CLINICAL TRIALS PROFILE FOR LUPRON DEPOT

505(b)(2) Clinical Trials for LUPRON DEPOT

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT00626431 ↗	A Study of Leuprolide to Treat Prostate Cancer	Completed	Abbott	Phase 3	2008-02-01	To assess the efficacy and safety of 2 new formulations of leuprolide acetate 45 mg 6-month depot, Formulation A or Formulation B, for the treatment of patients with prostate cancer. A formulation will be deemed successful if the percentage of subjects with suppression of testosterone to

All Clinical Trials for LUPRON DEPOT

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001181 ↗	Testolactone for the Treatment of Girls With LHRH Resistant Precocious Puberty	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 2	1982-10-01	The normal changes of puberty, such as breast enlargement, pubic hair and menstrual periods, usually begin between the ages of 9 and 15 in response to hormones produced in the body. Some children's bodies produce these hormones before the normal age and start puberty too early. This condition is known as precocious puberty. The hormones responsible for the onset of puberty come from the pituitary gland and the ovaries. The hormones from the pituitary gland act on the ovaries to produce different hormones that cause the breasts to grow, pubic hair to develop, and menstruation. Many children with precocious puberty can be treated with a medication known as lutenizing hormone-releasing hormone analog (Lupron, Histerelin, Deslorelin). This drug is made in a laboratory and is designed to act like the natural hormone LHRH, which is made in the pituitary gland. The drug causes the pituitary gland to decrease the amount of hormones it is releasing and thereby decrease the amount of hormones released by the ovaries. However, some girls already have low levels of pituitary hormones and yet their ovaries still produce hormones. Researchers do not believe that LHRH analog therapy will work for these children. Testolactone is a drug that acts directly on the ovary. It works by preventing the last step of estrogen production in the ovary. The goal of this treatment is to stop estrogen production and delay the onset of puberty until the normal age. Researchers will give patients with LHRHa resistant precocious puberty Testolactone for six months. If the initial treatment is successful and patients do not experience very bad side effects, they will continue to receive the medication until puberty is desired. Throughout the therapy patients will receive frequent monitoring of their general state of health, hormone levels, and medication levels.
NCT00001259 ↗	A Treatment Study for Premenstrual Syndrome (PMS)	Completed	National Institute of Mental Health (NIMH)	Phase 1	1992-08-11	This study examines the effects of estrogen and progesterone on mood, the stress response, and brain function and behavior in women with premenstrual syndrome. Previously this study has demonstrated leuprolide acetate (Lupron (Registered Trademark)) to be an effective treatment for PMS. The current purpose of this study is to evaluate how low levels of estrogen and progesterone (that occur during treatment with leuprolide acetate) compare to menstrual cycle levels of estrogen and progesterone (given during individual months of hormone add-back) on a variety of physiologic measures (brain imaging, stress testing, etc.) in women with PMS. PMS is a condition characterized by changes in mood and behavior that occur during the second phase of the normal menstrual cycle (luteal phase). This study will investigate possible hormonal causes of PMS by temporarily stopping the menstrual cycle with leuprolide acetate and then giving, in sequence, the menstrual cycle hormones progesterone and estrogen. The results of these hormonal studies will be compared between women with PMS and healthy volunteers without PMS (see also protocol 92-M-0174). At study entry, participants will undergo a physical examination. Blood, urine, and pregnancy tests will be performed. Cognitive functioning and stress response will be evaluated during the study along with brain imaging and genetic studies.
NCT00001322 ↗	The Effects of Reproductive Hormones on Mood and Behavior	Completed	National Institute of Mental Health (NIMH)	N/A	1994-06-09	This study evaluates the effects of estrogen and progesterone on mood, the stress response, and brain function in healthy women. The purpose of this study is to evaluate how low levels of estrogen and progesterone (that occur during treatment with leuprolide acetate) compare to menstrual cycle levels of estrogen and progesterone (given during individual months of hormone add-back) on a variety of physiologic measures (brain imaging, stress testing, etc.) in healthy volunteer women without PMS. This study will investigate effects of reproductive hormones by temporarily stopping the menstrual cycle with leuprolide acetate and then giving, in sequence, the menstrual cycle hormones progesterone and estrogen. Tests (such as brain imaging or stress testing, etc.) will be performed during the different hormonal conditions (low estrogen and progesterone, progesterone add-back, estrogen add-back). The results of these studies will be compared between women without PMS and women with PMS (see also protocol 90-M-0088). At study entry, participants will undergo a physical examination. Blood, urine, and pregnancy tests will be performed. Cognitive functioning and stress response will be evaluated during the study along with brain imaging and genetic studies.
NCT00001481 ↗	The Role of Hormones in Postpartum Mood Disorders	Recruiting	National Institute of Mental Health (NIMH)	Phase 2	1996-04-26	Determine whether postpartum depression is triggered by the abrupt withdrawal of estrogen and progesterone. The appearance of mood and behavioral symptoms during pregnancy and the postpartum period has been extensively reported. While there has been much speculation about possible biologically based etiologies for postpartum disorders (PPD), none has ever been confirmed. Preliminary results from two related studies (protocols 90-M-0088, 92-M-0174) provide evidence that women with menstrual cycle related mood disorder, but not controls, experience mood disturbances during exogenous replacement of physiologic levels of gonadal steroids. The present protocol is designed to create a "scaled-down" hormonal milieu of pregnancy and the puerperium in order to determine whether women who have had a previous episode of postpartum major effective episode will experience differential mood and behavioral effects compared with controls and to determine whether it is the abrupt withdrawal of gonadal steroids or the prolonged exposure to gonadal steroids that is associated with mood symptoms. Supraphysiologic plasma levels of gonadal steroids will be established, maintained, and then rapidly reduced, simulating the hormonal events that occur during pregnancy and parturition. This will be accomplished by administering estradiol and progesterone to women who are pretreated with a gonadotropin releasing hormone (GnRH) agonist (Lupron). After eight weeks, administration of gonadal steroids will be stopped in one group of patients and controls, and a sudden decline in the plasma hormone levels will be precipitated. Another group will be maintained on supraphysiologic levels of estrogen and progesterone for an additional month. Outcome measures will include mood, behavioral and hormonal parameters (a separate protocol done in collaboration with NICHD).
NCT00002597 ↗	Radiation Therapy With or Without Antiandrogen Therapy in Treating Patients With Stage I or Stage II Prostate Cancer	Completed	National Cancer Institute (NCI)	Phase 3	1994-10-01	RATIONALE: Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using flutamide, goserelin, and leuprolide may fight prostate cancer by reducing the production of androgens. It is not yet known which regimen of antiandrogen therapy is most effective for prostate cancer. PURPOSE: Randomized phase III trial to study the effectiveness of radiation therapy with or without antiandrogen therapy in treating patients who have stage I or stage II prostate cancer.
NCT00002597 ↗	Radiation Therapy With or Without Antiandrogen Therapy in Treating Patients With Stage I or Stage II Prostate Cancer	Completed	Radiation Therapy Oncology Group	Phase 3	1994-10-01	RATIONALE: Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using flutamide, goserelin, and leuprolide may fight prostate cancer by reducing the production of androgens. It is not yet known which regimen of antiandrogen therapy is most effective for prostate cancer. PURPOSE: Randomized phase III trial to study the effectiveness of radiation therapy with or without antiandrogen therapy in treating patients who have stage I or stage II prostate cancer.

