SUBSYS Drug Patent Profile

Which patents cover Subsys, and when can generic versions of Subsys launch?

Subsys is a drug marketed by Btcp Pharma and is included in one NDA. There are ten patents protecting this drug and two Paragraph IV challenges.

This drug has thirty-two patent family members in seventeen countries.

The generic ingredient in SUBSYS is fentanyl. There are thirty-one drug master file entries for this compound. Eight suppliers are listed for this compound. Additional details are available on the fentanyl profile page.

DrugPatentWatch^® Generic Entry Outlook for Subsys

There have been three patent litigation cases involving the patents protecting this drug, indicating strong interest in generic launch. Recent data indicate that 63% of patent challenges are decided in favor of the generic patent challenger and that 54% of successful patent challengers promptly launch generic drugs.

There are two tentative approvals for the generic drug (fentanyl), which indicates the potential for near-term generic launch.

Indicators of Generic Entry

Summary for SUBSYS

International Patents:	32
US Patents:	10
Applicants:	1
NDAs:	1
Raw Ingredient (Bulk) Api Vendors:	38
Clinical Trials:	5
Patent Applications:	2,596
Drug Prices:	Drug price information for SUBSYS
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for SUBSYS
What excipients (inactive ingredients) are in SUBSYS?	SUBSYS excipients list
DailyMed Link:	SUBSYS at DailyMed

See drug prices for SUBSYS

Recent Clinical Trials for SUBSYS

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

Sponsor	Phase
INSYS Therapeutics Inc	N/A
Loyola University	Phase 3
INSYS Therapeutics Inc	Phase 3

See all SUBSYS clinical trials

Paragraph IV (Patent) Challenges for SUBSYS

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
SUBSYS	Sublingual Spray	fentanyl	0.1 mg/spray, 0.2 mg/spray, 0.6 mg/spray, 0.8 mg/spray, 1.2 mg/spray, 1.6 mg/spray	202788	1	2017-12-07
SUBSYS	Sublingual Spray	fentanyl	0.4 mg/spray	202788	1	2017-05-22

US Patents and Regulatory Information for SUBSYS

SUBSYS is protected by ten US patents.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-005	Jan 4, 2012		DISCN	Yes	No	9,289,387		Y
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-004	Jan 4, 2012		DISCN	Yes	No	8,486,973
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-006	Aug 30, 2012		DISCN	Yes	No	8,486,973
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-007	Aug 30, 2012		DISCN	Yes	No	9,642,797		Y
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-005	Jan 4, 2012		DISCN	Yes	No	10,610,523		Y
Btcp Pharma	SUBSYS	fentanyl	SPRAY;SUBLINGUAL	202788-006	Aug 30, 2012		DISCN	Yes	No	9,289,387		Y

EU/EMA Drug Approvals for SUBSYS

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Kyowa Kirin Holdings B.V.	PecFent	fentanyl	EMEA/H/C/001164 PecFent is indicated for the management of breakthrough pain in adults who are already receiving maintenance opioid therapy for chronic cancer pain. Breakthrough pain is a transitory exacerbation of pain that occurs on a background of otherwise controlled persistent pain.Patients receiving maintenance opioid therapy are those who are taking at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equi-analgesic dose of another opioid for a week or longer.	Authorised	no	no	no	2010-08-31
Takeda Pharma A/S	Instanyl	fentanyl	EMEA/H/C/000959 Instanyl is indicated for the management of breakthrough pain in adults already receiving maintenance opioid therapy for chronic cancer pain. Breakthrough pain is a transitory exacerbation of pain that occurs on a background of otherwise controlled persistent pain. Patients receiving maintenance opioid therapy are those who are taking at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.	Authorised	no	no	no	2009-07-20
Teva B.V.	Effentora	fentanyl	EMEA/H/C/000833 Effentora is indicated for the treatment of breakthrough pain (BTP) in adults with cancer who are already receiving maintenance opioid therapy for chronic cancer pain., , BTP is a transitory exacerbation of pain that occurs on a background of otherwise controlled persistent pain., , Patients receiving maintenance opioid therapy are those who are taking at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer. ,	Authorised	no	no	no	2008-04-04
Incline Therapeutics Europe Ltd	Ionsys	fentanyl	EMEA/H/C/002715 Ionsys is indicated for the management of acute moderate to severe post-operative pain in adult patients.	Withdrawn	no	no	no	2015-11-18
Eli Lilly and Company Limited	Recuvyra	fentanyl	EMEA/V/C/002239 For the control of pain associated with orthopaedic and soft tissue surgery in dogs.	Withdrawn	no	no	no	2011-10-06
Janssen-Cilag International NV	Ionsys	fentanyl	EMEA/H/C/000612 Management of acute moderate to severe post-operative pain for use in a hospital setting only	Withdrawn	no	no	no	2006-01-24	2008-07-25

