Biosimilars

Comparable efficacy and safety observed in patients switched to biosimilar CT-P10

Rituximab is a monoclonal antibody that targets the CD20 protein that is primarily found on B lymphocytes. Through depletion of CD20-positive B cells in the peripheral blood and bone marrow, rituximab is effective for treating some haematological malignancies and immune-mediated diseases such as rheumatoid arthritis (RA). CT-P10 (Truxima) is a biosimilar of the rituximab reference product. It is the first biosimilar to receive market authorization from the European Medicines Agency and is approved in Europe for all indications for which RTX is licensed [1]. A phase I randomized controlled trial (RCT) in patients with RA demonstrated pharmacokinetic equivalence of CT-P10 and reference rituximab over 24 weeks of treatment [2], and comparable efficacy and safety of these two drugs has recently been demonstrated over an extended treatment duration from the same trial [3]. With biosimilars typically being less expensive than originator biologicals [4], it is of interest to know whether patients treated with an originator biological can be switched to a biosimilar to save healthcare costs and increase access without affecting treatment efficacy or safety. An open-label extension (OLE) study that enrolled patients who had completed the aforementioned phase I RCT has been published [5]. The study has demonstrated comparable efficacy and safety profiles in patients who switched from the reference rituximab to CT-P10 and those maintained on CT-P10 throughout treatment [5].

Second etanercept biosimilar approved in Canada

Sandoz, the generics division of Novartis, announced on 21 August 2017 that its etanercept biosimilar, Erelzi, is now available in Canada.

Biosimilars applications under review by EMA – August 2017

The European Medicines Agency (EMA) is the body responsible for approval of biosimilars within the European Union (EU). A legal framework for approving biosimilars was established in 2003. Approval of biosimilars is based on an abbreviated registration process, which allows biosimilars manufacturers to provide a reduced package of information compared to originator drugs, provided they can prove ‘similarity’ to the originator or reference drug.

WHO launches consultation on prequalification of biosimilars

The World Health Organization (WHO) announced in September 2017 that it would be launching its pilot project for prequalifying biosimilars in October 2017. The step is intended to make ‘some of the most expensive treatments for cancer more widely available in low- and middle-income countries’.

Sanofi receives tentative FDA approval for insulin lispro biosimilar

Pharma giant Sanofi announced on 1 September 2017 that it had received tentative approval for Admelog, its insulin lispro biosimilar, from the US Food and Drug Administration (FDA).

Positive phase III results for Amgen’s trastuzumab biosimilar

Biotech giant Amgen and partner Allergan announced on 9 September 2017 positive data from a phase III study of their trastuzumab biosimilar (ABP 980) compared to Herceptin (trastuzumab).

Positive phase I results for rituximab biosimilar CT-P10 in patients with rheumatoid arthritis

Rituximab is an established anti-CD20 monoclonal antibody used for the treatment of some haematological cancers and immune-mediated diseases, such as rheumatoid arthritis (RA). CT-P10 (Truxima) is the first biosimilar of the rituximab reference product and was approved in Europe for all licensed RTX indications in February 2017 [1]. A phase I randomized controlled trial (RCT) of CT-P10 versus reference rituximab in patients with active RA demonstrated that the two drugs had equivalent pharmacokinetics after a single course of treatment and that their efficacy, pharmacodynamics, immunogenicity and safety were comparable up to Week 24 [2]. To allow comparison of CT-P10 versus reference rituximab, patients in the same phase I trial received a second course of treatment and were evaluated for efficacy, safety, pharmacokinetics, pharmacodynamics, and other clinical data for up to 72 weeks. These data demonstrate that the clinical profile of CT-P10 is comparable to reference rituximab in patients with RA over an extended treatment duration [3].

Two trastuzumab biosimilars submitted to FDA

Two different groups announced that their trastuzumab biosimilars had been successfully submitted to the US Food and Drug Adminstration (FDA) for review.

Strategies of players on the global biopharmaceutical market

With many expensive and high-selling biologicals losing patent protection and other exclusivity rights, biosimilars of these molecules may now enter the market, resulting in a shift of market shares, revision of strategies of companies and attraction of new players to the biopharmaceutical market.

EC approval for three rituximab biosimilars

On 13 July 2017, three rituximab biosimilars, Blizima, Rituzena (previously Tuxella) and Ritemvia, received European Commission (EC) approval.

Boehringer Ingelheim starts phase III interchangeability trial for adalimumab biosimilar

Germany-based Boehringer Ingelheim Pharmaceuticals (Boehringer Ingelheim) announced on 27 July 2017 that the first patient had been enrolled into the phase III VOLTAIRE‑X interchangeability study of its adalimumab biosimilar (BI 695501). The company says the trial ‘is the first study in the US to investigate an interchangeability designation for an adalimumab biosimilar candidate’.

