Prescription medicines and biologicals: TGA annual summary 2017
In 2017
34 New chemical or biological entity registrations
46 New or extended uses, or new combination registrations
21 Orphan Drug registrations
101 New generic medicine registrations
69 AusPAR publications
New chemical or biological entity registrations by year
New generic medicine registrations by year
Introduction
The Therapeutic Goods Administration (TGA) is the regulator responsible for approving prescription medicines for human use in Australia through an evaluation of their quality, safety and efficacy. This includes entirely new medicines (termed 'new chemical or biological entities'), new uses ('extension of indications') or combinations of already-registered medicines, and new generic and biosimilar medicines. If approved, these medicines are added to the Australian Register of Therapeutic Goods (ARTG) and can be lawfully supplied in Australia, and prescribed by healthcare professionals for specific indications. In addition to evaluating prescription medicines, TGA's regulatory ambit includes complementary and over-the-counter medicines, medical devices, vaccines, cell and tissue products, blood and blood products, and other therapeutic goods such as sunscreens. As part of the Health Products Regulation Group (HPRG) within the Australian Commonwealth Department of Health, we contribute to the protection and promotion of public health by supporting timely access to this vast array of therapeutic goods.
This is TGA's fourth annual summary report on the registration of prescription medicines, which includes new generic and biosimilar medicines. The summary also showcases new biologicals, including human cell- and tissue-derived products; and Australian Public Assessment Reports (AusPARs) published on our website during 2017. For the first time, the summary contains Priority review determinations. Priority review involves a faster assessment of certain prescription medicines, with a 3-month shorter timeframe than the standard registration process.
This year's registrations covered a wide therapeutic base with new treatments for conditions that include cancers, schizophrenia and meningococcal disease. During this period, two new first-in-class treatments were approved for spinal muscular atrophy and liposomal acid lipase deficiency. Orphan drugs for the treatment of rare diseases were approved for haemophilia and Fabry disease. Notably, 2017 saw a large proportion of new registrations of immunotherapies and human monoclonal antibodies, while the listing of new 'first generic' medicines triggered a statutory 16% price reduction under the Pharmaceutical Benefits Scheme. The registration of these new medicines provides the Australian public with a broader and more affordable range of treatment options, which will serve to enhance public health. Today, TGA's approval times for prescription medicines are comparable with analogous registration processes in the US and Europe. As for 2016, these approval times have fallen in 2017 with continual business improvements, and are anticipated to further fall following the introduction of Priority review pathways.
It gives me great pleasure to publish the 2017 annual summary report. We hope this information is of interest and use to the public, healthcare professionals, government bodies, other medicines regulators, and industry as we work together towards better health outcomes for all Australians.
Adjunct Professor John Skerritt
Deputy Secretary, Health Products Regulation Group
Department of Health
January 2018
Some innovative and 'first-in-class' new registrations
Please note that the indication for which each prescription medication is approved may be more specific than as described in general terms in this summary. For the full approved indications, please consult the Australian Register of Therapeutic Goods (ARTG).
DARZALEX
Darzalex (daratumumab) is used in combination with other drugs for the treatment of multiple myeloma, a form of blood cancer arising from plasma cells in bone marrow. Darzalex is a human monoclonal antibody that works together with immune system cells to help clear myeloma from the body. By targeting and attaching to CD38, a molecule overexpressed on the surface of multiple myeloma cells, Darzalex instigates an immune reaction that ultimately causes these dangerous cells to die.
INTUNIV
Intuniv (guanfacine) is the first once-daily, extended-release, non-stimulant drug approved for the treatment of attention deficit hyperactivity disorder (ADHD) in children. As a highly selective agonist of the alpha-2A adrenergic receptor, a molecule with a critical role in regulating neurotransmitter release from sympathetic nerves and neurons in the central nervous system, Intuniv works by strengthening the regulation of attention and behaviour by the brain's prefrontal cortex. Because Intuniv is a nonstimulant drug, it alleviates the risk of addiction associated with other ADHD drugs.
