Related Reports 2018

• RealTime Dynamix™: Multiple

Sclerosis EU

• RealWorld Dynamix™: DMT

Switching in Multiple Sclerosis US

• RealWorld Dynamix™: DMT New

Starts in Multiple Sclerosis US

• RealWorld Dynamix™: Progressive

Forms of Multiple Sclerosis US

OVERVIEW

The US multiple sclerosis (MS) market is more dynamic and complex than ever with several clinically distinct disease-modifying therapies (DMTs) currently available, including Genentech’s Ocrevus for primary progressive MS (PPMS) as well as relapsing forms of MS (RMS), and an active late-stage DMT pipeline. In addition, building on the first generic DMT launch in 2015, the availability of multiple generic glatiramer acetate options, as well as the possibility of oral generics over the next few years, will result in a major future shift in the landscape in the face of increasing payer pressure. RealTime Dynamix™: Multiple Sclerosis (US) provides a close-quarters analysis of key performance metrics, focusing on brand gains and losses, industry contact rates, familiarity and adoption rates of recently launched products, and awareness of products in development. Product perceptions, disease awareness and attitudes, practice management and other topics are rotated throughout the year to provide an ongoing probe of the crucial drivers of change. This ongoing, independent insights series allows marketing professionals to keep abreast of and quickly react to market changes by providing critical information that will support their commercial strategies in the MS space.

SAMPLE & METHODOLOGY

Each quarter, ~100 US neurologists provide their responses to an online survey. Respondents are recruited from the Spherix Network, a proprietary group of clinical neurologists meeting our strict screening criteria. Our relationship with this network leads to more engaged respondents resulting in higher quality output. Additionally, this gives us the opportunity to more easily revisit physicians in order to uncover even more insight on strategically important findings.

KEY QUESTIONS ANSWERED

• How is the current and near-term landscape for the MS market evolving?

• What are the critical opportunities and barriers to growth for each brand and

class?

• How is Ocrevus impacting the RMS and PPMS markets?

• How is the availability of multiple generic glatiramer acetate agents impacting

the market? To what extent is use driven by neurologist choice versus payer mandate?

• How is the treatment algorithm changing with increasing oral DMT experience

and expanding options within the monoclonal antibody DMT class?

• To what degree do neurologists have strong preferences for specific brands

within the DMT classes? How are the DMTs delivering on the key attributes and on typical patient types?

• With fewer opportunities for personal interactions, what the best channels for

industry to share product information with neurologists?

• How often are patients requesting specific DMT brands?

• What are neurologists’ perceptions of late-stage pipeline assets and how do

they anticipate incorporating these products into their MS treatment?

Products Profiled

Commercial Products

Bayer (Betaseron), Biogen [Avonex, Plegridy, Tecfidera, Tysabri], EMD Serono (Rebif), Genentech (Ocrevus, Rituxan), Genzyme (Aubagio, Lemtrada), Mylan (generic glatiramer acetate), Novartis (Gilenya, Extavia), Sandoz (Glatopa), Teva (Copaxone)

Pipeline Agents

AB Science (masitinib), Biogen [opicinumab, BIIB098 (with Alkermes)], Celgene/Receptos (ozanimod), J&J/Actelion (ponesimod), MedDay (MD-1003), Merck Serono (Mavenclad), Novartis (siponimod, ofatumumab), TG Therapeutics (ublituximab)

Key Dates

• November Publication

Note: a three day embargo is placed on delivery to non-manufacturers allowing clients time to digest the findings before public dissemination

Deliverables

• PowerPoint report

• Frequency table & summary statistics

• On-site presentation

• Access to de-identified database

through Spherix analytics team

• Proprietary questions

Related Reports 2018

• RealWorld Dynamix™: DMT Switching

in Multiple Sclerosis US

• RealWorld Dynamix™: DMT New

Starts in Multiple Sclerosis US

• RealTime Dynamix™: Multiple

Sclerosis US

• RealTime Dynamix™: Multiple

Sclerosis EU

Progressive Forms of Multiple Sclerosis (US)

To order or to get more information, please contact

info@spherixglobalinsights.com or call (484) 879-4284

OVERVIEW Multiple sclerosis (MS) patients with progressive forms of MS (PfMS) have historically low disease-modifying therapy (DMT)-treatment rates due to a lack of therapies approved for PfMS and an anticipated lack of response to DMTs approved for relapsing forms of MS (RMS). With the FDA approval of Genentech’s Ocrevus as the first DMT for the treatment of primary progressive multiple sclerosis (PPMS), US neurologists now have an option for one of the PfMS subtypes. However, an unmet need remains for DMTs shown to be effective for secondary progressive MS (SPMS), a niche that products in the late-stage SPMS pipeline, including Novartis’ siponimod, MedDay’s MD-1003, and AB Science’ masitinib, are attempting to address. With the availability of an approved DMT and potentially more on the horizon, it is imperative to understand the current treatment algorithm for PfMS including how patient characteristics and neurologist perceptions influence the decision to initiate or switch DMT and the resulting brand selection. Understanding when, why, and to which product a neurologist will prescribe for a PfMS patient is critical to building an effective commercial strategy for both first-line and later-line therapies targeting this patient population. RealWorld Dynamix™: Progressive Forms of MS (US) blends attitudinal and demographic physician survey data with patient record data to uncover how practice type and setting and certain beliefs influence the treatment pathway and to understand how marketed DMTs are being used by physicians and for what PfMS patient types. The report also captures physician’s perspectives about products in development and the impact they will have on the current treatment paradigm among PfMS patients.

SAMPLE & METHODOLOGY Spherix Global Insights conducts an online survey with ~200 US neurologists combined with a large-scale patient record audit of over 750 of their MS patients that are diagnosed with a PfMS (n=±250 each for active SPMS, not active SPMS, or PPMS) and are currently treated with a DMT. Each neurologist completes an in-depth retrospective review of their last 3-7 patients who meet specific study criteria. Respondents are recruited from the Spherix Network, a proprietary group of clinical neurologists meeting our strict screening criteria. Our relationship with this network leads to more engaged respondents resulting in higher quality output. Additionally, this gives us the opportunity to more easily revisit physicians in order to uncover even more insight on strategically important findings.

KEY QUESTIONS ANSWERED • What is the self-reported treatment rate for active SPMS, not active SPMS, and

PPMS? What are the reasons for not treating patients with a DMT?

• What clinical assessments or tests are used to help identify when a relapsing-remitting

patient has transitioned to SPMS?

• What are the most frequently prescribed agents for active SPMS, not active SPMS,

and PPMS? How does line of therapy for these DMTs differ between secondarily progressing MS versus primarily progressing MS?

• What are the key drivers (e.g., efficacy/safety/tolerability/patient/payer) for DMT

selection?

• What is the profile of a previously treatment-naïve PPMS patient being started on an

injectable vs. oral vs. monoclonal antibody DMT?

• Among patients on a second line or later DMT, how does switching decisions differ

between active SPMS, not active SPMS, and PPMS patients? If previously treated, are SPMS patients typically switched to a different DMT following confirmed transition from RRMS to SPMS?

• What is the opportunity cost for each brand (e.g., where would their brand have been

selected if the first choice was not available)?

• Are neurologists willing to sacrifice safety for more efficacy in certain populations of

MS patients?

• What is the patient profile for a likely patient candidate for siponimod? ozanimod? MD-

1003? Masitinib?