PROPULSID Drug Patent Profile

Which patents cover Propulsid, and what generic alternatives are available?

Propulsid is a drug marketed by Janssen Pharms and Janssen Pharma and is included in three NDAs.

The generic ingredient in PROPULSID is cisapride monohydrate. There are two drug master file entries for this compound. Additional details are available on the cisapride monohydrate profile page.

Summary for PROPULSID

US Patents:	0
Applicants:	2
NDAs:	3
Raw Ingredient (Bulk) Api Vendors:	42
Clinical Trials:	1
Patent Applications:	3,589
DailyMed Link:	PROPULSID at DailyMed

Recent Clinical Trials for PROPULSID

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Temple University	N/A
American College of Gastroenterology	N/A

See all PROPULSID clinical trials

US Patents and Regulatory Information for PROPULSID

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Janssen Pharms	PROPULSID	cisapride monohydrate	SUSPENSION;ORAL	020398-001	Sep 15, 1995		DISCN	No	No
Janssen Pharma	PROPULSID QUICKSOLV	cisapride monohydrate	TABLET, ORALLY DISINTEGRATING;ORAL	020767-001	Nov 7, 1997		DISCN	No	No
Janssen Pharms	PROPULSID	cisapride monohydrate	TABLET;ORAL	020210-001	Jul 29, 1993		DISCN	No	No
Janssen Pharms	PROPULSID	cisapride monohydrate	TABLET;ORAL	020210-002	Dec 23, 1993		DISCN	No	No

Expired US Patents for PROPULSID

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Janssen Pharms	PROPULSID	cisapride monohydrate	SUSPENSION;ORAL	020398-001	Sep 15, 1995
Janssen Pharms	PROPULSID	cisapride monohydrate	TABLET;ORAL	020210-002	Dec 23, 1993
Janssen Pharms	PROPULSID	cisapride monohydrate	TABLET;ORAL	020210-001	Jul 29, 1993

International Patents for PROPULSID

See the table below for patents covering PROPULSID around the world.

Country	Patent Number	Title	Estimated Expiration
European Patent Office	0076530	NOVEL N-(3-HYDROXY-4-PIPERIDINYL)BENZAMIDE DERIVATIVES
Denmark	435182
Bosnia and Herzegovina	96068
Spain	8603413	"PROCEDIMIENTO PARA LA OBTENCION DE LA CIS-4-AMINO-5-CLORO-2-METO-XI-N-(1-(3-(4-FLUOROFENOXI)PROPIL)-3-METOXI-4-PIPERI- DIL)BENZAMIDA" (Piperidyl-benzamide deriv. - for use in synthesis of pharmacological prods. Piperidyl-benzamide deriv.)
Hong Kong	81188	NOVEL N-(3-HYDROXY-4-PIPERIDINYL)BENZAMIDE DERIVATIVES
U.S.S.R.	1593569	CПOCOБ ПOЛУЧEHИЯ ПPOИЗBOДHЫX N-(3-ГИДPOKCИ-4-ПИПEPИДИHИЛ)БEHЗAMИДA ИЛИ ИX KИCЛOTHO-AДДИTИBHЫX COЛEЙ (METHOD OF PRODUCING DERIVATIVES OF N-(3-HYDROXY-4-PYPYRIDINYL) BENZAMIDE OR THEIR ACID-ADDITIVE SALTS)

Supplementary Protection Certificates for PROPULSID

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
0076530	SPC/GB93/037	United Kingdom

PROPULSID Market Analysis and Financial Projection Experimental

Market Dynamics and Financial Trajectory for the Drug: PROPULSID (Cisapride)

Introduction

PROPULSID, known generically as cisapride, was a prokinetic agent used to treat gastrointestinal disorders such as gastroesophageal reflux disease (GERD) and other conditions involving delayed gastric emptying. The drug's market dynamics and financial trajectory were significantly influenced by its safety profile, regulatory actions, and subsequent market withdrawal.

Development and Initial Market Success

Cisapride was developed and marketed by Janssen Pharmaceutica, a subsidiary of Johnson & Johnson. It was approved by the FDA in 1993 and quickly gained popularity due to its effectiveness in treating various gastrointestinal conditions. The drug's initial success was driven by its unique mechanism of action, which enhanced gastrointestinal motility without significantly affecting gastric secretions[4].

Safety Concerns and Regulatory Actions

Despite its initial success, cisapride faced significant safety concerns. Post-marketing surveillance revealed serious cardiac side effects, including QT interval prolongation and torsades de pointes, which could lead to life-threatening arrhythmias. These findings prompted regulatory actions, including warnings and eventual restrictions on its use.