KANUMA
Kanuma (sebelipase alfa) is a first-in-class recombinant human lysosomal acid lipase for liposomal acid lipase deficiency (LAL-D), a genetic and progressive ultra-rare metabolic disease associated with multi-organ damage in infant, paediatric and adult patients, and premature death in infants. LAL-D patients have genetic mutations that result in decreased or lost activity of the LAL enzyme, which leads to an accumulation of cholesteryl esters and triglycerides in the liver, blood vessel walls, and other tissues. Kanuma provides a recombinant form of the human lysosomal acid lipase (rhLAL) protein that functions in place of the absent or abnormal LAL protein.
REVESTIVE
Revestive (teduglutide) is a first-in-class medicine for the management of Short Bowel Syndrome (SBS) in adults. SBS is a malabsorption disorder caused by the lack of a functional small intestine, often due to surgical removal, which is most often required due to Crohn's disease or small intestine tumours. The naturally-occurring human glucagon-like peptide-2 (GLP-2) hormone plays a key role in maintaining the normal structure and function of the small intestine. Revestive is a GLP-2 analogue differing from natural GLP-2 by a single amino acid and treats SBS by promoting mucosal growth, increasing intestinal blood flow, and restoring gastric emptying and secretion.
SPINRAZA
Spinraza (nusinersen) is an antisense oligonucleotide for the treatment of 5q spinal muscular atrophy (SMA), which is a serious, debilitating, life-threatening, autosomal recessive neuromuscular disease. Until now, sufferers of SMA had few options, and babies with the most severe form of the genetic disease, SMA1, deteriorated until they couldn't swallow and breathe, usually by nine months of age. Spinraza works by causing the body to increase production of the survival motor neuron protein, which is critical to the function of muscles. It has been shown to extend and improve the life of babies with SMA1, which is the most common genetic cause of death in children under two years of age.
TECENTRIQ
Tecentriq (atezolizumab) is a human monoclonal antibody approved for use in non-small cell lung cancer. It is the first approved cancer immunotherapy against the programmed cell death-ligand 1 (PD-L1) protein and works by blocking the interaction of PD-L1 with the programmed cell death protein 1 (PD-1), which is highly expressed on tumour cells. By blocking this interaction, the body's normal immune response is restored, and immune cells are now able to recognise and attack the cancer.
TRUMENBA
Trumenba is the second meningococcal B vaccine approved for use in Australia. Meningococcal vaccines are used to prevent infection by Neisseria meningitides, which causes meningitis and other forms of meningococcal disease. Six Neisseria meningitidis serogroups - A, B, C, Y, W-135 and X - are responsible for virtually all cases of the disease in humans, with vaccines against serotype B having proven the most difficult to produce. Trumenba is approved for use in individuals 10 years and older and is composed of two recombinant lipidated factor H binding proteins (fHBPs). Trumenba prevents serogroup B disease by inducing broadly protective bactericidal antibody responses against epidemiologically diverse serogroup B strains. fHBP is found on the surface of meningococcal bacteria and is essential for bacteria to avoid host immune defences.
VENCLEXTA
Venclexta (venetoclax) is a first-in-class treatment for patients with relapsed or refractory chronic lymphocytic leukaemia (CLL), a type of cancer of the blood and bone marrow. It is approved for use in patients who have a chromosomal abnormality called 17p deletion, which is detected using a diagnostic kit. Venclexta works by targeting a specific protein called Bcl-2. When normal cells become damaged, the body tells them to self-destruct, a natural process called apoptosis. In CLL patients, Bcl-2 builds up and prevents cancer cells from undergoing this programmed cell death. By targeting Bcl-2, Venclexta restores the process of apoptosis, and allows abnormal cancer cells to naturally self‑destruct.
