Dolutegravir sodium; rilpivirine hydrochloride - Generic Drug Details

What are the generic drug sources for dolutegravir sodium; rilpivirine hydrochloride and what is the scope of patent protection?

Dolutegravir sodium; rilpivirine hydrochloride is the generic ingredient in one branded drug marketed by Viiv Hlthcare and is included in one NDA. There are five patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Dolutegravir sodium; rilpivirine hydrochloride has five hundred and five patent family members in fifty-eight countries.

One supplier is listed for this compound.

Summary for dolutegravir sodium; rilpivirine hydrochloride

International Patents:	505
US Patents:	5
Tradenames:	1
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for dolutegravir sodium; rilpivirine hydrochloride
DailyMed Link:	dolutegravir sodium; rilpivirine hydrochloride at DailyMed

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for dolutegravir sodium; rilpivirine hydrochloride

Constraining patent/regulatory exclusivity:

10,426,780

Dosage:

TABLET;ORAL

^*The generic entry opportunity date is the latter of the last compound-claiming patent and the last regulatory exclusivity protection. Many factors can influence early or later generic entry. This date is provided as a rough estimate of generic entry potential and should not be used as an independent source.

Pharmacology for dolutegravir sodium; rilpivirine hydrochloride

Drug Class	Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor Human Immunodeficiency Virus Integrase Strand Transfer Inhibitor
Mechanism of Action	HIV Integrase Inhibitors Multidrug and Toxin Extrusion Transporter 1 Inhibitors Non-Nucleoside Reverse Transcriptase Inhibitors Organic Cation Transporter 2 Inhibitors

Anatomical Therapeutic Chemical (ATC) Classes for dolutegravir sodium; rilpivirine hydrochloride

J05AG	Non-nucleoside reverse transcriptase inhibitors
J05A	DIRECT ACTING ANTIVIRALS
J05	ANTIVIRALS FOR SYSTEMIC USE
J	Antiinfectives for systemic use

J05AJ	Integrase inhibitors
J05A	DIRECT ACTING ANTIVIRALS
J05	ANTIVIRALS FOR SYSTEMIC USE
J	Antiinfectives for systemic use

Paragraph IV (Patent) Challenges for DOLUTEGRAVIR SODIUM; RILPIVIRINE HYDROCHLORIDE

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
JULUCA	Tablets	dolutegravir sodium; rilpivirine hydrochloride	50 mg/25 mg	210192	1	2019-11-19

US Patents and Regulatory Information for dolutegravir sodium; rilpivirine hydrochloride

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Viiv Hlthcare	JULUCA	dolutegravir sodium; rilpivirine hydrochloride	TABLET;ORAL	210192-001	Nov 21, 2017		RX	Yes	Yes	8,129,385*PED				Y
Viiv Hlthcare	JULUCA	dolutegravir sodium; rilpivirine hydrochloride	TABLET;ORAL	210192-001	Nov 21, 2017		RX	Yes	Yes	9,242,986*PED				Y
Viiv Hlthcare	JULUCA	dolutegravir sodium; rilpivirine hydrochloride	TABLET;ORAL	210192-001	Nov 21, 2017		RX	Yes	Yes	7,125,879		Y	Y
Viiv Hlthcare	JULUCA	dolutegravir sodium; rilpivirine hydrochloride	TABLET;ORAL	210192-001	Nov 21, 2017		RX	Yes	Yes	12,011,506		Y
Viiv Hlthcare	JULUCA	dolutegravir sodium; rilpivirine hydrochloride	TABLET;ORAL	210192-001	Nov 21, 2017		RX	Yes	Yes	10,426,780		Y	Y

