Endocrine KOLs are constructive on several new therapies for rare endocrine diseases, but reimbursement and long-term efficacy remain key to adoption.
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Endocrine KOLs are constructive on several new therapies for rare endocrine diseases, but reimbursement and long-term efficacy remain key to adoption.
Goldman Sachs lunch meeting notes show that physicians have had good experience with launched products such as Yorvipath, Crenessity, and Vykat, and believe there remains significant unmet need in indications such as PBH, PWS, CAH, and ACH.
- In hypoparathyroidism, Yorvipath is still viewed as the efficacy gold standard; weekly canvuparatide could win some patients on convenience if it can sustain roughly a 50% response rate.
- In CAH, Crenessity already has positive experience, but twice-daily dosing and limited androgen improvement are drawbacks; atumelnant's once-daily oral dosing and MC2R mechanism may be differentiated.
- In PBH, unmet need remains high; the KOL believes a 50% absolute reduction in Level 2/Level 3 hypoglycemic events would be clinically compelling, and avexitide could target the severe-patient segment.
- In PWS, doctors view setmelanotide's weight-loss data as unprecedented relative to existing therapies and place importance on hunger and quality-of-life endpoints; if reimbursement allows, combination use with Vykat is attractive.
- In ACH and acromegaly, dosing burden, fasting requirements, payer step edits, and insurance reimbursement remain important constraints on real-world adoption.
Report interpretation
Overview
This report summarizes Goldman Sachs' lunch discussion with adult endocrinologist Dr. Aren Skolnick. The doctor manages about 350 monthly patients across multiple endocrine areas, including hypoparathyroidism, congenital adrenal hyperplasia, post-bariatric hypoglycemia, Prader-Willi syndrome, hypothalamic obesity, achondroplasia, acromegaly, and Graves' disease/thyroid eye disease. Overall, the doctor is constructive on several newly launched or in-development therapies, but emphasizes that real-world adoption depends on efficacy completeness, dosing convenience, reimbursement, and patient quality of life.
Core views
The core view is that treatment for rare endocrine diseases is shifting from traditional symptomatic, high-burden therapies toward newer therapies that are more mechanistically differentiated, more convenient to administer, and better able to improve quality of life. Yorvipath still has a strong clinical position in hypoparathyroidism; Crenessity has value in CAH but is constrained by dosing frequency and androgen control; avexitide addresses a PBH population with substantial unmet need; setmelanotide's weight-loss and quality-of-life signal in PWS is highly regarded by the KOL; and oral or weekly therapies in ACH may expand treatment penetration.
Analysis framework
The report is primarily based on an interview with an in-house endocrine KOL, combined with the doctor's real-world patient volume, current prescribing experience, interpretation of candidate-drug clinical data, reimbursement observations, and treatment pathways across indications to assess the potential adoption space for the related products and development-stage assets.
Methodology notes
Assess drug adoption, unmet need, and data thresholds through interviews with clinical experts.
This framework is well suited to capturing real-world physician behavior and patient selection, but the sample size is limited, so conclusions should be validated alongside clinical trial data, reimbursement policy, and broader prescribing data.
Efficacy, dosing frequency, safety, quality of life, and payer access jointly determine adoption.
Physicians do not look at a single endpoint; instead, they consider response rate, event reduction, long-term durability, injection or oral convenience, fasting requirements, reimbursement difficulty, and manufacturer support as an integrated decision set.
Asset mapping & comparison
Structured mapping from thesis to named assets (strengths, weaknesses, peers, risks).
- ASND / YorvipathLaunched therapy for hypoparathyroidism, serving as the benchmark for canvuparatide.
- Strengths
- The KOL still views Yorvipath as the gold standard for efficacy, with around 80% efficacy over 26-52 weeks and stable results; patients can reduce supplements and maintain calcium levels.
- Weaknesses
- The daily injection frequency still leaves a convenience disadvantage, but patients who have already escalated therapy do not seem to mind it much.
- Comparison
- Compared with MBX's once-weekly canvuparatide, Yorvipath has the stronger efficacy benchmark; the weekly product needs convenience to offset its lower response rate.
- Risks
- If the weekly therapy can sustain long-term efficacy and reimbursement goes smoothly, it could divert some stable patients or new patients unwilling to inject daily.
- MBX / canvuparatideOnce-weekly development asset for hypoparathyroidism.
