Press Release: Aurobindo Pharma receives USFDA tentative approval for Dolutegravir
Published September 22nd, 2016
22 September 2016, Hyderabad, India
Aurobindo Pharma receives USFDA tentative approval for Dolutegravir, allowing the product to be launched in the PEPFAR market
Aurobindo Pharma Limited is pleased to announce the tentative approval of Dolutegravir 50mg from US Food & Drug Administration (USFDA) for the treatment of HIV. This important milestone marks the first FDA approval of a generic version of Dolutegravir (DTG), an integrase strand transfer inhibitor recommended for use in treatment-naïve patients by the US Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO). Through an innovative collaboration with ViiV and the Clinton Health Access Initiative, Inc. (CHAI), the product is expected to be launched in sub-Saharan Africa in late 2016.
The approved Abbreviated New Drug Application (ANDA) is bioequivalent and therapeutically equivalent to the reference listed drug product (RLD) Tivicay®, of ViiV Healthcare.
ViiV Healthcare and Aurobindo Pharma signed a licensing agreement in 2014 that allows Aurobindo Pharma to supply Dolutegravir 50mg in 92 licensed countries, following completion of required local regulatory approval processes.
Commenting on the development, Mr. N. Govindarajan, Managing Director of Aurobindo Pharma Limited said:
"The approval of the generic version of DTG shows the commitment towards the larger cause of bringing affordable HIV drugs to millions of people. This is a one-of-its-kind agreement between innovator and generic company where the generic version of the drug will be launched in around three years from the originator product. Further, we are also developing a fixed dose combination of DTG."
David Ripin, Executive Vice President of the Clinton Health Access Initiative, Inc. notes,
"Dolutegravir is a critical new tool that will help us achieve the UNAIDS 90-90-90 goals and an AIDS-free generation. The WHO included Dolutegravir in its recommendations for first-line therapy in 2015, and we expect rapid growth in demand now that a cost-effective generic product is available. Dolutegravir, taken with other HIV treatments, has the potential to improve the lives of millions of patients."
Dolutegravir 50mg is indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents.
About Aurobindo Pharma
Aurobindo Pharma Limited (www.aurobindo.com) (NSE: AUROPHARMA, BSE: 524804, Reuters: ARBN.NS, Bloomberg: ARBP:IN), headquartered at Hyderabad, India, manufactures generic pharmaceuticals and active pharmaceutical ingredients. A vertically integrated pharmaceutical company that delivers innovative solutions and leverages India's globally competitive cost base and talented team of scientists to discover, develop, and commercialize a range of affordable medicines for markets across the globe. The company's manufacturing facilities are approved by several leading regulatory agencies like US FDA, UK MHRA, Japan PMDA, WHO, Health Canada, MCC South Africa, ANVISA Brazil. The company's robust product portfolio is spread over 7 major therapeutic/product areas encompassing Antibiotics, Anti-Retrovirals, CVS, CNS, Gastroenterologicals, Anti-Allergies and Anti-Diabetics, supported by an outstanding R&D set-up. The Company is marketing these products globally, in over 150 countries.
About Clinton Health Access Initiative, Inc.
The Clinton Health Access Initiative, Inc. (CHAI) is a global health organization committed to strengthening integrated health systems and expanding access to care and treatment in the developing world. CHAI's solution-oriented approach focuses on improving market dynamics for medicines and diagnostics; lowering prices for treatment; accelerating access to lifesaving technologies; and helping governments build the capacity required for high-quality care and treatment programs. For more information, please visit:
ViiV Healthcare welcomes the FDA's Tentative Approval of the first generic dolutegravir from Aurobindo Pharma
22 Sep 2016
ViiV Healthcare welcomes today's decision by the US Food and Drug Administration (FDA) to grant Aurobindo Pharma Tentative Approval for the first generic version of dolutegravir 50mg for the treatment of HIV in the developing world.
"We think that this Tentative Approval of the first generic dolutegravir from Aurobindo will improve access to dolutegravir in the developing world for those patients in need," said Dr Dominique Limet, Chief Executive Officer, ViiV Healthcare. "It is great to see our access strategy deliver progress in bringing recently approved ARVs like dolutegravir to patients in countries where the burden of HIV is greatest in a timely manner, in this case just over three years since it was first made available in the Unites States and just under three years since it was first made available in Europe."
The approval is a prerequisite for Aurobindo's product to be supplied under the President's Emergency Plan for Aids Relief (PEPFAR) programme. The submission was supported by ViiV Healthcare and the Clinton Access Initiative (CHAI), in accordance with their agreement to support the development and introduction of innovative formulations of medicines to treat people living with HIV in developing countries on an affordable yet sustainable basis.
Globally, there are more than 36 million people living with HIV. Scaling-up HIV treatment in low- and middle-income countries over the past 15 years is one of the greatest success stories in global health and ensuring that all people living with HIV have access to HIV medicines is a crucial part of the global response to the epidemic.