FDA Warnings and Restrictions

In response to the safety concerns, the FDA implemented several measures to limit the use of cisapride. These included prospective drug utilization review edits denying reimbursement for cisapride due to drug interactions and a "medical exception only" reimbursement policy. These restrictions significantly impacted the drug's utilization even before its official withdrawal from the market[1].

Market Withdrawal

In July 2000, Janssen Pharmaceutica announced its decision to withdraw cisapride from the market due to the serious cardiac risks associated with its use. This decision was a culmination of the regulatory pressures and the growing evidence of the drug's adverse effects.

Impact on Utilization of Other GI Agents

The withdrawal of cisapride led to a shift in the utilization of other gastrointestinal agents. A study analyzing prescription data found that while the use of cisapride decreased precipitously, the use of metoclopramide, another prokinetic agent, increased. However, this increase was not proportional to the decline in cisapride use, indicating that other treatment options were also being explored[1].

Financial Trajectory

Revenue Impact

The financial impact of cisapride's withdrawal was significant for Janssen Pharmaceutica and the broader pharmaceutical market. While the drug was a major revenue generator during its peak, its withdrawal led to a loss of revenue for the company. However, the overall program-wide costs for gastrointestinal drugs did not significantly increase due to the withdrawal, as other treatments filled the gap[1].

Licensing and Partnership Implications

Although cisapride itself was no longer a revenue source, the experience highlighted the importance of robust safety monitoring and the need for diverse product portfolios. Companies like Ironwood Pharmaceuticals, which focused on developing and commercializing other gastrointestinal treatments like linaclotide, emphasized the importance of strategic partnerships and diversified revenue streams to mitigate such risks[3].

Long-term Clinical and Market Implications

Clinical Impact

The withdrawal of cisapride resulted in increased use of metoclopramide, which has a more serious adverse effect profile. This shift underscored the need for continuous monitoring of drug safety and the importance of having multiple treatment options available to patients. Further studies were recommended to evaluate the long-term clinical impact of such therapy changes[1].

Market Lessons

The cisapride case serves as a cautionary tale for pharmaceutical companies. It highlights the critical importance of robust post-marketing surveillance and the potential financial and reputational risks associated with drugs that pose significant safety concerns. The FDA's handling of cisapride also raised questions about the agency's ability to balance the need for new treatments with the necessity of ensuring drug safety[5].

Key Takeaways

• Safety Concerns: Cisapride's market trajectory was drastically altered by its serious cardiac side effects.
• Regulatory Actions: FDA warnings and restrictions significantly reduced the drug's use before its official withdrawal.
• Market Impact: The withdrawal led to increased use of other gastrointestinal agents, particularly metoclopramide.
• Financial Impact: The loss of cisapride as a revenue source was mitigated by the lack of significant increase in overall program-wide costs for GI drugs.
• Long-term Implications: The case emphasizes the importance of robust safety monitoring and diversified product portfolios.

FAQs

Q: What was the primary reason for the withdrawal of cisapride from the market?

A: The primary reason was the discovery of serious cardiac side effects, including QT interval prolongation and torsades de pointes.

Q: How did the withdrawal of cisapride affect the use of other gastrointestinal agents?

A: The withdrawal led to an increase in the use of metoclopramide, although this increase was not proportional to the decline in cisapride use.

Q: What was the financial impact of cisapride's withdrawal on Janssen Pharmaceutica?

A: The withdrawal resulted in a loss of revenue from cisapride, but it did not significantly affect the overall program-wide costs for gastrointestinal drugs.

Q: What lessons can pharmaceutical companies learn from the cisapride case?

A: The case highlights the importance of robust post-marketing surveillance and the need for diversified product portfolios to mitigate risks associated with drug safety concerns.

Q: How did regulatory actions influence the market dynamics of cisapride?

A: Regulatory actions, including FDA warnings and restrictions, significantly reduced the use of cisapride even before its official withdrawal from the market.

Sources

1. Changes in related drug class utilization after market withdrawal of cisapride (Propulsid) - PubMed
2. ADVISORY COMMITTEE ON CIVIL RULES HEARING ON - US Courts
3. IRONWOOD PHARMACEUTICALS INC - Q4 CDN
4. Propulsid: Package Insert / Prescribing Information - Drugs.com
5. The adequacy of FDA to assure the safety of the nation's drug supply - GovInfo