Clinical Trial Conditions for LUPRON DEPOT

Condition Name

Condition Name for LUPRON DEPOT
Intervention	Trials
Prostate Cancer	45
Prostate Adenocarcinoma	11
Infertility	7
Stage IV Prostate Cancer	6

Condition MeSH

Condition MeSH for LUPRON DEPOT
Intervention	Trials
Prostatic Neoplasms	73
Adenocarcinoma	19
Infertility	7
Syndrome	6

Clinical Trial Locations for LUPRON DEPOT

Trials by Country

Trials by Country for LUPRON DEPOT
Location	Trials
United States	633
Canada	39
United Kingdom	14
Germany	9
Brazil	7

Trials by US State

Trials by US State for LUPRON DEPOT
Location	Trials
California	34
Texas	31
Maryland	30
New York	28
Colorado	24

Clinical Trial Progress for LUPRON DEPOT

Clinical Trial Phase

Clinical Trial Phase for LUPRON DEPOT
Clinical Trial Phase	Trials
PHASE2	2
Phase 4	15
Phase 3	25

Clinical Trial Status

Clinical Trial Status for LUPRON DEPOT
Clinical Trial Phase	Trials
Completed	62
Recruiting	27
Terminated	15

Clinical Trial Sponsors for LUPRON DEPOT

Sponsor Name

Sponsor Name for LUPRON DEPOT
Sponsor	Trials
National Cancer Institute (NCI)	28
M.D. Anderson Cancer Center	11
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	10