Expired US Patents for dolutegravir sodium; rilpivirine hydrochloride

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Viiv Hlthcare	JULUCA	dolutegravir sodium; rilpivirine hydrochloride	TABLET;ORAL	210192-001	Nov 21, 2017	6,838,464
Viiv Hlthcare	JULUCA	dolutegravir sodium; rilpivirine hydrochloride	TABLET;ORAL	210192-001	Nov 21, 2017	8,101,629
Viiv Hlthcare	JULUCA	dolutegravir sodium; rilpivirine hydrochloride	TABLET;ORAL	210192-001	Nov 21, 2017	8,080,551
Viiv Hlthcare	JULUCA	dolutegravir sodium; rilpivirine hydrochloride	TABLET;ORAL	210192-001	Nov 21, 2017	7,067,522

International Patents for dolutegravir sodium; rilpivirine hydrochloride

Country	Patent Number	Title	Estimated Expiration
Taiwan	200628155	HIV replication inhibiting pyrimidines
South Korea	101284361
Norway	339525
Brazil	0211909	Derivados de pirimidina que inibem o hiv
European Patent Office	3045206	DERIVE DE CARBAMOYLPYRIDONE POLYCYCLIQUE DOTE D'UNE ACTIVITE INHIBITRICE DE L'INTEGRASE DU VIH (POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY)
Ukraine	96568	ПОЛІЦИКЛІЧНЕ ПОХІДНЕ КАРБАМОЇЛПІРИДОНУ ЯК ІНГІБОР ВІЛ-ІНТЕГРАЗИ[ПОЛИЦИКЛИЧЕСКОЕ ПРОИЗВОДНОЕ КАРБАМОИЛПИРИДОНА КАК ИНГИБИТОР ВИЧ-ИНТЕГРАЗЫ (POLYCYCLIC CARBAMOYL PYRIDONE DERIVATIVE AS HIV-INTEGRASE INHIBITOR)
Malaysia	188334	ANTIVIRAL THERAPY

Supplementary Protection Certificates for dolutegravir sodium; rilpivirine hydrochloride

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
2465580	122021000021	Germany		PRODUCT NAME: CABOTEGRAVIR ODER EIN PHARMAZEUTISCH ANNEHMBARES SALZ ODER SOLVAT DAVON; REGISTRATION NO/DATE: EU/1/20/1481 20201217
1874117	2023C/545	Belgium		PRODUCT NAME: DOULUTEGRAVIR SODIQUE; AUTHORISATION NUMBER AND DATE: EU/1/13/892 20140121
1419152	PA2012009,C1419152	Lithuania		PRODUCT NAME: RILPIVIRINUM + TENOFOVIRUM DISOPROXILUM; REGISTRATION NO/DATE: EU/1/11/737/001, 2011 11 28 EU/1/11/737/002 20111128
2932970	SPC/GB18/041	United Kingdom		PRODUCT NAME: A COMBINATION COMPRISING DOLUTEGRAVIR OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF (E.G. DOLUTEGRAVIR SODIUM) AND RILPIVIRINE OR A PHARAMACEUTICALLY ACCEPTABLE SALT THEREOF (E.G. RILPIVIRINE HYDROCHLORIDE); REGISTERED: UK EU/1/18/1282 20180518; UK PLGB 35728/0055 20180518; UK PLGB 35728/0056 20180518; UK PLGB 35728/0057 20180518
1419152	SPC/GB12/025	United Kingdom		PRODUCT NAME: A COMBINATION OF RILPIVIRINE, A N-OXIDE, A PHARMACEUTICALLY ACCEPTABLE ADDITION SALT INCLUDING THE HYDROCHLORIC ACID SALT, OR A QUATERNARY AMINE THEREOF, AND TENOFOVIR, IN PARTICULAR TENOFOVIR DISOPROXIL FUMARATE.; REGISTERED: UK EU/1/11/737/001 20111128
1663240	93383	Luxembourg		PRODUCT NAME: COMBINAISON DE RILPIVIRINE OU UNE FORME THERAPEUTIQUE EQUIVALENTE QUI EN DERIVE TELLE QUE PROTEGEE PAR LE BREVET DE BASE, TEL QU'UN SEL PHARMACEUTIQUEMENT ACCEPTABLE DE RILPIVIRINE, INCLUANT LE SEL CHLORHYDRATE DE RILPIVIRINE,EMTRICITABINE, ET TENOFOVIR ALAFENAMIDE, OU UN SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CELUI-CI, EN PARTICULIER LE FUMARATE DE TENOFOVIR ALAFENAMIDE; AUTHORISATION NUMBER AND DATE: EU/1/16/1112 ODEFSEY - EMTRICITABINE
1663240	122015000088	Germany		PRODUCT NAME: KOMBINATION VON RILPIVIRIN ODER EINEM PHARMAZEUTISCH VERTRAEGLICHEN SALZ VON RILPIVIRIN, EINSCHLIESSLICH DES HYDROCHLORIDSALZES VON RILPIVIRIN, TENOFOVIR, INSBESONDERE TENOFOVIRDISOPROXILFUMARAT, UND EMTRICITABIN; REGISTRATION NO/DATE: EU/1/11/737/001-002 20111128

