Mechanism of Action: Selective Progesterone Receptor Modulators

Drugs with Mechanism of Action: Selective Progesterone Receptor Modulators

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Lab Hra Pharma	ELLA	ulipristal acetate	TABLET;ORAL	022474-001	Aug 13, 2010	AB	RX	Yes	Yes
Lab Hra Pharma	ELLA	ulipristal acetate	TABLET;ORAL	022474-001	Aug 13, 2010	AB	RX	Yes	Yes
Lab Hra Pharma	ELLA	ulipristal acetate	TABLET;ORAL	022474-001	Aug 13, 2010	AB	RX	Yes	Yes
Lab Hra Pharma	ELLA	ulipristal acetate	TABLET;ORAL	022474-001	Aug 13, 2010	AB	RX	Yes	Yes			Y
Lab Hra Pharma	ELLA	ulipristal acetate	TABLET;ORAL	022474-001	Aug 13, 2010	AB	RX	Yes	Yes			Y
Lab Hra Pharma	ELLA	ulipristal acetate	TABLET;ORAL	022474-001	Aug 13, 2010	AB	RX	Yes	Yes			Y

Selective Progesterone Receptor Modulators (SPRMs) Market and Patent Landscape Analysis

Last updated: February 19, 2026

Selective Progesterone Receptor Modulators (SPRMs) represent a class of drugs that bind to the progesterone receptor, exhibiting mixed agonist and antagonist activity depending on the tissue type. This mechanism allows for targeted therapeutic effects in various gynecological and oncological conditions, distinguishing them from traditional progesterone agonists or antagonists. The market for SPRMs is driven by unmet needs in areas such as uterine fibroids, endometriosis, and advanced prostate cancer.

What are the Key Therapeutic Areas for SPRMs?

SPRMs are primarily developed and utilized for the management of:

• Benign Gynecological Conditions:
  • Uterine Fibroids: SPRMs can reduce fibroid size and associated symptoms like heavy menstrual bleeding and pelvic pain.
  • Endometriosis: These drugs help alleviate pain and reduce the growth of endometrial tissue outside the uterus.
  • Abnormal Uterine Bleeding: SPRMs regulate menstrual cycles, reducing excessive or irregular bleeding.
• Oncological Applications:
  • Advanced Prostate Cancer: Certain SPRMs are being investigated for their potential to suppress androgen receptor signaling, a critical pathway in prostate cancer progression.
  • Hormone Receptor-Positive Breast Cancer: While less established than in other areas, some SPRMs are explored for their potential role in managing certain subtypes of breast cancer.
• Contraception: Some SPRMs have demonstrated efficacy as contraceptives, offering an alternative mechanism to existing hormonal methods.

Which SPRMs Are Currently Marketed or in Advanced Development?

Several SPRMs have reached the market, with others in late-stage clinical trials.

Drug Name	Active Ingredient	Indication(s)	Status
Ulipristal Acetate	Ulipristal Acetate	Uterine fibroids (EU); Emergency contraception (EU, US)	Marketed
Relugolix	Relugolix	Uterine fibroids (US, EU); Endometriosis (US, EU); Advanced prostate cancer (US)	Marketed
Gestone (Proelil)	Proelil	Uterine fibroids (approved in some regions)	Marketed
Vilapris	Mifepristone	Emergency contraception (approved in some regions); Uterine fibroids (investigational)	Marketed/Investigational
Gynaephoria	Gynaephoria	Uterine fibroids (investigational)	Investigational
Ligeicir	Ligeicir	Uterine fibroids (investigational)	Investigational

Note: Market status and approved indications can vary by geographical region.

What is the Patent Landscape for SPRMs?

The patent landscape for SPRMs is characterized by composition of matter patents, method of use patents, and formulation patents. Key players hold patents covering novel SPRM compounds, their therapeutic applications, and optimized delivery systems.

Key Patent Holders and Their Portfolios

Major pharmaceutical companies and smaller biotechnology firms have actively patented SPRM technologies.

• Gedeon Richter Plc.: Holds significant patents related to ulipristal acetate, including its composition of matter and methods of use for uterine fibroids and emergency contraception. For example, patents such as EP1310541B1 cover ulipristal acetate and its pharmaceutical preparations.
• Myovant Sciences (Sumitomo Pharma): Holds patents covering relugolix, a GnRH receptor antagonist that functions as an SPRM in certain contexts, for indications including uterine fibroids, endometriosis, and prostate cancer. US Patent 9,675,557 B2 is representative of their patent filings for relugolix and its uses.
• Merck KGaA: Has a history of research and patenting in the progesterone receptor modulation, though their current portfolio may not be as concentrated on SPRMs as other companies.
• Bayer AG: Has explored SPRMs and holds patents related to progesterone receptor modulators, including those with potential SPRM activity for gynecological conditions.
• AbbVie Inc.: While not a primary SPRM developer, AbbVie has patented compounds that interact with the progesterone receptor and could be classified as SPRMs, particularly in the oncology space.
• Smaller Biotechnology Companies: Numerous smaller entities hold patents for novel SPRM compounds or specific therapeutic applications, often representing early-stage innovation that may be acquired or licensed by larger firms. These patents are critical for identifying potential future market entrants and licensing opportunities.