Some new or extended uses for existing medicines
In addition the approval of new prescription medicines, patients will also benefit from the approval of new or extended therapeutic uses for existing medicines. For full information on the approved indications, please consult the ARTG.
ACTEMRA
Actemra (tocilizumab) was registered in 2009 for the treatment of rheumatoid arthritis in adults and later for juvenile idiopathic arthritis in children.
Actemra is now also indicated for the treatment of giant cell arteritis in adults.
JARDIANCE
Jardiance (empagliflozin) was registered in 2014 for the treatment of type 2 diabetes.
Jardiance is now also indicated to reduce the risk of cardiovascular death.
KEYTRUDA
Keytruda (pembrolizumab) was registered in 2016 for the treatment of metastatic melanoma.
Keytruda is now also indicated for metastatic non-small cell lung carcinoma, head and neck squamous cell carcinoma, and classical Hodgkin Lymphoma.
OPDIVO
Opdivo (nivolumab) was registered in 2016 for the treatment of metastatic melanoma and non‑small cell lung cancer.
Opdivo is now also indicated for the treatment of head and neck squamous cell carcinoma and classical Hodgkin Lymphoma.
PEDEA
Ibuprofen was first marketed in Australia in 1969 and is used for temporary pain relief.
Pedea is a new ibuprofen formulation for the treatment of haemodynamically significant patent ductus arteriosus in pre-term newborn infants less than 34 weeks of gestational age.
STELARA
Stelara (ustekinumab) was registered in 2009 for the treatment of plaque psoriasis, and later approved for psoriatic arthritis in 2015.
Stelara is now also indicated for the treatment for Crohn's disease.
XALKORI
Xalkori (crizotinib) was registered in 2014 for the treatment of ALK-positive advanced non-small cell lung cancer.
Xalkori is now also indicated for patients with ROS1 non-small cell lung cancer.
Priority determinations and orphan drug designations
In 2017, the Government established a new Priority review pathway aimed at providing the expedited assessment of major therapeutic advances treating serious or life-threatening medical conditions. At the same time, the existing orphan drug program was reformed to create a fairer system that aligns more closely with international criteria but without impacting the availability of drugs for rare diseases.
Note that Priority determinations and orphan drug designations do not mean approvals; they merely reflect how the submission will be evaluated. Incentives for these submissions are: a 3-month shorter target timeframe for Priority review; and fees waived for orphan drugs.
Priority determinations
The Priority determination process considers whether a prescription medicine is eligible for the Priority review pathway and is the first step towards expedited registration on the ARTG. Approved Priority determinations from 1 July 2017 are available at: Designation notices.
Orphan drug designations (from 1 July)
For full information on approved orphan drug designations from 1 July 2017, please consult: Designation notices
Orphan drug designations prior to 1 July 2017 are available at: Orphan drug designation prior to 1 July 2017
Biologicals
The Biologicals Regulatory Framework provides a comprehensive system of assessment and controls before products are allowed to be marketed in Australia, and also after registration approval through post-market vigilance.
For higher risk biologicals such as cell therapies, TGA evaluates their compliance with relevant standards relating to their quality, safety and efficacy.
For lower risk biologicals that have undergone no or only simple processing (called 'minimal manipulation'), such as products supplied by tissue banks, TGA evaluates their compliance with relevant quality standards.
All manufacturers of biologicals must also show that they comply with the manufacturing principles outlined in the Australian Code of Good Manufacturing Practice (GMP) for human blood and tissues.
Innovative and 'first-in-class' new biologicals registrations
Please note that the indication for which each biological is approved may be more specific than as described in general terms in this summary. For the full approved indications, please consult the ARTG.
ORTHO-ACI
Orthocell Pty Ltd
Ortho-ACI is a suspension of cultured autologous chondrocytes. The chondrocytes are derived from a biopsy of the patient's cartilage and are expanded using in vitro cell culture. Ortho-ACI is indicated for use in treatment of cartilage lesions associated with the knee, patella and ankle in patients with cartilage damage caused by trauma, wear or degradation including cartilage lesions associated with chondromalacia patella or osteochondritis.
