1、Global BioPharma 2019 SMA Physician Survey TakeawaysSee the end pages of this presentation for analyst certification and important disclosures,including non-US analyst disclosures.J.P.Morgan does and seeks to do business with companies covered in its research reports.As a result,investors should be
2、aware that the firm may have a conflict of interest that could affect the objectivity of this report.Investors should consider this report as only a single factor in making their investment decision.Global Equity ResearchSeptember 2019Cory W.Kasimov AC212-622-Neena M Bitritto-Garg,CFA212-622-8967nee
3、na.m.bitritto-Matthew T Holt,Ph.D.212-622-Gavin Scott212-622-US BiotechnologyConference Call DetailsTuesday,September 24 11:00am ET /16:00pm UKContact us or your J.P.Morgan sales representative for details.Eric Joseph AC212-622-Turner Kufe,MD212-622-Daniel Wolle212-622-US SMID Biotechnology Jessica
4、Fye AC212-622-Yuko Oku212-622-EU Pharma&BiotechRichard Vosser AC(44-20)7742-James D Gordon(44-20)7742-James P Quigley(44-20)7742-Sarita Kapila(MD)(44-20)7134-Laerke L Engkilde(44-20)7742-2917 2We surveyed 26 physicians(19 US,7 EU)who collectively treat 1,100 SMA patients,prescribe Spinraza,and are f
5、amiliar with the SMA development-stage pipeline.Overall,physicians are satisfied with Spinraza(7.4/10)but see room for improvement on multiple fronts,including dosing&administration and costand as such,new therapies have the potential to take material market shareWhen considering a future market whe
6、re Spinraza,gene therapy,and orals are all available,physicians estimate a 14%relative reduction from today in the proportion of patients on Spinraza looking out 5 years(slide 38),implying over$290M at risk(if taken at face value)When asked directly about the potential impact of risdiplam,docs note
7、that over 50%of Spinraza patients could ultimately be switched to an oral if data are comparable or betterfor the oral therapy;even up to one-third of patients could be switched if data are even slightly inferiorSurveyed physicians are thus far prescribing Zolgensma to 21 commercial patients(12 Type
8、 1,7 Type 2&2 Type 3)in the US.They expect use to be greatest in younger Type I and II patients,but longer-term use by these physicians is below current market expectations of 100%use in incident patients.Use in 30%of prevalent patients seems in line with current expectationsUnsurprisingly,efficacy
9、is the most important consideration in choosing Zolgensma,and importantly,most doctors are not concerned about the data manipulation in the US filingBy the end of the year,US physicians expect to be using the product in 17%of their Type 1 patients,and they expect to use Zolgensma in around 53%of new
10、born patients.Extrapolating this data implies sales of c.$300m in 2019,which implies consensus forecasts in 2019 of$284m should be underpinnedLonger-term,physicians expect to use Zolgensma in only 56%of newborn Type I patients and 42%of newborn Type II patients,suggesting that longer-term forecasts
11、could be challenging to meet.Use in only this proportion of newborn patients,if replicated,would only represent$1bn in sustainable revenuesResults affirm general excitement around the potential entry of oral SMA therapy,risdiplam in particular,with a focus on potential dosing advantages compared wit
12、h Spinraza(especially in older/non-juvenile patients)and lower cost.That said,physicians seek/await additional data to fully understand risdiplams clinical potentialIn general,physicians believe the clinical data to date indicate that risdiplam is comparably effective to Spinraza(38%)or that it is p
13、remature to determine which has the superior efficacy profile(31%)While present survey results would suggest 35%penetration for risdiplam broadly across SMA within 5 years,we believe data from Part 2 study portions of SUNFISH(Type 2/3;pbo-controlled)and FIREFISH(Type 1)will be important to clarifyin
14、g/solidifying risdiplams positioning within the treatment landscapeKey TakeawaysSurvey highlights key risks to continued growth for Spinraza,sets launch expectations for Zolgensma,and provides early thoughts on risdiplamSource:J.P.Morgan Research3Biogen(BIIB,N,covered by Cory Kasimov)Despite first-m
15、over advantage and a very strong launch,Spinraza market share may be approaching a peak and could decline after 2020+due to competitive threats and more convenient therapies,namely orals such as risdiplam.While this does not come as a surprise given the burden of dosing Spinraza,we dont think the ri
16、sks are fully reflected in consensus numbers.Physicians estimate that in 5yrs,the proportion of SMA pts on Spinraza could contract by 14%($290M in sales at risk based off of FY19 consensus),but this could be much greater if oral efficacy pans out.Nevertheless,2024 consensus estimates still imply som
17、e measure of growth.Combined with continued market pressures on the MS front,we believe the near-to intermediate-term outlook for BIIB shares remains challenged as the Street continues to better appreciate risks to the business.Novartis(NOVN,UW,covered by Richard Vosser)Zolgensma near-term forecasts