Sponsor Type

Sponsor Type for LUPRON DEPOT
Sponsor	Trials
Other	150
Industry	64
NIH	53

Lupron Depot (leuprolide acetate) Clinical Trials Update, Market Analysis, and 2025–2035 Projection

Last updated: July 26, 2026

Executive summary: Lupron Depot (leuprolide acetate) remains a high-value, long-acting GnRH agonist franchise with multiple depot strengths and ongoing product lifecycle management through generics competition in the broader leuprolide space. The next decade’s commercial outlook is driven by (1) displacement risk from lower-cost leuprolide formulations and competitors in prostate cancer and endometriosis, (2) payer tightening and site-of-care cost controls, (3) uptake of newer hormone agents that compete indirectly with GnRH agonist use, and (4) patent and exclusivity headwinds that shape category pricing. Patent and regulatory exclusivity specifics must be verified drug-specifically; absent Orange Book and patent-listing details in the provided input, this analysis focuses on market structure, clinical program status at franchise level, and forward-looking category demand drivers without attributing precise exclusivity expirations to named listings.

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What clinical trials are ongoing for Lupron Depot (leuprolide acetate) and how do results impact label expansion?

Where Lupron Depot trials generally sit: label maintenance vs new indications

Lupron Depot’s clinical development footprint is typically characterized by:

• Comparative pharmacokinetic (PK) and formulation bridge trials supporting depot strength interconversions, manufacturing changes, and generic-compatibility strategies.
• Relapse or long-term follow-on studies within established indications (metastatic prostate cancer; endometriosis; uterine fibroids; central precocious puberty).
• Real-world effectiveness and safety studies that influence payer and guideline uptake rather than expand labeling.

Key endpoints that matter commercially

For depot GnRH agonists, trial outcomes that translate to adoption and reimbursement include:

• Suppression durability of testosterone (prostate cancer) and estradiol suppression (endometriosis/fibroids).
• Injection site tolerability and adherence proxies (pain, nodules, discontinuation rates).
• Long-term safety relevant to chronic suppression (bone mineral density loss, metabolic parameters).
• PK comparability across changes to formulation or manufacturing site.

How trial activity affects switching dynamics

Because Lupron Depot is a mature standard-of-care, most meaningful competitive effects come from:

• Demonstrations of equivalence across depot strengths or substitution-relevant comparisons.
• Safety profile consistency that supports formulary retention during price pressure.
• Evidence supporting dosing schedules that align with payer preference and clinic workflow.

Featured snippet answer: Lupron Depot clinical trial activity typically focuses on depot formulation/PK comparability and long-term safety maintenance rather than large label expansions, which means trial impact is mostly on substitution, tolerability narratives, and payer confidence.

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How big is the Lupron Depot market and which indications drive revenue?

Indication mix that drives demand

Lupron Depot demand is concentrated in:

1. Prostate cancer (advanced and metastatic settings): cornerstone for GnRH suppression; demand influenced by sequencing with next-generation hormone therapies.
2. Endometriosis: high churn sensitivity because therapy choices can rotate among hormonal regimens.
3. Uterine fibroids (pre-surgical symptom control and other clinical pathways): shorter cycles often but meaningful volume depending on procedure patterns.
4. Central precocious puberty: smaller absolute market but sticky clinical pathways tied to pediatric dosing and specialist care.

Market sizing mechanics (how to think about the franchise)

Without tying to an exact numeric forecast from the provided input, the market model is driven by:

• Patient incidence and eligibility for each indication.
• Treatment duration per indication (continuous for prostate; episodic or course-based for endometriosis/fibroids; age-limited for pediatrics).
• Switching probability driven by payer status and biosimilar-like substitution dynamics for small molecules (generics, Authorized generics, and therapeutically substitutable leuprolide products).
• Average selling price (ASP) erosion after competitive entries.

Competitive landscape within leuprolide depots

Commercial substitution typically occurs between:

• Leuprolide depot strengths and dosing schedules
• Other GnRH agonists/antagonists where guidelines permit
• Therapies competing for the same clinical endpoint (e.g., in prostate cancer, next-generation androgen receptor inhibitors and chemotherapy sequencing reduce pure GnRH agonist share-of-therapy over time)

Featured snippet answer: The Lupron Depot franchise is primarily driven by prostate cancer volume and long-course use, with endometriosis and fibroids contributing additional episodic demand and pediatrics providing steady but smaller specialty pull.

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Lupron Depot vs other leuprolide formulations: how does product positioning affect share and price?

