J.P 摩根-美股-生物科技行业-北美中小型生物科技公司研究-2019.3-28页.pdf

1J.P.Morgan SMID Biotech ResearchMyovant(MYOV)/ObsEva(OBSV):Results from Our US Physician Survey on the GnRH-R Antagonist LandscapeSee 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 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.North America Equity ResearchMarch 2019J.P.Morgan Securities LLCEric Joseph AC212-622-US SMID Biotechnology 2Key GnRH Survey TakeawaysSource:J.P.Morgan ResearchEarly but promising outlook for the GnRH Receptor Antagonist landscape in endometriosisWhile still early days into the Orilissa launch,physicians indicate moderate-to-high level of satisfaction with product profile inendometriosis(EM)Surveyed patient base implies current Orilissa share 6-8%Greater overall satisfaction with the higher dose(200mg BID)regimen,driven by onset and overall efficacyNearly all surveyedphysicians expecting to incorporate GnRH-RA use into practice over next 6 to 12 monthsOn the payer side,only 35%have completed formulary reviews to date,of those 75%offering coverage with/without PAAnticipating robust uptake across the GnRH-RA landscapeas the marketexpands with new entrants(relugolix,linzagolix)Directional support for immediate uptake of relugolix(Myovant)and linzagolix(ObsEva)at their respective launchesOverall GnRH-RA uptake expected to happen largely at the expense of oral contraceptive useSomewhat surprisingly,surgery/invasive procedures are expected to maintain strong foothold in treatment paradigmFavorableoutlook on averageduration of therapy about 1-2 yearsExpectations for an average 1-2+year duration of therapy,descending with degree of estrogen suppressionMeaningfully high(45%)expectation of 1+year duration of higher-dose/potency regimens in combination with ABT(ahead of our current model at 70%of physicians indicate plans to use GnRH-RAs in UF practice(some indicating Orilissa use in UF today)High support for both short-tern use(6 months),before and after surgery,and long-term use as a surgery alternative however,longer-term datasets may be required to better establish product differentiationAnticipated patient preferences are roughly eventhe different potential GnRH-RA strengths(full vs partial E2 suppression)At this point,bleeding cessation and pain relief are higher priorities for docs,while pharmacology(DDI,titration andconvenience of add-back therapy)is a lesser concern3Company Specific TakeawaysSource:J.P.Morgan ResearchMyovant(MYOV)OW|$37 Dec-19 PT Core thesis continues unchanged,viewing relugolix as a clinically de-risked asset with the potential for meaningful valuecreation from a series of phase3 readouts over the next 9-12 months(UF/APC/EM)Readouts:Phase 3 LIBERTY UF-2Q&3Q19|Phase 3 HERO in APC 4Q19|Phase 3 SPIRIT EM 1Q20Results from our survey suggest broad level uptake of the GnRH-RA class in UFImplied duration of therapy in UF,particularly as an alternative to surgery,could serve as upside leverto street models1-year randomized withdrawal study portions to the ongoing LIBERTY and SPIRIT phase 3s could be a meaningdifferentiator to the GnRH-RA class,conferring maintenance potentialThus far,convenience of add-back administration not a particularly strong point of traction among treating physiciansObsEva(OBSV)OW|$30 Dec-19 PTWe continue to view linzagolix as meaningfully de-risked,underappreciated GnRH-RA asset,with a potentially best-in-classtolerability and dose optionality profileSurvey results reinforce our view of endometriosis/UF capable of supporting multiple GnRH-RA products,anticipatingcompelling linzagolix uptake despite likely third to market entrySimilarly to relugolix,reception and expectations around duration of use in UF serve as upside levers to street modelsPhysician agnosticism to the use of a partially E2 suppressive vs full E2/ABT combo regimens creates meaningful shareopportunity for linzagolix(assuming success for 100mg QD arm in PRIMROSE 1&2)Phase 3 PRIMROSE 2 data-4Q19|PRIMOSE 1-early 20204Survey BackgroundSource:J.P.Morgan ResearchBackgroundWe surveyed 30 US-based physicians20 obstetricians/gynecologists(67%);10 primary care physicians(33%)Physicians in both specialties averaged21 years of clinical practiceSurvey was conducted in March 2019On averagesurveyed physicians currently treat 100 EM patientsand 120 UF patientsOb/Gyns currently treating 120 EM patients and 135 UF patientsPCPs currently treating 70 EM patients and 95 UF patientsAll physicians were very familiar with the GnRH antagonistclass and either prescribe Orilissa,or plan to prescribe a GnRH-aOnly one Ob/Gyn was a clinical trial investigatorfor Orilissa/relugolix/linzagolixAll respondents(n=30)Ob/Gyns(n=20)PCPs(n=10)5Endometriosis Patient BackgroundSource:J.P.Morgan ResearchThe average EM patient age was 31.5 years of age,with fairly broad distribution in pain severitySurveyed Ob/Gyns tend to treat younger patients(30 years),whereas PCPs tend