Dolutegravir is an integrase strand transfer inhibitor (INSTI) for use in combination with other antiretroviral agents for the treatment of HIV. Integrase inhibitors block HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection. Dolutegravir is currently recommended by the World Health Organisation (WHO) as an alternative first-line therapy for the treatment of HIV in adults and adolescents 12 years and older.
Professional Indication(s) and Important Safety Information about TIVICAY® (dolutegravir) tablets:
Note: this is taken from the US label and local variations apply. Please refer to applicable local labelling
FDA Indications and Usage
TIVICAY® is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 30 kg.
Limitations of Use:
Use of TIVICAY in INSTI-experienced patients should be guided by the number and type of baseline INSTI substitutions. The efficacy of TIVICAY 50 mg twice daily is reduced in patients with an INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions including T66A, L74I/M, E138A/K/T, G140S/A/C, Y143R/C/H, E157Q, G163S/E/K/Q, or G193E/R
Important Safety Information
TIVICAY is contraindicated in patients:
• with previous hypersensitivity reaction to dolutegravir
• receiving dofetilide (antiarrhythmic)
• Hypersensitivity reactions have been reported and were characterised by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in <1% of subjects receiving TIVICAY in Phase 3 clinical trials
• Discontinue TIVICAY and other suspect agents immediately if signs or symptoms of hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. Monitor clinical status, including liver aminotransferases, and initiate appropriate therapy if hypersensitivity reaction is suspected
Effects on Serum Liver Biochemistries in Patients with Hepatitis B or C Co-infection:
• Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with use of TIVICAY. In some cases the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn
• Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with TIVICAY are recommended in patients with underlying hepatic disease such as hepatitis B or C
Fat Redistribution or accumulation has been observed in patients receiving antiretroviral therapy
Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported
Adverse Reactions: The most commonly reported (≥2%) adverse reactions of moderate to severe intensity in treatment-naïve adult subjects in any one trial receiving TIVICAY in a combination regimen were insomnia (3%), fatigue (2%), and headache (2%).
• Coadministration of TIVICAY with certain inducers of UGT1A and/or CYP3A may reduce plasma concentrations of dolutegravir and require dose adjustments of TIVICAY
• Administer TIVICAY 2 hours before or 6 hours after taking polyvalent cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, TIVICAY and supplements containing calcium or iron can be taken with food
• Consult the full Prescribing Information for TIVICAY for more information on potentially significant drug interactions, including clinical comments
Pregnancy: TIVICAY should be used during pregnancy only if the potential benefit justifies the potential risk. An Antiretroviral Pregnancy Registry has been established.
Nursing Mothers: Breastfeeding is not recommended due to the potential for HIV transmission and the potential for adverse reactions in nursing infants.
 UNAIDS Factsheet. July 2016.Available at:
http://www.unaids.org/en/resources/fact-sheet. Last accessed July 2016.
 UNAIDS. How AIDS Changed Everything. Available at:
http://www.unaids.org/sites/default/files/media_asset/MDG6Report_en.pdf. Last accessed: September 2016.
 WHO. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Available at: http://www.who.int/hiv/pub/arv/arv-2016/en/. Last accessed: July 2016.
ViiV Healthcare and CHAI collaboration delivers second milestone with first filing with the FDA of generic dolutegravir by Aurobindo Pharma for the treatment of HIV
London, May 26, 2015 - ViiV Healthcare, Aurobindo Pharma, and the Clinton Health Access Initiative, Inc. (CHAI) announced today that Aurobindo Pharma has submitted an Abbreviated New Drug Application (ANDA) for dolutegravir 50mg, for Tentative Approval, to the Food and Drug Administration (FDA), for the treatment of HIV. This is the first ANDA for a generic version of dolutegravir, less than two years after FDA approval of Tivicay® (dolutegravir) for sale in the United States.
Upon receiving Tentative Approval from the FDA, Aurobindo Pharma will be able to supply dolutegravir 50mg via the President's Emergency Plan for AIDS Relief (PEPFAR) programme, following completion of required local regulatory approval process, in the licensed countries outside of the United States, as per the agreement signed between Aurobindo Pharma and ViiV Healthcare in 2014.
This submission comes less than five years after ViiV Healthcare and CHAI signed an agreement to collaborate with the goal of bringing innovative formulations of medicines for the treatment and prevention of HIV/AIDS to people living with HIV in developing countries, on an affordable yet sustainable basis.
CHAI and ViiV Healthcare worked together to identify a generic partner after conducting feasibility research. Following this initial joint work, ViiV Healthcare submitted necessary documentation to the FDA providing a selective waiver letter for the five-year period of New Chemical Entity (NCE) exclusivity that would have otherwise prevented FDA review and Tentative Approval of Aurobindo Pharma's ANDA at this time.
Dr. Dominique Limet, CEO, ViiV Healthcare, said: "This first ANDA for a generic dolutegravir confirms that our strong commitment to thinking and acting differently to pursue new ways to expand access to our medicines, for people living with HIV in countries where the need is most pressing, is working."