Evaluation commenced: 16 January 2014 Registration decision: 26 May 2017
Some new or extended uses for existing biologicals
In addition to the approval of new biologicals, patients will also benefit from the approval of existing biologicals for new or extended therapeutic uses. For the full approved indications, please consult the ARTG.
OCULAR TISSUE
Queensland Eye Bank
Approval was granted for 'Cornea, normothermic storage - L' for cornea allograft. This approval allows the sponsor to use an alternative organ culture system at physiological temperatures, which extends the storage and shelf life of the donated tissue. This tissue is intended for the treatment of ophthalmic disorder, disease or trauma.
Evaluation commenced: 20 April 2017 Registration decision: 18 October 2017
MUSCULOSKELETAL TISSUE
Australian Biotechnologies Pty Ltd
Approval was granted for new forms of bone allograft tissue including demineralised cortical fibres and malleable bone segments. These allografts have been demineralised through acid treatment to enhance malleability and are intended for restoring bone volume or filling voids or gaps in the skeletal system.
Evaluation commenced: 22 February 2017 Registration decision: 30 June 2017
New registrations by therapeutic area
Antineoplastic and haematological agents
ADYNOVATE rurioctocog alfa pegol (antihaemophilic factor VIII Recombinant Coagulation Factor VIII rch)
AFSTYLA lonoctocog alfa (recombinant single-chain coagulation factor VIII)
ALECENSA alectinib
DARZALEX / JANSSEN DARATUMUMAB daratumumab
IBRANCE palbociclib
KISQALI ribociclib (as succinate)
LONSURF / ORCANTAS trifluridine / tipiracil hydrochloride
MONOFER ferric derisomaltose
ONCASPAR pegaspargase
TECENTRIQ atezolizumab (rch)
VENCLEXTA venetoclax
Cardiovascular, gastrointestinal & reproductive agents
MONUROL fosfomycin trometamol
RANEXA ranolazine
REKOVELLE follitropin delta (rhu)
REVESTIVE teduglutide
UROREC silodosin
Neurological & neuromuscular agents
INTUNIV guanfacine (as hydrochloride)
OCREVUS ocrelizumab
REXULTI brexipiprazole
SPINRAZA nusinersen (as heptadecasodium)
Endocrine, metabolic & respiratory agents
CINQAIR / CINQAERO reslizumab
GALAFOLD migalastat (as hydrochloride)
KANUMA sebelipase alfa rce
PHEBURANE sodium phenylbutyrate
RYZODEG 70/30 FLEXTOUCH and RYZODEG 70/30 PENFILL 70% insulin degludec (rys) / 30% insulin aspart (rys)
TRESIBA FLEXTOUCH and TRESIBA PENFILL insulin degludec (rys)
VELTASSA patiromer sorbitex calcium
ZEMAIRA human alpha-1-proteinase inhibitor
Vaccines, anti-infectives & allergen immunotherapies
DENGVAXIA Dengue tetravalent vaccinelive, attenuated
FLUZONE HIGH-DOSE inactivated trivalent influenza vaccine (Split Virion)
GRAZAX standardised allergen extract of grass pollen from Timothy grass (Phleum pratense)
INFLUVAC TETRA influenza virus haemagglutinin vaccine
TRUMENBA meningococcal group B vaccine
ZINPLAVA bezlotoxumab
Registrations of new prescription medicines
Once an application has been accepted for evaluation by TGA, the approval time is defined as the number of TGA working days between commencement of evaluation and registration decision. This timeframe is underpinned by legislation (see Therapeutic Goods Regulations 1990) and excludes public holidays, weekends, the time allocated to the sponsor to respond to requests for information, 'mutual clock stop' periods agreed with the sponsor, or other review activities.