- Strengths
- Once-weekly convenience may attract patients stable on daily therapy who want fewer injections, and may also attract new patients who cannot tolerate daily injections.
- Weaknesses
- The 52-week response rate fell to 57%, below 79% at 26 weeks, so long-term efficacy durability still needs to be observed.
- Comparison
- The KOL believes that if weekly dosing can deliver about a 50% response rate, it would be an acceptable trade-off versus Yorvipath.
- Risks
- Further declines in response, payer barriers, or an overly rich pricing premium could limit adoption.
- NBIX / CrenessityLaunched CAH therapy, with related discussion of the PWS product Vykat.
- Strengths
- CAH patients can reduce glucocorticoid use and improve weight and glucose; reimbursement is generally manageable. Vykat improves patient and caregiver quality of life in PWS.
- Weaknesses
- Crenessity is dosed twice daily and mainly stabilizes rather than sharply lowers androgens; Vykat does not improve weight and requires monitoring for edema/hyperglycemia.
- Comparison
- In CAH it may face competition from CRNX atumelnant's once-daily oral dosing and mechanistic differentiation; in PWS, setmelanotide may be complementary on the weight dimension.
- Risks
- If competitors perform better on A4 reduction, dosing convenience, or quality-of-life endpoints, share could be affected.
- CRNX / atumelnant; PalsonifyCAH development asset and launched acromegaly product.
- Strengths
- Atumelnant offers once-daily oral dosing and an MC2R antagonism mechanism, with the potential to reduce A4 to below the upper limit of normal; Palsonify already has limited use and roughly half of acromegaly patients may qualify.
- Weaknesses
- Atumelnant still needs approval and more safety confirmation; Palsonify is constrained by high list price, payer step edits, competition from Mycapssa, and fasting requirements.
- Comparison
- Atumelnant's core differentiators versus Crenessity are dosing frequency and androgen control; Palsonify competes in acromegaly, where several effective therapies already exist.
- Risks
- Future LFT elevations above 3x ULN would raise safety concerns; Palsonify's fasting requirement may hurt adherence.
- AMLX / avexitidePotential therapy for PBH.
- Strengths
- PBH unmet need is high; at least 15%-20% of patients have regular severe hypoglycemic events, and a 50% absolute reduction in Level 2/Level 3 events would be clinically meaningful.
- Weaknesses
- Phase 3 data are still needed, and insurance coverage may require diagnostic documentation.
- Comparison
- Existing standards such as diazoxide are ineffective and carry a significant quality-of-life burden, and GLP-1 agonists are not especially effective either.
- Risks
- If efficacy falls short of the clinical hurdle, placebo response is high, or payer requirements are too strict, adoption may be slower than expected.
- RYTM / setmelanotide; ImcivreeTherapies related to PWS and hypothalamic obesity.
- Strengths
- The PWS data were described by the KOL as weight-loss results unprecedented relative to existing therapies, and HCV and other quality-of-life endpoints are attractive; in HO, the doctor plans to initiate treatment in about 20% of patients soon.
- Weaknesses
- In adult HO patients, GLP-1 reimbursement is relatively smooth and some patients can lose up to 15% of weight, creating real competition.
- Comparison
- In PWS, setmelanotide may complement Vykat, which improves quality of life but not weight.
- Risks
- If registrational studies cannot show both weight and quality-of-life benefits, or reimbursement does not support combination use, the commercial opportunity may be constrained.
- BBIO / infigratini; TYRA / dabogratinib; BMRN / Voxzogo; ASND / YuviwelAssets related to achondroplasia treatment.
- Strengths
- Oral drugs could significantly reduce the burden of daily pediatric injections; the once-weekly Yuviwel may also broaden treatment interest.
- Weaknesses
- Families may still be cautious about starting new drugs; FGFR-related hyperphosphatemia needs to be managed.
- Comparison
- Voxzogo is already being used in some patients, but the daily injection burden is substantial; the KOL believes dabogratinib, because of higher FGFR3 selectivity, could be comparable to or slightly better than infigratini in key studies.
- Risks
- Safety, long-term growth benefit, family acceptance, and reimbursement may all affect penetration.
- VRDN; ROIV/IMVTNames related to advanced therapies for Graves' disease/thyroid eye disease.
- Strengths
- The KOL notes that about 25% of Graves' disease patients are not well controlled on antithyroid drugs, and some additional patients are controlled but cannot discontinue ATDs, making them candidates for advanced therapies such as FcRn or IgG degradation agents.