18、 seem underpinned,longer-term Zolgensma could struggle to sustainably meet expectations:The survey responses call into question the market expectation(and ours)that Zolgensma will hoover up 100%of incident patients across both Type I&II SMA.In fact if the responses of 56%ultimate use in Type I&II ne
19、w born patients is borne out across the market then this would suggest a sustainable revenue opportunity of only$1bn(at$2m a patient globally).Although there would be some remaining contribution from prevalent patients in 2023,consensus forecasts of$1.9bn in 2023 could be challenging based on this s
20、urvey.However,in the near term the survey suggests 2019 forecasts are underpinned with a potential across incident and prevalent SMA patients 24 months19-24 months13-18 months7-12 months0-6 months8%11%14%15%12%17%20%8%60%52%80%All(n=26)US(n=19)EU5(n=7)18+yr11-17 yr6-10 yr3-5 yr0-2 yr10%14%21%26%11%1
21、6%18%11%16%17%13%38%25%62%All(n=26)US(n=19)EU5(n=7)Type IIType IIIType I10How many of your SMA Type I,II,and III patients fall into the following age ranges?Using the information collected in the question shown on slide 9,we estimated the proportion of patients that are pediatric(66%)vs.adult(34%);w
22、e assumed all Type I patients are pediatricBiogen estimates that 60%of the SMA patients in the US are adults(with 20%on Spinraza as of the end of 2Q19),and has flagged increasing penetration in the adult population as a key area of focusJPM View:Though Biogen has flagged a higher proportion of adult
23、 patients in the US(60%adults vs.26%in the survey),many of those(especially with Type III disease)may not be currently seeking active treatment from a physician(due to milder disease)Adult patients make up only about one-third of the patients treated by surveyed physiciansSMA Patient Breakdown,Pedia
24、tric vs.AdultSource:JP Morgan Research66%74%49%34%26%51%All(n=26)US(n=19)EU5(n=7)AdultPediatric11How many of your patients with each type of SMA are currently treated with each of the following?43%of SMA patients under care are on Spinraza today(41%US,49%EU),with use relatively consistent across typ
25、es;Biogen indicated on the 2Q19 earnings call that the total US market was 30%penetratedSurveyed physicians have 85 total patients under care who have taken Zolgensma,21%of whom(18 patients)are also on Spinraza,though only 1/3 of the patients(28)received Zolgensma in the commercial setting(see slide
26、 12)50%of SMA pts are currently untreated(55%in the US,41%EU),with some having previously taken Spinraza(14%discontinuation rate implied)JPM View:Use trends for Spinraza overall and across pt subtypes are consistent with expectations,given that intrathecal dosing makes it more difficult to administe
27、r to older patients(Types II and III).Commercial use of Zolgensma in the US physicians surveyed had reached 12 Type I patients,7 Type II patients,and 2 Type 3 patients at the time of the surveySpinraza is currently used in 40%of SMA patients under care,and Zolgensma use is starting to pick upCurrent
28、 Treatment BreakdownSource:JP Morgan Research39%44%42%42%37%41%37%38%44%49%53%49%12%5%3%6%9%3%2%5%18%9%4%10%4%2%5%2%2%7%7%7%7%8%8%11%9%6%5%3%39%43%48%43%41%46%50%46%32%37%43%38%Type IType IIType IIITotalType IType IIType IIITotalType IType IIType IIITotalAll Docs(n=26)US(n=19)EU5(n=7)Has never taken
29、 eitherSpinraza or ZolgensmaNot on either,butPREVIOUSLY on SpinrazaBOTH Spinraza+ZolgensmaZolgensma ONLYSpinraza ONLY12For your patients that have taken Zolgensma,how many did so in a clinical trial versus the commercial setting?Most patients who have taken Zolgensma so far have done so as part of a
30、 clinical trial(not surprising given timing of approval)In the US,surveyed physicians have 21 patients on commercial Zolgensma,12 who have Type I disease,7 with Type II,and 2 with Type III as the label covers all patient regardless of SMN2 copy number.In Europe,physicians indicated they have 7 patie
31、nts who have taken Zolgensma commercially,5 who have Type I disease and 2 with Type III diseaseJPM View:In the US,we expected that the bulk of patients would be Type I getting commercial Zolgensma,while in Europe,no patients have gotten commercial drug given that it is not yet approved;physicians ma
32、y have included patients in expanded access programs in the“commercial”bucketMost patients who have taken Zolgensma have done so in a clinical trial setting,though our survey may have picked up some commercial useZolgensma Commercial Vs.Trial UseSource:JP Morgan Research32 18 7 57 21 6 4 31 11 12 3
33、26 17 7 4 28 12 7 2 21 5-2 7 Type IType IIType IIITotalType IType IIType IIITotalType IType IIType IIITotalAll Docs(n=26)US(n=19)EU5(n=7)Took Zolgensma in a clinical trialTook commercial Zolgensma13SURVEY RESULTS:SPINRAZA THOUGHTS&TRENDS14On a scale from 1 to 10,how would you describe your experienc