Biological drug evolution: improved awareness and pharmacovigilance required

The safety profile of established biological drugs can alter over time following changes to manufacturing processes. However, healthcare professionals are often unaware of changes and there is a need for improved pharmacovigilance, according to a report published by researchers in Scotland, UK [1].

FDA approves adalimumab biosimilar Cyltezo

On 25 August 2017, the US Food and Drug Administration (FDA) approved its second biosimilar version of AbbVie’s Humira (adalimumab).

Australia’s TGA consults on naming of biologicals

Australia’s drug regulatory agency, the Therapeutic Goods Administration (TGA), announced on 28 July 2017 that it was opening a consultation on how to name biologicals.

Rituximab biosimilar CT-P10 could save Europe Euros 90 million in its first year

A recent publication in Advances in Therapy suggests that introducing CT-P10, a biosimilar of the anti-CD20 monoclonal antibody rituximab, would generate significant savings for European healthcare systems [1]. CT-P10 is approved by the European Medicines Agency (EMA) for all indications held by reference rituximab, including rheumatoid arthritis and haematological cancers, such as non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia. Although the therapeutic benefits of anti-CD20 therapy are well established, the cost of reference rituximab is thought to create barriers to patient access [2]. It is hoped that the introduction of more affordable biosimilars will help address this issue. Gulácsi L et al. therefore quantified the potential budgetary impact of introducing CT-P10 for the treatment of rheumatoid arthritis and CD20-positive cancers in 28 European countries [1].

Biological drug evolution: inadequate short-term clinical trials

The safety profile of established biological drugs can alter over time following changes to manufacturing processes and short-term clinical trials fail to isolate adverse events, according to a report published by researchers in Scotland, UK [1].

EC approval for adalimumab biosimilar Imraldi

Samsung Bioepis announced on 25 August 2017 that it had received European Commission (EC) approval for its biosimilar adalimumab product Imraldi.

Barriers to the market access of biosimilar monoclonal antibodies

In September 2013, the first biosimilar monoclonal antibody (mAb) was approved by the European Medicines Agency (EMA), i.e. biosimilar infliximab (Inflectra/Remsima). These products entered the European market in 2015, after expiry of patent and other exclusivity rights of the innovator medicine Remicade. With the ever-increasing cost of health care and the economic pressure to reduce or sustain healthcare expenses, biosimilars could be instrumental in reducing cost for medication and increasing patient access to treatment. Although exclusivity rights of multiple mAbs are expired (rituximab in 2013, trastuzumab in 2014), only recently biosimilar mAbs other than infliximab are receiving marketing authorization (rituximab, adalimumab). Furthermore, earlier biosimilars have seen slow uptake in European markets. This may imply that several barriers hinder market access of biosimilar mAbs.

Adello Biologics starts phase I trial for pegfilgrastim biosimilar

US-based biosimilars specialist Adello Biologics has started a phase I clinical trial for a biosimilar version of Amgen’s Neulasta (pegfilgrastim).

Biosimilar pegfilgrastim highly similar to Neulasta

Canada-based Apobiologix published analytical results demonstrating the similarity of their pegfilgrastim product to the US reference product, Amgen’s Neulasta (pegfilgrastim) [1].

Biosimilars of insulin lispro

Last update: 26 January 2018

Insulin lispro is a fast acting insulin analogue used to treat people living with Type 1 or Type 2 diabetes. Insulin lispro has one primary advantage over regular insulin for postprandial glucose control. It has a shortened delay of onset, allowing slightly more flexibility than regular insulin, which requires a longer waiting period before starting a meal after injection. Both types should be used in combination with a longer acting insulin for good glycaemic control.

Real-life data supports efficacy and safety of biosimilar filgrastim

Biosimilars of filgrastim are widely used in the prophylaxis of chemotherapy‐induced (CIN) and febrile neutropenia (FN). However, there are limited observational data on the use of granulocyte colony-stimulating factor (G‐CSF) in non‐Hodgkin’s lymphoma (NHL) and its aggressive subtypes including diffuse large B‐cell lymphoma (DLBCL).

Biocad’s rituximab ‘similar biologic’ recommended for approval in India

Russian biotechnology company Biocad announced on 4 July 2017 that it would ‘soon’ receive marketing approval for its rituximab ‘similar biologic’ in India under the trade name Acellbia.

FDA accepts application for Celltrion/Teva’s rituximab biosimilar

South Korean biotechnology company Celltrion and partner Israeli generics giant Teva Pharmaceuticals (Teva) announced on 29 June 2017 that the regulatory submission for their proposed rituximab biosimilar (CT‑P10) had been accepted by the US Food and Drug Administration (FDA).