All products were approved within the statutory 255 working day period.
Registrations of new or extended uses, or new combinations, of already-approved prescription medicines
Once an application has been accepted for evaluation by TGA, the approval time is defined as the number of TGA working days between commencement of evaluation and registration decision. This timeframe is underpinned by legislation (see Therapeutic Goods Regulations 1990) and excludes public holidays, weekends, the time allocated to the sponsor to respond to requests for information, 'mutual clock stop' periods agreed with the sponsor, or other review activities.
All products were approved within the statutory 255 working day period.
Generic prescription medicines
A generic medicine is an additional brand of an existing medicine. It contains the same 'active ingredient' as the existing medicine; the 'active ingredient' is the chemical that is biologically active in the body and makes the medicine work. Active ingredients can be manufactured and sold by other sponsors once the patent for the existing brand medicine has expired.
Apart from containing the same active ingredient, generic medicines must also be 'bioequivalent'. This means that the same amount of active ingredient is absorbed by the body over the same period of time for the same dose of generic or existing medicine.
Generic prescription medicines meet the same standards of quality, safety and efficacy as the existing medicine. TGA continually monitors the safety of registered medicines once they become available on the Australian market.
Registrations of chemical entities: first generics
Of the 101 generic prescription medicines registered during 2017, 29 submissions resulted in the registration of the 'first generic' version that contains a particular active ingredient. The term 'first generic' is the first registration approval by TGA which permits a sponsor to market a generic drug product in Australia. First generics are significant because they create more affordable treatment options for patients - the listing of a first generic triggers a 16% price reduction under the Pharmaceutical Benefits Scheme (PBS).
Because the first generic version registered by TGA may not necessarily be the first that is PBS-listed, the PBS website should be consulted for further information.
2017 chronological summary
Once an application has been accepted for evaluation by TGA, the approval time is defined as the number of TGA working days between commencement of evaluation and registration decision. This timeframe is underpinned by legislation (see Therapeutic Goods Regulations 1990) and excludes public holidays, weekends, the time allocated to the sponsor to respond to requests for information, 'mutual clock stop' periods agreed with the sponsor, or other review activities.
All products were approved within the statutory 255 working day period.
The sponsor name reflects the information in the ARTG at the time of registration. As sponsors may change over time, please consult the ARTG for full information in relation to these products, including full indications.
Registrations of chemical entities: other generics
The sponsor name reflects the information in the ARTG at the time of registration. As sponsors may change over time, please consult the ARTG for full information in relation to these products, including full indications.
Biosimilar prescription medicines
A biosimilar medicine is a version of a biological prescription medicine that is already registered and is referred to as the 'reference medicine'.
Both the biosimilar and its reference medicine will have similar core characteristics such as physicochemical, biological, immunological, efficacy and safety, which are demonstrated using comprehensive comparability studies. Most biosimilar medicines are likely to contain biotechnology-derived proteins as the active substance.
Please note that the indication for which each prescription medication is approved may be more specific than as described in general terms in this summary. For the full approved indications, please consult the ARTG.
Once an application has been accepted for evaluation by TGA, the approval time is defined as the number of TGA working days between commencement of evaluation and registration decision. This timeframe is underpinned by legislation (see Therapeutic Goods Regulations 1990) and excludes public holidays, weekends, the time allocated to the sponsor to respond to requests for information, 'mutual clock stop' periods agreed with the sponsor, or other review activities.
All products were approved within the statutory 255 working day period.
Australian Public Assessment Reports (AusPARs)
Each AusPAR outlines the outcome of TGA's pre-market registration process for prescription medicines - including new chemical/biological entities, extensions of indications, and generics - and provides a record of the scientific reasoning and risk-benefit considerations behind each regulatory decision.
In 2017, there were 69 AusPARs published. For full information on AusPARs, please see: Australian Public Assessment Reports for prescription medicines (AusPARs).