International Patents for SUBSYS

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

Country	Patent Number	Title	Estimated Expiration
Cyprus	1117263
Canada	2637672	SUBLINGUAL FENTANYL SPRAY
Japan	2013056928	SUBLINGUAL FENTANYL SPRAY
Japan	2009528272
Canada	2698749	AEROSOL SUBLINGUAL DE FENTANYL (SUBLINGUAL FENTANYL SPRAY)
Japan	5241514

Supplementary Protection Certificates for SUBSYS

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
1635783	300653	Netherlands		PRODUCT NAME: FENTANYL IN ELKE DOOR HET BASISOCTROOI BESCHERMDE VERSCHIJNINGSVORM; REGISTRATION NO/DATE: EU/1/10/644/001-004 20100906
1635783	CA 2014 00016	Denmark		PRODUCT NAME: FENTANYL I EN HVILKEN SOM HELST AF DE FORMER, DER ER BESKYTTET AF GRUNDPATENTET; REG. NO/DATE: EU/1/10/644/001-006 20100831
0901368	C300523	Netherlands		PRODUCT NAME: FENTANYL; REGISTRATION NO/DATE: EU/2/11/127/001 20111006
1769785	C300521	Netherlands		PRODUCT NAME: FENTANYL; REG NO/DATE: EU/2/11/127/001 20111006
0975367	122011000009	Germany		PRODUCT NAME: FENTANYL IN ALLEN DEM SCHUTZ DES GRUNDPATENTS UNTERLIEGENDEN FORMEN; REGISTRATION NO/DATE: EU/1/10/644/001-004 20100831
0836511	CA 2006 00019	Denmark		PRODUCT NAME: FENTANYL HYDROCHLORID

Market Dynamics and Financial Trajectory of Subsys

Introduction

Subsys, a sublingual fentanyl spray developed by Insys Therapeutics, was approved by the FDA in January 2012 for the treatment of breakthrough pain in opioid-tolerant cancer patients. Despite its narrow FDA-approved indication, the drug's market dynamics and financial trajectory were marked by both rapid growth and severe controversy.

FDA Approval and Initial Launch

Subsys was approved for a specific and narrow indication: treating breakthrough pain in cancer patients who were already tolerant to around-the-clock opioid therapy. The drug was part of a class known as transmucosal immediate-release fentanyl (TIRF) products, which are significantly more potent than morphine and heroin[2][4].

Lackluster Initial Sales

The initial launch of Subsys in the spring of 2012 was met with lackluster sales. For the first six months, prescriptions were scarce, with only a couple of prescriptions written per week. This performance was deemed unacceptable by Insys' founder, John Kapoor, who described it as "the worst launch in pharmaceutical history"[1].

Strategic Shift and Aggressive Marketing

To boost sales, Insys brought in Alec Burlakoff, a seasoned pharmaceutical sales executive, as the new national director of sales. Burlakoff implemented a aggressive marketing strategy that focused on targeting healthcare providers and pressuring them to prescribe Subsys at higher doses and for broader indications than approved by the FDA.

Targeting and Titration

Burlakoff's strategy involved identifying the "hot buttons" of healthcare providers and using these to influence their prescribing habits. This included a directive from Kapoor to implement an "effective dose" campaign, which was essentially about titrating patients to higher doses of Subsys. Sales reps were incentivized to push for these higher doses, which significantly increased the revenue generated per prescription[1].

Off-Label Marketing and Bribery

Insys devised a subversive and illegal plan to promote Subsys for uses beyond its FDA-approved label. The company directed its sales force to push healthcare providers to write Subsys prescriptions for chronic pain of any type, despite the dangers associated with such off-label use. Insys also paid healthcare providers with sham speaking and consulting fees to encourage these prescriptions. Additionally, the company fraudulently induced insurers to pay for these off-label prescriptions by misrepresenting patients' diagnoses and treatment histories[2][3].