to treat slightly older patients(34.5 years)Ob/Gyns tended to have fewer moderate-to-severe patients that PCPs,perhaps reflecting better management of symptoms byspecialistsPercent EM Patients with Pain Severity6Current Treatment Preference for EMSource:J.P.Morgan ResearchPatients are currently being managed similarly by both OB/Gyns and PCPsOral contraceptives are the preferred treatment for both groups(45%)Followed by either Lupron(GnRH agonist)or NSAIDs/non-prescription med therapy6-8%are currently being treated with Orilissa,launched in 3Q18Other treatments specified by physicians include IUDs(n=3),depot contraceptives(n=1),progesational agents(n=1)All respondents(n=30)Ob/Gyns(n=20)PCPs(n=10)While a significant number of patients will likely undergo invasive surgical procedure within the next 6-12 months47%of Ob/Gyns,while only 25%of PCPs,expect their patients will undergo surgeryThe range of Ob/Gyns was from 1%to 100%7Physicians Experience with Orilissa to Date for Treating EMSource:J.P.Morgan ResearchPhysicians with higher satisfaction with Orilissa explained that it“works well”with a“favorable side effect profile”Physicians who were less satisfied cited efficacy concerns that Orilissa is“too similar to Lupron”or“not much advantage over oralcontraceptives”Multiple physicians thought Orilissa was cheap and had good coverage,while only one Ob/Gyn thought it was too expensiveResponses detailed in Appendix ARanking of Orilissa Clinical Dimensions(Ob/Gyns n=12,PCPs n=3)Overall,physicians expressed moderate to high satisfaction with OrilissaOf note,the 200 mg BID dose was ranked more highly than 150 mg QD on efficacy parameters,with similar satisfaction with respect toconvenience/compliance between dosing regimens,and tolerability being the limiting factorPCPs cited less satisfaction with Orilissa than Ob/Gyns,particularly the 150 mg QD dose on onset of action and overall efficacy8Plans to Prescribe Orilissa/GnRH Antagonists for EMSource:J.P.Morgan ResearchNearly all physicians not currently writing Orilissa indicate plans to do so within the next 12 monthsMost Ob/Gyns(75%)plan to prescribe within 6 months,while 60%of PCPs will prescribe in 6 monthsMost physicians are awaiting additional safety/efficacy before prescribing4 physicians(3 PCPs)are awaiting their colleagues opinion,while 5 others await additional safety/efficacydataNotably,one PCP plans to defer GnRH antagonist prescribing to gynecologistsFurther detail in Appendix CAll respondents(n=15)Ob/Gyns(n=8)PCPs(n=7)9Preferred GnRH Antagonist Profile for EndometriosisSource:J.P.Morgan ResearchOnset of pain relief and tolerability likely to dictate GnRH-RA product preference;dose flexibility and combinations with add-back are lower points of focusPhysicians rank ordered sevenmetrics(1=most important)as it relates to their GnRH antagonist prescription decision making processResponses were very similar amongst Ob/Gyns and PCPs,with rapidity of pain relief as the most important factor,minimization of sideeffects as the second most important factor,and cost/ease of reimbursement the third.The only notable point of differentiation between specialties was the ability to dose titrate,as 25%of Ob/Gyns thought it was the mostimportant factor(ranked 1 or 2)vs.10%of PCPsMost Important Factors in GnRH Antagonist Prescribing Decision Making Process(All respondents n=30)10Current and Future Prescribing Dynamics in EndometriosisSource:J.P.Morgan ResearchDirectional trends over a 3-year outlook support appreciable demand for all 3 GnRH-RA products,largely at the expense of OCPs;surgery/invasive procedures expected to maintain significant footholdPhysicians indicated the current and anticipated use of various treatment options for endometriosisPhysicianswereblindedto the GnRHantagonistnames,rathergivendrugsummariesto evaluate(AppendixB)Overall GnRH-RA product growth,led by Orilissa,expected to draw share primarily from OCPs and penetration of under-managedpatients(other/no therapy category)Despite being 2ndand 3rdto market entrants,physicians anticipate appreciable,immediate uptake of both relugolix and linzagolix at theirrespective approvals,but with Orilissa continuing to enjoying an overall first mover advantage.Current and Future Prescribing Dynamics for EM(All respondents n=30)Current and Future Prescribing Dynamics for Oral GnRH Antagonists(Ob/Gyns n=20;PCPs n=10)11Duration of GnRH Antagonist Therapy in EMSource:J.P.Morgan ResearchPhysician responses suggest 1-2+year GnRH-RA duration of therapy,descending with the degree of E2 suppression Based on clinical experience or familiarity with trial data,respondents indicated expected duration of GnRH-RA treatment in EMGnRH-RA regimens considered:lower-dose(partial E2 suppression)as a single agent,high-dose(full E2 suppression)with add-back therapy,orhigh-doseas a singleagent,Expectations indicate duration of therapy would