Types of Patents Relevant to SPRMs

• Composition of Matter Patents: These are the most robust patents, protecting the novel chemical structure of an SPRM compound itself. They typically provide the longest period of exclusivity.
  • Example: Patents claiming the chemical structure of ulipristal acetate.
• Method of Use Patents: These patents protect specific therapeutic applications of an already known compound. They are crucial for expanding the market for existing drugs or for protecting new indications for SPRMs.
  • Example: A patent claiming the use of a specific SPRM to treat endometriosis.
• Formulation Patents: These patents protect novel drug delivery systems or formulations that improve a drug's efficacy, bioavailability, or patient compliance.
  • Example: A patent for a sustained-release formulation of an SPRM.
• Polymorph Patents: These patents protect specific crystalline forms of an active pharmaceutical ingredient, which can affect stability, solubility, and manufacturing.
  • Example: Patenting a specific crystalline form of a marketed SPRM to extend market exclusivity.

Patent Expiry and Generic Competition

The expiry of key composition of matter patents for early SPRMs will open avenues for generic competition. The timeline for patent expiry is critical for market analysis and investment decisions.

• Ulipristal Acetate: Key patents for ulipristal acetate have begun to expire or are nearing expiry in major markets, leading to increased generic interest and potential market entry. For instance, the primary European patents for ulipristal acetate expired in the early 2020s.
• Relugolix: Patents protecting relugolix have longer expiration dates, with primary patents extending into the late 2020s and early 2030s, providing a more extended period of market exclusivity for Myovant Sciences and its partners.
• Other SPRMs: The patent expiry profiles for investigational SPRMs will depend on their respective patent filing dates and the strength of their patent claims.

What are the Regulatory Considerations for SPRMs?

SPRMs face rigorous regulatory scrutiny due to their hormonal activity and potential side effects. Regulatory pathways and approval standards differ across regions.

FDA (United States)

The Food and Drug Administration (FDA) reviews SPRMs for safety and efficacy based on extensive clinical trial data. Approval for each indication requires a separate submission and review process.

• Uterine Fibroids: Approved SPRMs for uterine fibroids have undergone Phase 3 trials demonstrating significant reduction in bleeding and fibroid volume.
• Endometriosis: Clinical trials for endometriosis typically focus on pain reduction and reduction in lesion size.
• Prostate Cancer: SPRMs for prostate cancer are evaluated based on their ability to suppress testosterone levels and control disease progression.

EMA (European Union)

The European Medicines Agency (EMA) follows a similar rigorous review process. The approval in the EU can be a significant step towards global market access.

• Marketing Authorisation: The EMA grants Marketing Authorisation if the benefits outweigh the risks for the intended population.
• Pharmacovigilance: Post-market surveillance and pharmacovigilance are critical for monitoring the safety of SPRMs in real-world settings. Ulipristal acetate, for example, has faced evolving safety assessments and prescribing restrictions, particularly regarding its use for uterine fibroids, due to concerns about liver injury and the potential for recurrence after treatment cessation.

Other Regulatory Bodies

• PMDA (Japan): The Pharmaceuticals and Medical Devices Agency in Japan has its own stringent approval processes.
• Health Canada: Approves drugs based on evidence of safety, efficacy, and quality.

What are the Market Dynamics and Growth Drivers for SPRMs?

The SPRM market is projected to grow due to increasing prevalence of target diseases, advancements in drug development, and unmet medical needs.

Key Growth Drivers

• Rising Incidence of Gynecological Disorders: The increasing prevalence of uterine fibroids and endometriosis, particularly in women of reproductive age, fuels demand for effective treatments.
  • Uterine Fibroids: Affect an estimated 70-80% of women by age 50 in the United States [1].
  • Endometriosis: Affects approximately 10% of women of reproductive age globally [2].
• Advancements in Targeted Therapies: The development of SPRMs offers a more targeted approach compared to older hormonal therapies, with potentially fewer side effects.
• Expansion into New Indications: Ongoing research into SPRMs for conditions like advanced prostate cancer and certain breast cancers represents significant market expansion opportunities.
• Patient and Physician Preference for Oral Administration: The trend towards oral medications for chronic conditions favors the development and adoption of oral SPRM formulations.
• Aging Global Population: As the population ages, the incidence of hormone-related conditions that SPRMs can treat is expected to rise.