Financial Impact

Revenue Growth

The aggressive marketing and off-label promotion strategies led to a significant increase in Subsys sales. By 2013, Insys had gone public, and Subsys sales were driving the company's revenue. Insys's net revenues were approximately 98% attributed to Subsys sales from its launch in 2012 through the third quarter of 2016[2].

High-Value Prescriptions

A single prescription of Subsys could be worth up to $60,000 per month to the company, making it a highly lucrative product. In New Jersey alone, Insys sold approximately $74.2 million worth of Subsys from 2012 through the third quarter of 2016, with a significant portion of this amount paid by state health benefit programs[2].

Regulatory and Legal Challenges

FDA Oversight and REMS Program

Subsys was part of the FDA's Transmucosal Immediate-release Fentanyl (TIRF) Risk Evaluation and Mitigation Strategy (REMS) program, designed to ensure safe use of these potent opioids. However, Insys's actions circumvented these safety measures, leading to widespread misuse and abuse of the drug[4].

Legal Consequences

Insys and its executives faced severe legal consequences for their actions. In 2019, a federal jury convicted Kapoor and four other Insys executives of racketeering conspiracy. Kapoor was sentenced to five-and-a-half years in federal prison and ordered to pay a multi-million dollar fine. The State of New Jersey also took action against doctors who had indiscriminately prescribed Subsys, leading to several doctors being barred from practice[3].

Settlements and Penalties

In 2021, Attorney General Gurbir S. Grewal announced a $5 million settlement with John Kapoor to resolve allegations of orchestrating a nationwide kickback scheme to boost Subsys sales. The settlement funds were to be used to combat the opioid epidemic and reimburse state agencies affected by the fraudulent scheme[3].

Human Impact

Overdoses and Deaths

The aggressive and illegal marketing of Subsys led to devastating consequences. In New Jersey, at least one resident died from a Subsys-related overdose, and hundreds of other lives were put in jeopardy. The misuse of Subsys contributed to the broader opioid epidemic, highlighting the dangers of off-label prescribing and the importance of adhering to FDA-approved indications[2][3].

Key Takeaways

• Narrow FDA Approval: Subsys was approved only for treating breakthrough pain in opioid-tolerant cancer patients.
• Aggressive Marketing: Insys used aggressive and illegal marketing strategies to boost sales, including off-label promotion and bribery.
• Financial Success: Despite initial lackluster sales, Subsys became a highly lucrative product, driving nearly all of Insys's revenue.
• Regulatory and Legal Issues: Insys faced severe regulatory and legal consequences, including convictions and significant fines.
• Human Impact: The misuse of Subsys contributed to the opioid epidemic, resulting in overdoses and deaths.

FAQs

What was Subsys approved for by the FDA?

Subsys was approved by the FDA for the treatment of breakthrough pain in opioid-tolerant cancer patients[2][4].

How did Insys increase sales of Subsys?

Insys increased sales through aggressive marketing strategies, including targeting healthcare providers, pressuring them to prescribe higher doses, and promoting the drug for off-label uses[1][2].

What were the legal consequences for Insys and its executives?

Insys executives, including John Kapoor, were convicted of racketeering conspiracy and faced significant fines and prison sentences. Kapoor was sentenced to five-and-a-half years in federal prison[3].

How much revenue did Subsys generate for Insys?

Subsys accounted for approximately 98% of Insys's net revenues from its launch in 2012 through the third quarter of 2016[2].

What was the human impact of the misuse of Subsys?

The misuse of Subsys led to overdoses, deaths, and heightened risks of addiction and overdose among patients, contributing to the broader opioid epidemic[2][3].

Sources

1. PBS: Opioids, Inc. - Transcript - PBS
2. NJ.gov: Insys-Complaint.pdf
3. NJ Office of the Attorney General: AG Grewal Announces Multi-Million Dollar Settlement with Insys Therapeutics Founder John Kapoor
4. FDA: Overdose Prevention Activities Timeline
5. CrimeReads: The Pharma Startup That Went from Treating Cancer Patients to Fueling the Opioid Epidemic