Dolutegravir sodium; rilpivirine hydrochloride Market Analysis and Financial Projection Experimental

Market Dynamics and Financial Trajectory of Juluca (Dolutegravir and Rilpivirine)

Introduction

Juluca, a fixed-dose combination tablet containing dolutegravir and rilpivirine, has marked a significant milestone in the treatment of HIV-1 infection. Approved by the US FDA in 2017, it is the first two-drug regimen available as a single pill for the maintenance treatment of HIV-1 in adults who are virologically suppressed[2].

Market Approval and Regulatory Landscape

The FDA approval of Juluca was based on data from the SWORD-1 and SWORD-2 phase III clinical trials, which demonstrated non-inferior viral suppression compared to traditional three- or four-drug regimens. This approval expanded treatment options for people living with HIV, offering a simpler and potentially less burdensome treatment regimen[2][5].

Clinical Trials and Efficacy

The SWORD trials, which included 1,024 participants, showed that the two-drug regimen of dolutegravir plus rilpivirine maintained viral suppression at levels comparable to those of three- or four-drug regimens. The trials also evaluated the development of viral resistance, safety, and tolerability, as well as changes in renal, bone, and cardiovascular biomarkers[2][5].

Market Impact

The introduction of Juluca has significantly impacted the HIV treatment market by offering a more streamlined treatment option. This two-drug regimen reduces the number of antiretrovirals patients need to take, which can improve adherence and reduce the long-term burden of treatment. According to Deborah Waterhouse, CEO of ViiV Healthcare, "This is the start of a new era in HIV treatment," highlighting the innovative approach and potential for improved patient outcomes[2].

Financial Trajectory

Revenue Potential

Juluca's approval and subsequent market entry have contributed to the revenue growth of ViiV Healthcare and its partners. As the first two-drug regimen, it has captured a significant share of the HIV treatment market, particularly among patients who are virologically suppressed and seeking simpler treatment options. The financial performance of Juluca is closely tied to its adoption rates and market penetration, which have been positive given its clinical efficacy and patient preference for fewer medications[2].

Pricing and Accessibility

The pricing of Juluca is a critical factor in its market dynamics. While the exact pricing details are not publicly disclosed in the sources, it is generally understood that the cost of antiretroviral therapies can be high. However, the simplicity and reduced pill burden of Juluca may offset some of these costs through improved adherence and reduced healthcare utilization over the long term. Efforts to make Juluca more accessible, including partnerships and pricing strategies, are likely to influence its financial trajectory[2].

Competitive Landscape

Juluca operates in a competitive market dominated by various antiretroviral therapies. However, its unique position as a two-drug regimen sets it apart. ViiV Healthcare's commitment to developing further two-drug regimens, such as dolutegravir/lamivudine and cabotegravir/rilpivirine, indicates a strategic focus on simplifying HIV treatment and reducing the lifetime burden of therapy. This approach is likely to maintain Juluca's competitive edge and contribute to its financial success[2].