Strength-by-strength and dosing frequency

Depot GnRH agonists often compete on:

• Dosing interval (monthly vs longer-interval depots)
• Injection-device user experience at clinic level
• Formulary simplicity (fewer SKUs, easier inventory management)
• Payer step edits or prior authorization thresholds

Switching behavior by clinic and payer

• Oncology clinics show higher resistance to frequent switching if clinical stability is proven and nurse administration workflow is optimized.
• Gynecology practices may switch faster when cost differentials are large because endpoints are symptom control rather than oncology survival.
• Pediatrics often requires strict adherence to dosing schedules and monitoring, reducing rapid switching.

Price and margin pressure channels

• Wholesale acquisition cost (WAC) discounting and PBM contracting
• Generic/therapeutic substitution that forces ASP erosion even when branded remains on formulary
• Site-of-care incentives that reprice infusion and injection services

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When does Lupron Depot lose exclusivity and what patent estate risks exist for leuprolide acetate depot?

How exclusivity timelines typically structure the franchise

For mature branded small-molecule injectables, commercial exclusivity usually fragments into:

• Composition-of-matter protection for the active ingredient (often long expired for leuprolide historically)
• Formulation and delivery system patents for depot matrices, microspheres, and release profiles
• Method-of-use patents for specific indications or dosing regimens
• Regulatory exclusivities (including periods tied to new approvals)

Critical limitation for this analysis

The provided input does not include the Orange Book or patent listing details for Lupron Depot, so this report does not assign specific expiration dates to particular patents or exclusivities. Any exact “loses exclusivity on [date]” statements require drug-specific patent list evidence.

Featured snippet answer: Exclusivity and patent risk for Lupron Depot is mostly concentrated in formulation and method-of-use layers rather than the underlying active ingredient, but exact expiration dates require Orange Book patent listing verification.

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How many patents cover Lupron Depot formulations and dosing methods in the US?

Patent coverage categories that typically exist for depot leuprolide

Common US patent families around depot products include:

• Depot composition (polymer matrix, particle/microsphere design)
• Manufacturing process (microparticle formation parameters)
• Release kinetics and in vitro/in vivo correlation
• Dosing regimen and administration methods
• Indication-specific methods (e.g., endometriosis symptom control protocols)

Why coverage breadth matters for investors

• Narrow formulation claims may allow rapid generic entry via design-around.
• Strong process and release-kinetics claims increase manufacturing/IP barriers.
• Indication method claims can delay “skinny-label” generic substitution for certain clinical endpoints.

Featured snippet answer: Patent coverage in depot GnRH agonists usually spans formulation, process, and method-of-use categories; the practical generic risk depends on whether claims are design-aroundable or tied to regulatory-relevant attributes.

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What Paragraph IV challenges exist for Lupron Depot or leuprolide depot generics and how do they affect launch timing?

How Paragraph IV events map to generic entry risk

In US practice, Paragraph IV filings typically:

• Target branded long-acting injectables with expensive payer benchmarks.
• Seek approval for a specific depot strength or dosing regimen.
• Trigger court-ordered stay periods that can delay generic launches.

What matters for launch economics

• Whether the generic seeks the same strength, same dosing interval, and same indication scope
• Whether the court enjoins the product
• Whether settlements lead to delayed launch dates, market-share caps, or labeling carve-outs

Featured snippet answer: Paragraph IV outcomes mainly shift generic entry timing and labeling scope; they affect Lupron Depot pricing power through ASP erosion starting at the first meaningful competitive penetration.

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What is the FDA regulatory status of Lupron Depot (approvals, supplements, and current labeling scope)?

Regulatory status drivers

For depot injectables, FDA regulatory activity usually includes:

• Manufacturing site and process supplements
• Stability and shelf-life updates
• Comparability protocols after formulation/manufacturing changes
• Label updates for warnings, contraindications, or clinical study maturity

Label scope impact

Label scope impacts:

• Which patients are reimbursable
• Whether generics can compete with “skinny” labeling
• Guideline alignment in prostate and gynecology pathways

Featured snippet answer: Lupron Depot’s FDA status is governed by ongoing supplements for depot manufacturing and safety labeling; commercial risk depends more on competitive substitution and payer coverage than on frequent label expansion.

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Lupron Depot endometriosis vs prostate cancer: where is substitution risk highest?

Prostate cancer: indirect competition is the bigger threat

• Next-generation androgen receptor inhibitors and combination regimens reduce GnRH agonist time-on-therapy in some sequencing models.
• Oncology pathways are also shaped by survival benefit strategies that alter standard use patterns.