Biosimilar trastuzumab candidate shows ‘similarity’ to Herceptin

Results of a phase III clinical study of Celltrion’s biosimilar trastuzumab candidate CT‑P6 demonstrated the ‘similarity’ of the efficacy and safety compared to the originator biological (Herceptin) in patients with HER2+ breast cancer [1].

Setback in Biocon/Mylan’s biosimilar programme after GMP inspection

Biocon/Mylan’s biosimilar programme has hit a stumbling block after failing an inspection by the French inspecting authority (L’Agence nationale de sécurité du médicament et des produits de santé: ANSM).

US prescribers’ views on the naming and labelling of biologicals

The Alliance for Safe Biologic Medicines (ASBM) has published the results of a survey in which they asked 400 US physicians for their views on the labelling of biosimilar medicines, and a separate survey in which they asked another 400 US physicians for their views on the naming of biosimilar medicines [1]. All those surveyed were prescribers of biological medicines. The surveys were carried out in the run up to the release of guidance from the US Food and Drug Administration (FDA) on the non-proprietary naming of biological products.

Real world switching data for etanercept biosimilar Benepali

Real world evidence from a study of etanercept biosimilar Benepali (SB4) compared to Amgen/Pfizer’s arthritis blockbuster Enbrel (etanercept) have demonstrated ‘sustained efficacy and safety, and high acceptance and adherence in patients initiating treatment with Benepali (etanercept)’, according to Biogen.

FDA rejects Pfizer’s epoetin alfa biosimilar

US pharma giant Pfizer announced on 22 June 2017 that the US Food and Drug Administration (FDA) had rejected its application for approval of its epoetin alfa biosimilar.

Biocad registers rituximab similar biotherapeutic product in Bolivia and Honduras

Russian biotechnology company Biocad announced on 6 June 2017 that it had obtained a marketing authorization for its rituximab ‘similar biotherapeutic product’ in Bolivia and Honduras under the trade name Usmal.

Scientific rationale for extrapolation of cancer indications

Extrapolation involves extending and applying the data from clinical studies regarding one medical condition to another medical condition. Once biosimilarity has been proven, biosimilars can also be approved for one or more additional indications held by the reference product, without the need for clinical data in those indications. Author Michinori Ogura from the Tokai Central Hospital, Gifu, Japan and colleagues from France and South Korea investigated the scientific rationale for extrapolation using the rituximab biosimilar CT-P10 as an example [1].

EC approval for etanercept biosimilar Erelzi

Sandoz, the generics division of Novartis, announced on 27 June 2017 that it had received European Commission (EC) approval for its biosimilar etanercept product Erelzi.

FDA rejects pegfilgrastim biosimilar from Coherus

Coherus BioSciences (Coherus) announced on 12 June 2017 that it had received a complete response letter (CRL) from the US Food and Drug Administration (FDA) regarding its candidate pegfilgrastim biosimilar, CHS‑1701.

Pharmocovigilance of rituximab in Argentina

Novex is a rituximab medicamento biológico similar (similar biological medicines) approved in Argentina. According to Argentinian regulations such products need to implement an active pharmacovigilance programme. This requires regular reporting to the Argentinian regulatory agency Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (National Administration of Drugs, Foods and Medical Devices; ANMAT).

EMA approval for adalimumab biosimilar Imraldi

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) announced on 23 June 2017 that it had recommended granting marketing authorization for the adalimumab biosimilar Imraldi from Samsung Bioepis.

Trastuzumab biosimilar could reduce breast cancer treatment costs

Trastuzumab is a monoclonal antibody that interferes with the human epidermal growth factor receptor 2 (HER2)/neu receptor. In some cancers, notably certain types of breast cancer, HER2 is overexpressed, and causes cancer cells to reproduce uncontrollably. Trastuzumab is therefore used to treat certain breast cancers.

Adalimumab and infliximab biosimilars from Sandoz accepted for review by EMA

Sandoz, the generics division of Novartis, announced on 31 May 2017 that the regulatory submissions for its proposed adalimumab (GP2017) and infliximab (PF‑06438179) biosimilars had been accepted by the European Medicines Agency (EMA).

Biosimilars of pegaspargase

Pegaspargase is a modified enzyme. It is a form of L-asparaginase which has undergone PEGylation. It is used as an anticancer (‘antineoplastic’ or ‘cytotoxic’) chemotherapy drug. It is indicated for the treatment of acute lymphocytic leukaemia (ALL), non-Hodgkin’s lymphoma and for treatment of patients who have had a hypersensitivity reaction to another form of asparaginase.

Biosimilars and sustainability

Competition between brand-name biologicals and biosimilars has the potential to reduce future cancer costs, according to researchers from Italy [1].

EC approval for rituximab biosimilar Rixathon

Sandoz, the generics division of Novartis, announced on 19 June 2017 that it had received European Commission (EC) approval for its biosimilar rituximab product Rixathon.