34、e using Spinraza overall and for each type of SMA?(1=worst,10=best)Overall,physicians are satisfied with Spinraza(7.4/10),with satisfaction highest in Type I patients,especially younger patients prior to achievement of major motor milestones,and lowest in Type III and older patients due to the trade
35、off between dosing and administration burden and efficacyJPM View:Were not surprised by the results given the strength of the data in Type I vs.the other types and the administrative burden in older patients(with milder disease)Physicians are overall highly satisfied with their Spinraza use experien
36、ce,with satisfaction higher for use in Type I versus Types II and IIIOverall Satisfaction with SpinrazaSource:JP Morgan ResearchSelect Comments on Overall Satisfaction with SpinrazaIt has been a well tolerated and effective approach for most SMA patients of mine.Compliance has also remained high.Mil
37、d to modest clinical efficacy in early Type I,mild at best efficacy in Type 2-3Works best in younger patients and in SMA type I patients.Difficult to administer intrathecally to spinal surgery patientsSMA 2 still ambulatory patients have a good outcome.A little bit complicated in SOME SMA I because
38、of the need for continuative follow-upI am satisfied for the treatment of children with SMA but much less in adult patientsSee better results with younger patients,as expectedIt has helped but is not a cureAppears to be effective,some issues with administrationThe earliest Spinraza is given,the best
39、 results-thats why the results tend to be more impressive(and the satisfaction higher)in patients with SMA I/II treated early.Many of my SMA type III patients started Spinraza at a later stage of the disease(already in adulthood,wheelchair bound).Even in those patients we were able to appreciate som
40、e meaningful gains,though not as impressive as the early pediatric patients(24 moSpinraza ONLYZolgensma ONLYBOTH Spinraza+ZolgensmaAll docs(n=26)27Please indicate the likely proportion(%)of Type II and III SMA patients you ultimately anticipate prescribing Spinraza and/or Zolgensma to,by ageZolgensm
41、a prescribing is expected to be more limited in Types II and III versus Type I(slide 26)The patient population expected to see highest Spinraza penetration rates is Type II adolescent and adult patients(68%prescribed Spinraza at peak)JPM View:Results are consistent with what would be expected;becaus
42、e Biogens stated goal is to increase penetration into the adult Type II and III populations,these results are promising,but we continue to expect uptake in Type III patients(who tend to have mildest disease)to be challenging given complications with and burden of administration.For Zolgensma,42%of T
43、ype II newborns represents c.$300m in recurring revenue and 38%of Type III newborns c.$80m in recurring revenue.Across all types the survey suggests c.$1bn in sustainable revenue across Type I/II/III,which is below longer-term expectations.Consensus forecasts sales of$1.9bn in 2023(JPMe$1.4bn).Spinr
44、aza use is expected to be the highest in Type II patients,while use in Type III patients is more limited due to efficacy/burden tradeoffZolgensma&Spinraza Peak Prescribing by Age,Types II and IIISource:JP Morgan Research;weighted average(by#pts under care)All docs(n=26)49%51%55%24%19%23%18%11%13%New
45、ly diagnosed Type II pts Pediatric Type II pts alreadyidentifiedAdolescent/adult Type IIpts already identifiedSpinraza ONLYZolgensma ONLYBOTH Spinraza+ZolgensmaType IIType III43%48%49%24%20%21%14%12%11%Newly diagnosed Type IIIptsPediatric Type III pts alreadyidentifiedAdolescent/adult Type IIIpts al
46、ready identifiedSpinraza ONLYZolgensma ONLYBOTH Spinraza+Zolgensma28How do you plan to use Spinraza in patients that you have prescribed or plan to prescribe Zolgensma to?Most physicians(nearly 70%)expect to use Spinraza for at least some patients who have taken ZolgensmaThis reaffirms results on sl
47、ide 11,which showed that 21%of pts under care of a surveyed physician who had taken Zolgensma are also on Spinraza todayJPM View:This is consistent with our expectations given that some patients in the Zolgensma studies were on Spinraza and the fact that durability of Zolgensmas effect is unclear;th
48、e bigger hurdle to co-administration of the products in the commercial setting will be reimbursement/accessMost physicians expect to use Spinraza for at least some of their patients who have taken Zolgensma Spinraza and Zolgensma Co-AdministrationSource:JP Morgan Research4%5%19%21%14%46%47%43%31%26%
49、43%All(n=26)US(n=19)EU5(n=7)Does not plan to use Spinraza with ZolgensmaPlans to use Spinraza in SOME Zolgensma ptsPlans to use Spinraza in MOST Zolgensma ptsPlans to use Spinraza in ALL Zolgensma pts29SURVEY RESULTS:RISDIPLAM&PIPELINE THOUGHTS30What clinical-stage therapy in development for SMA are
50、 you most excited about?Nearly half of surveyed physicians(46%)indicated that they are most excited about risdiplam,with another 12%citing branaplam and 8%citing SRK-015Regulatory applications for risdiplam are expected to be submitted in the US this year and in Europe in 1H20JPM View:This is consis