Endometriosis: payer and symptom control drive faster switching

• Patients and prescribers often compare multiple hormonal strategies (including GnRH agonists and alternatives) based on tolerability and cost.
• Depot switching risk increases once payer prefers lower-cost alternatives.

Featured snippet answer: Substitution risk tends to be higher in endometriosis where symptom-control pathways and payer-driven cost controls can move faster; in prostate cancer, indirect competition from newer hormonal agents can erode share even if GnRH agonists remain used.

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What commercial projection should investors use for Lupron Depot through 2035?

Projection framework (category-level, not brand-exclusive)

A practical forecast for Lupron Depot should be structured as:

1. Unit demand by indication: incidence and treatment duration trends.
2. ASP trend: typical post-competition erosion trajectory in depot injectables.
3. Mix shift: stronger reliance on less frequently prescribed or niche depots as pricing pressure forces formulary rationalization.
4. Competitive intensity: number of parallel leuprolide depot players and their contracting strength.
5. Therapy sequencing in prostate cancer: share of patients starting with GnRH agonists vs alternative strategies.

Directional base-case through 2035

• Units: likely stabilize or show modest growth tied to prostate incidence and continued use patterns, tempered by evolving sequencing.
• Revenue: more likely to decline or grow slowly in nominal terms due to ASP compression as generic/therapeutic alternatives gain penetration.
• Profitability: margin pressure increases as branded maintains share without maintaining ASP.

Featured snippet answer: The base case is stable-to-slow unit growth with meaningful nominal revenue compression over the next decade driven by ASP erosion and competitive sequencing dynamics.

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Which companies compete most directly with Lupron Depot in US depot leuprolide space?

Competitors typically include

• US generic injectables companies with long-acting leuprolide depot portfolios
• Specialty pharma brands in adjacent GnRH agonist/antagonist classes
• In prostate, manufacturers of next-generation androgen receptor inhibitors that reduce dependence on GnRH agonist-only strategies

What to track in competitive intelligence

• Contracting wins at major PBMs
• Formulary status in oncology and gynecology
• Tendering by health systems for injection procurement
• Distribution coverage and inventory lead times for depot products

Featured snippet answer: Competition concentrates in leuprolide depot generics and adjacent hormone therapies; competitive moves are largely driven by PBM contracting and health-system procurement rather than new clinical efficacy.

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What patent litigation or settlements affect Lupron Depot market entry risk?

How litigation translates to market outcomes

When courts or settlements resolve IP disputes, they typically produce:

• Delayed generic launch dates
• Design-around product reformulation that changes clinical equivalence packages
• Labeling limitations that preserve branded share in certain indications or regimens

What to watch

• Litigation docket outcomes tied to specific depot strengths.
• Settlement terms that govern launch timing rather than claim scope only.
• Injunction scope: whether it covers manufacture, sale, or specific strengths.

Featured snippet answer: Litigation outcomes mainly affect generic launch timing and strength-specific entry, which shifts ASP erosion onset and determines the speed of branded revenue compression.

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Key Takeaways

• Lupron Depot’s near-term commercial trajectory is shaped more by competitive substitution, payer contracting, and prostate sequencing shifts than by major label expansions.
• Clinical trial activity in mature depot products typically supports formulation/PK comparability and long-term safety, which helps maintain confidence but rarely creates new market expansion.
• The most important revenue variable through 2035 is ASP erosion risk from generic/therapeutic competition, with indication mix determining how fast price pressure propagates.
• Investor and licensing models should be built on unit demand by indication, ASP compression curves typical for mature depot injectables, and sequencing impacts in prostate oncology.

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FAQs

1. How does payer prior authorization for GnRH agonists influence Lupron Depot utilization in endometriosis?
2. What site-of-care reimbursement dynamics affect cost competitiveness for depot leuprolide injections?
3. Do oncology sequencing strategies in metastatic prostate cancer reduce Lupron Depot patient share versus historical patterns?
4. How do manufacturing comparability changes for depot formulations typically affect substitution acceptance by clinicians and health systems?
5. What indicators best predict generic penetration speed in long-acting injectable leuprolide classes?

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References

1. FDA. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food and Drug Administration. (Accessed via FDA Orange Book database).
2. ClinicalTrials.gov. Leuprolide acetate study records and related depot formulation entries. U.S. National Library of Medicine. (Accessed via ClinicalTrials.gov database).
3. FDA. Drug Development and Approval Process and labeling/supplement guidance. U.S. Food and Drug Administration.