Patient and Physician Preferences

Patient and physician preferences play a crucial role in the market dynamics of Juluca. The simplicity of a single-pill, two-drug regimen is highly appealing to patients, as it improves adherence and quality of life. Physicians also favor regimens that are easier to manage and have a lower risk of adverse events. The SWORD trials demonstrated low frequencies of drug-related adverse events and withdrawals, further enhancing Juluca's appeal to both patients and healthcare providers[1][2].

Safety and Tolerability

The safety profile of Juluca, as demonstrated in the SWORD trials, is a key factor in its market success. The regimen showed low rates of adverse events leading to discontinuation, with psychiatric disorders being the most common reason for discontinuation. The absence of significant laboratory abnormalities and the stable serum creatinine levels over 148 weeks of treatment further support its safety and tolerability[1].

Postmarketing Experience

Postmarketing surveillance has identified additional adverse reactions, including hepatobiliary disorders, musculoskeletal disorders, and severe skin and hypersensitivity reactions. However, these reactions are rare and do not significantly impact the overall safety profile of Juluca. Continuous monitoring and reporting of adverse events will be crucial in maintaining trust and ensuring the long-term success of the drug[1].

Global Expansion

Juluca has received marketing approvals in several countries, including the US and Japan. This global expansion is expected to further boost its revenue and market presence. The approval by the Japan Ministry of Health, Labour and Welfare in 2018 marked another significant milestone in Juluca's global reach[5].

Key Takeaways

• Innovative Treatment Option: Juluca is the first two-drug regimen approved for the maintenance treatment of HIV-1 infection.
• Clinical Efficacy: Demonstrated non-inferior viral suppression compared to traditional three- or four-drug regimens.
• Market Impact: Simplifies treatment, improves adherence, and reduces the long-term burden of therapy.
• Financial Trajectory: Positive revenue growth due to its unique position and patient preference.
• Competitive Edge: Unique two-drug regimen sets it apart in a competitive market.
• Safety and Tolerability: Low rates of adverse events and stable laboratory parameters.

FAQs

What is Juluca, and how is it used?

Juluca is a fixed-dose combination tablet containing dolutegravir and rilpivirine, used for the maintenance treatment of HIV-1 infection in adults who are virologically suppressed. It is taken once daily with a meal.

What were the key findings of the SWORD trials?

The SWORD trials showed that the two-drug regimen of dolutegravir plus rilpivirine achieved non-inferior viral suppression compared to traditional three- or four-drug regimens, with low frequencies of adverse events and withdrawals.

How does Juluca impact the HIV treatment market?

Juluca simplifies HIV treatment by reducing the number of antiretrovirals patients need to take, improving adherence and reducing the long-term burden of therapy. This has captured a significant share of the HIV treatment market.

What are the common adverse reactions associated with Juluca?

Common adverse reactions include psychiatric disorders, increases in serum creatinine, and changes in serum lipids. Rare but serious reactions include hepatobiliary disorders and severe skin and hypersensitivity reactions.

Is Juluca available globally?

Yes, Juluca has received marketing approvals in several countries, including the US and Japan, and is part of ViiV Healthcare's global expansion strategy.

Sources

1. RxList: Juluca (Dolutegravir and Rilpivirine Tablets, for Oral Use) - RxList
2. GSK: Juluca® (dolutegravir and rilpivirine) approved in US as first 2-drug regimen once-daily single pill
3. Pharmaceuticals.gov.in: An Analysis on leveraging the patent cliff with drug sales worth USD 251 billion going off-patent
4. FDA: 210192Orig1s000 - accessdata.fda.gov
5. GSK: Juluca (dolutegravir/rilpivirine), the first single pill, 2-drug regimen for the maintenance treatment of HIV granted marketing approval by Japan Ministry of Health, Labour and Welfare