David Ripin, PhD, Executive Vice President, and Chief Scientific Officer, CHAI, said: "UNAIDS has set global public health goals calling for 90 percent of those who are HIV-positive to know their status, 90 percent of those identified to be linked to treatment programs, and 90 percent of those in treatment to achieve undetectable viral load. To tackle these complex challenges, targeted efforts to facilitate access to HIV treatment medicines, such as dolutegravir, are needed."
Mr. N. Govindarajan, Managing Director, Aurobindo Pharma, said: "We are pleased to be part of this innovative partnership designed to accelerate access to medicines for treating HIV. Aurobindo Pharma is committed to HIV care and aims to achieve the goals of wider access to HIV treatment, care, and support; seeking to address the spread of HIV through development of this newer class of drugs and fixed-dose combinations for low- and middle-income countries. "
The filing by Aurobindo Pharma is the second result of the agreement between CHAI and ViiV Healthcare and comes less than six months after another generic manufacturer announced that it had received Tentative Approval from the FDA for paediatric formulations of another ViiV Healthcare antiretroviral (also under PEPFAR for sale in licensed countries outside of the United States), through innovative collaboration with ViiV Healthcare and CHAI.
About Clinton Health Access Initiative
The Clinton Health Access Initiative, Inc. (CHAI) was founded in 2002 with a transformational goal: help save the lives of millions of people living with HIV/AIDS in the developing world by dramatically scaling up antiretroviral treatment. When CHAI was founded, many viewed this goal as unreasonable because health systems in poor countries were too weak and prices of relevant drugs and diagnostic tests were too high. CHAI played a leadership role, working alongside governments and other partners, to lower the costs of treatment and help build the in-country systems necessary to provide lifesaving treatment to millions of people. Since then, CHAI has pursued several similarly ambitious goals, from scaling up pediatric AIDS treatment in order to achieve equity with adults in a timeframe few thought possible, to rapidly accelerating the rollout of new vaccines. CHAI has achieved many of its most important successes when seeking to fundamentally change the way the world approaches an issue and pushing the boundaries of what is considered feasible in global health. For more information, please visit:www.clintonhealthaccess.org
About ViiV Healthcare
ViiV Healthcare is a global specialist HIV company established in November 2009 by GlaxoSmithKline (LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in treatment and care for people living with HIV. Shionogi joined as a shareholder in October 2012. The company's aim is to take a deeper and broader interest in HIV/AIDS than any company has done before and take a new approach to deliver effective and new HIV medicines, as well as support communities affected by HIV. For more information on the company, its management, portfolio, pipeline, and commitment, please visit www.viivhealthcare.com.
About Aurobindo Pharma
Aurobindo Pharma Ltd. is a vertically integrated pharmaceutical company that delivers innovative solutions. Aurobindo Pharma leverages India's globally competitive cost base and talented team of scientists to discover, develop, and commercialize a range of affordable medicines for markets across the globe. For more information, please visit www.aurobindo.com.
About President's Emergency Plan for AIDS Relief (PEPFAR)
PEPFAR is the US government initiative to help save the lives of those suffering from HIV/AIDS around the world. This historic commitment is the largest by any nation to combat a single disease internationally. In May 2004, in support of the President's Emergency Plan, the FDA announced a new initiative to help ensure that those being served by the President's Plan would receive safe, effective, and quality manufactured antiretroviral drugs. This new initiative included an expedited review process. Through guidance and an active outreach program to the pharmaceutical industry, the FDA actively encouraged any sponsors worldwide to submit US marketing applications for single entity, fixed dose combination (FDC), and co-packaged versions of previously approved antiretroviral therapies-even if there was still patent or exclusivity market protection for the product in the US.
Important Information about Tivicay® (dolutegravir) in the US
FDA Indication and Usage: TIVICAY is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Use of TIVICAY in INSTI-experienced patients should be guided by the number and type of baseline INSTI substitutions. The efficacy of TIVICAY 50 mg twice daily is reduced in patients with an INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions including T66A, L74I/M, E138A/K/T, G140S/A/C, Y143R/C/H, E157Q, G163S/E/K/Q, or G193E/R.
Important Safety Information for Tivicay® (dolutegravir)
Contraindication: TIVICAY is contraindicated (1) in patients with previous hypersensitivity reaction to dolutegravir, and (2) in patients receiving dofetilide (antiarrhythmic) due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events.
Hypersensitivity Reactions: Hypersensitivity reactions have been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in 1% or fewer subjects receiving TIVICAY in Phase 3 clinical trials. Discontinue TIVICAY and other suspect agents immediately if signs or symptoms of hypersensitivity reaction develop, (including but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing.) Monitor clinical status, including liver aminotransferases, and initiate appropriate therapy. Delay in stopping treatment with TIVICAY or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction. TIVICAY is contraindicated in patients who have experienced a hypersensitivity reaction to dolutegravir.
Effects on Serum Liver Biochemistries in Patients with Hepatitis B or C Coinfection: Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with use of TIVICAY. In some cases the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation particularly in the setting where anti-hepatitis therapy was withdrawn. Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with TIVICAY are recommended in patients with underlying hepatic disease such as hepatitis B or C.