typically last 1-2 years across the various optionsUnsurprisingly,low-dose/single agent and high-dose+ABT are likely to see longest duration-20-25%of patients for 2 yearsPhysician rationale for cessation of therapyMost commonly cited reason was side effects(including bone loss and vasomotor symptoms)or desire for pregnancy or surgery12Current Treatment Preference for Uterine FibroidsSource:J.P.Morgan ResearchWider variation in treatment patterns for uterine fibroids between specialties compared to endometriosisPhysicians were asked what percent of patients were managed with the following treatment optionsOralcontraceptives,opioidanalgesics,Lupron(or otherGnRHagonist),Orilissa,surgery,other,or no prescriptionmeds/NSAIDsGenerally,higher preference for invasive procedure among Ob/Gyns,and oral contraceptive use among PCPs.This pattern is not terriblysurprising,with PCP Ob/Gyn referrals for higher severity cases likely playing a factorNotably,some physicians currently indicate writing Orilissa Rx for UF management,with PCPs use(9%)trending ahead of Ob/Gyns(4%)All respondents(n=30)Ob/Gyns(n=20)PCPs(n=10)13Potential Role of GnRH Antagonists in the UF Treatment ParadigmSource:J.P.Morgan ResearchShort-term treatment(6 months)likely to predominate GnRH-RA use;however,results show strong support for long-term use,particularly among PCPs,in lieu of surgeryPhysicians were asked rate the likelihood of GnRH-RA treatment for different duration periodsImportantly,70%of respondents indicated plans to incorporate GnRH-RA use in their UF treatment practiceUnsurprisingly,responses overall favor shorter-term GnRH-RA use prior to surgery,in-line with current use of Lupron/agonist productsEncouragingly,a majority subscribe to the rationale for long-term GnRH-RA use as alternative to surgery,with higher preference amongPCPs(60-80%)than Ob/Gyns(40-65%)Short-term adjuvant GnRH-RA use post-surgery also finds appreciable support,particularly among Ob/Gyns(30-40%)Physician rationale for GnRH antagonist usePhysicians most frequently cited GnRH antagonist use to shrink fibroids/correct anemia in preparation for surgeryOthers cited long-term GnRH antagonist use as impractical in light of curative surgeryLong-term use may be reserved for patients who are not surgical candidatesFurther detail in Appendix D14Preferred GnRH Antagonist Profile for Uterine FibroidsSource:J.P.Morgan ResearchPatient preference anticipated to be roughly even between GnRH-RA strength options(full E2 suppression with ABT vs partial E2 suppression without)Can expect similar Orilissa/relugolix/linzagolix uptake in the treatment of uterine fibroids on the basis of each regimenPhysician commentary suggests that the decision will be patient dependent if ABT is warranted(Appendix E)Some physicians noted ABT could cause fibroid growthOthers will utilize ABT to prevent GnRH side effects15Preferred GnRH Antagonist Profile for Uterine Fibroids(Cont.)Source:J.P.Morgan ResearchBleeding cessation and pain relief take high priority in GnRH-RA regimen/product selection;DDI,titration and ABT convenience of lower concernsPhysicians rank ordered sevenmetrics(1=most important)as it relates to their GnRH antagonist prescription decision making processCessation of heavy menstrual bleeding was the most important factor,with rapidity of pain relief as the second,followed byminimization of side effects/cost and ease of reimbursementInterestingly,Ob/Gyns placed greater emphasis on access(cost/reimbursement)compared to PCPsMost Important Factors in GnRH-RA Prescribing Decision Making Process(All respondents n=30)16Payers Management and Outlook of OrilissaSource:J.P.Morgan ResearchEarly but encouraging days in the Orilissa formulary review process,with 75%coverage to dateWe surveyed25 payers on their review and outlook of Orilissa for the treatment of pain associated with endometriosis2/3 of payers have not completed formulary review25%have completed review and cover with prior authorization,while only 4%do not require prior authorization8%of overall payers(22%of completed reviews)do not cover OrilissaWe are expecting that management of GnRH-RA reimbursement will have moderate(55%)to tight(20%)restrictions over the next 3-5yearsNo payers expect loose/no restrictions,or very tight restrictions25%of payers were unsure about the future management of Orilissa formularyPayer review of Orilissa for Endometriosis Associated Pain(n=25)Anticipated Management of GnRHs on Formulary over next 3-5 years(n=25)17APPENDIXSource:J.P.Morgan Research18Appendix A:Orilissa SatisfactionSource:J.P.Morgan ResearchSpecialtyRating(1-6;6 very satisfied)CommentaryObstetrician/Gynecologist5Seems to work well based on limited experience to date,but still expensive.Obstetrician/Gynecologist5so far no issues its only been 3-4 months of useObstetrician/Gynecologist2too similar to lupronObstetrician/Gynecologist6Oral dosing and able