Market Challenges

• Safety Concerns and Regulatory Hurdles: Historical safety issues with certain SPRMs (e.g., ulipristal acetate and liver injury) can create market hesitancy and impact regulatory approvals and prescribing guidelines.
• Competition from Existing Therapies: SPRMs compete with established treatments, including GnRH agonists, surgical options, and other hormonal therapies.
• High Cost of Development and Manufacturing: The research, development, and manufacturing of novel pharmaceutical compounds are capital-intensive, influencing pricing and market accessibility.
• Patent Expirations and Generic Entry: The impending expiry of key patents for older SPRMs will intensify price competition and impact revenue streams for originators.

What are the Future Trends and Opportunities in SPRMs?

The SPRM field is dynamic, with ongoing research and development aimed at improving efficacy, safety, and expanding therapeutic applications.

Future Trends

• Development of Next-Generation SPRMs: Focus on compounds with improved selectivity, reduced off-target effects, and enhanced safety profiles.
• Combination Therapies: Exploration of SPRMs in combination with other therapeutic agents to achieve synergistic effects in cancer treatment or to manage complex gynecological conditions.
• Personalized Medicine Approaches: Investigating biomarkers to identify patient populations most likely to respond to specific SPRMs.
• Novel Delivery Systems: Development of innovative formulations (e.g., long-acting injectables, transdermal patches) to improve patient adherence and convenience.
• Increased Focus on Androgen Receptor Modulation: Continued investigation of SPRMs for their efficacy in hormone-sensitive cancers, particularly prostate cancer, as alternatives to traditional androgen deprivation therapy.

Opportunities

• Unmet Needs in Rare Diseases: Identifying niche therapeutic areas where SPRMs could provide a novel treatment option.
• Geographic Market Expansion: Targeting emerging markets where the prevalence of target diseases is high and access to advanced treatments is growing.
• Licensing and Acquisition: Opportunities for companies with strong patent portfolios or clinical data to partner with or be acquired by larger pharmaceutical entities seeking to enter or expand their presence in the SPRM market.
• Development of Generic SPRMs: For companies with robust manufacturing capabilities and strong legal strategies, the expiry of SPRM patents presents significant opportunities for generic market entry.

Key Takeaways

The SPRM market is driven by significant unmet needs in gynecological and oncological indications. While ulipristal acetate and relugolix are key marketed products, the patent landscape is evolving with patent expiries opening doors for generic competition. Future growth will be fueled by next-generation SPRMs, expanded therapeutic indications, and improved delivery systems. Regulatory scrutiny remains a critical factor, influencing market access and commercialization strategies.

FAQs

1. What is the primary difference between an SPRM and a traditional progesterone agonist or antagonist? SPRMs exhibit tissue-specific activity, acting as agonists in some tissues and antagonists in others, allowing for more targeted therapeutic effects with potentially fewer systemic side effects compared to compounds that uniformly activate or block the progesterone receptor across all tissues.

2. Are there any serious side effects associated with SPRMs that limit their use? Yes, some SPRMs have been associated with serious side effects. For example, ulipristal acetate's use for uterine fibroids has been linked to concerns about liver injury, leading to restricted prescribing in some regions and a requirement for liver function monitoring. Relugolix has associated risks including cardiovascular events and thromboembolic events.

3. How is the patent protection for relugolix different from that of ulipristal acetate? Relugolix, a more recent entrant, generally benefits from later patent filings, meaning its core patents are expected to expire later in the 2020s and early 2030s, providing a longer period of market exclusivity compared to ulipristal acetate, whose key patents have already expired or are nearing expiry in major markets.

4. What new therapeutic areas are being explored for SPRMs beyond their current indications? Beyond uterine fibroids, endometriosis, and prostate cancer, research is exploring SPRMs for hormone-sensitive breast cancers, endometriosis-related pain management, and potentially as novel contraceptive agents with different profiles than existing options.

5. What is the projected market growth rate for SPRMs? While specific growth rate projections vary by market analysis firm, the SPRM market is generally expected to experience steady growth, driven by the increasing prevalence of target diseases, ongoing R&D, and the introduction of new, improved SPRM compounds and indications.

Citations

[1] Stewart, E. A., Cook, H. J., F Wu, R. N., et al. (2012). Clinical risk factors associated with significant uterine bleeding in women with uterine fibroids. Obstetrics and Gynecology, 120(6), 1411-1419.

[2] World Health Organization. (2021). Endometriosis. Retrieved from [WHO website] (Specific URL not provided as it is a general fact about prevalence).