- Weaknesses
- The report discusses this indication only briefly and provides no specific drug data or adoption volumes.
- Comparison
- Advanced therapies may be used long term or intermittently, similar to current ATD practice.
- Risks
- Efficacy, safety, dosing interval, and payer access still need further validation.
Key data
- Monthly patient volume managed by the KOLApproximately 350Covers multiple adult endocrine disease areas.
- Hypoparathyroidism patient countAbout 10, of whom 5 are on YorvipathPatients are generally satisfied because they can reduce supplements while maintaining calcium levels.
- canvuparatide response-rate thresholdAbout 50%The KOL认为 a weekly regimen with roughly a 50% response rate would be a reasonable trade-off; the 52-week response rate was 57%, versus 79% at 26 weeks.
- CAH patient countAbout 20, including 3 female patients using CrenessityUse has allowed glucocorticoid dose reduction, with improvements seen in weight and glucose.
- Crenessity reimbursement turnaroundUsually 3-4 weeksNBIX provides support with paperwork and prior authorization.
- PBH patient countAbout 30Roughly 40% are poorly controlled by diet or existing therapies, and at least 15%-20% have regular, severe hypoglycemic events.
- Initial addressable market estimate for PBHAbout 30,000 patients, versus 160,000 prevalent casesThe report says this estimate is broadly consistent with the severe, recurring-event population.
- avexitide efficacy threshold50% absolute reduction in Level 2/Level 3 eventsThe KOL believes this magnitude would be clinically compelling.
- Near-term treatable share of HO patientsAbout 20%The doctor plans to move some hypothalamic obesity patients into treatment based on weight, treatment refractoriness, and comorbidities.
- ACH patient count10 pediatric patients, including 2 on VoxzogoDaily injections are seen as a major burden in pediatric care.
- Potential additional treatment starts in ACHAbout 3 on infigratini, 3-4 on injectable therapyAn oral option could attract some families waiting for an oral drug launch.
- Number of acromegaly patientsAbout 20-25, including 2-3 on PalsonifyHigh pricing, step edits, and fasting requirements constrain early use.
Impact & implications
For investment implications, the report supports the view that rare endocrine disease still offers meaningful room for product innovation and commercialization, but the winning factors differ by asset: launched products need to prove durable real-world use and reimbursement progress, while development-stage assets need to establish clear differentiation in efficacy thresholds, quality-of-life endpoints, long-term data, and dosing convenience. Short- to medium-term catalysts for ASND, MBX, NBIX, CRNX, AMLX, RYTM, BBIO, BMRN, TYRA, VRDN, ROIV/IMVT, and other related names are more likely to come from data readouts, indication expansion, and physician-adoption feedback than from a simple market-size story.
Risks
- A single-KOL sample is limited and may not represent the broader physician population or regional differences.
- High-priced rare-disease therapies generally face insurance reimbursement, prior authorization, and payer step-edit barriers.
- Some development-stage assets still need key clinical data validation, and long-term efficacy durability and safety remain uncertain.
- Dosing frequency, fasting requirements, injection burden, and caregiver burden may materially affect real-world adherence.
- Safety monitoring such as LFT elevations, edema, hyperglycemia, and hyperphosphatemia may limit the eligible population.
- Some indications already have available therapies or substitutes, and insufficient differentiation could suppress the commercial opportunity.
What to watch
- Whether MBX canvuparatide's response rate in longer follow-up remains above the roughly 50% threshold the KOL considers acceptable.
- The magnitude of A4 reduction, the once-daily oral advantage, and LFT safety in future CRNX atumelnant data.
- Whether AMLX avexitide Phase 3 data can achieve roughly a 50% absolute reduction in Level 2/Level 3 hypoglycemic events.
- The priority and outcomes of weight, HCV/HCQT, and quality-of-life endpoints in RYTM setmelanotide's PWS registrational studies.
- Whether Vykat and setmelanotide obtain insurance support and form a combination-use scenario in PWS.
- Whether oral and once-weekly therapies for ACH can meaningfully broaden treatment willingness and reduce pediatric injection burden.
- Whether Palsonify can overcome step edits, fasting requirements, and competition from existing oral therapies in acromegaly.
- Real-world demand validation for advanced therapies in poorly controlled Graves' disease/thyroid eye disease patients or those unable to discontinue ATDs.