Source : 'Generics Bulletin'
Fresenius Kabi AG has announced progress in the development of its proposed biosimilar to Roche’s Actemra/Ro-Actemra (tocilizumab) anti-inflammatory treatment.
The German firm’s MSB11456 tocilizumab candidate – which it obtained through its September 2017 acquisition of Merck KGaA’s biosimilars business – “successfully met its primary and secondary endpoints in two consecutively conducted [Phase I] clinical trials,” Fresenius announced.
Both subcutaneous and intravenous formulations of MSB11456 were tested in the two Phase I studies, “to capture the two different routes of administration to evaluate the tocilizumab biosimilar candidate’s bioequivalence, safety and immunogenicity, in comparison to its reference candidates.”
Noting that the first Phase I study was “a randomized, double-blind, parallel-group study to determine the pharmacokinetic, pharmacodynamic, safety, tolerability and immunogenicity of MSB11456 following a single subcutaneous injection in healthy subjects,” Fresenius said this study “met all primary and secondary endpoints,” with pharmacokinetic equivalence of MSB11456 to both the US and EU reference products successfully demonstrated.
“The clinical trial also confirmed the similarity of MSB11456 and the US reference product and the EU reference medicinal product at pharmacodynamic level,” Fresenius reported, “and no noteworthy differences in safety and immunogenicity were observed across the three treatment groups.”
Meanwhile, the second and more recent Phase I study was also a randomized, double-blind, parallel-group study “to evaluate the pharmacokinetic, safety, immunogenicity and tolerability of MSB11456 versus the US reference product after a single intravenous infusion in healthy volunteers.” Meeting all primary and secondary endpoints, the study successfully demonstrated pharmacokinetic equivalence, again with “no noteworthy differences in safety and immunogenicity observed across the two treatment groups.”
“The subcutaneous form may turn out to be the more meaningful market segment for us as we are currently assuming to lead the biosimilar competition.”
Michael Schönhofen, member of Fresenius Kabi’s management board and president of the pharmaceuticals and devices division, said the two successful trial outcomes “represent an important milestone in our commitment to provide high-quality and affordable biosimilar products to more healthcare providers and patients around the world.”
He added that the firm would “continue to expand our biosimilar portfolio to provide affordable alternative solutions for people living with autoimmune diseases.”
Fresenius’s MSB11456 candidate is currently in Phase III development, with an estimated primary completion date of 24 September 2021 and study completion date of 13 July 2022. The global study – which aims to compare the efficacy, safety, tolerability and immunogenicity of the tocilizumab biosimilar with the EU reference product in patients with moderately to severely active rheumatoid arthritis – has already completed the enrolment of patients from several countries across Europe.
Providing a detailed look at Fresenius Kabi’s biosimilars pipeline and ambitions for its existing portfolio, the Fresenius group’s president, CEO and chairman, Stephan Sturm, recently confirmed that Kabi still expected to enter the US and EU markets in 2023 with its tocilizumab biosimilar in “both dosage forms, subcutaneous and intravenous.”
“The subcutaneous form may turn out to be the more meaningful market segment for us as we are currently assuming to lead the biosimilar competition,” he noted. ("Fresenius Kabi Awaits EMA Inspection For Pegfilgrastim Biosimilar" "Generics Bulletin" )
With Roche reporting Actemra/RoActemra sales that were up by almost a third to CHF2.9bn ($3.2bn) in 2020, along with additional interest in the product as a treatment for COVID-19, the brand offers a significant target for biosimilars developers.
Biogen and China’s Bio-Thera Solutions recently celebrated positive results from a Phase III trial for their BAT1806 proposed tocilizumab biosimilar, with the candidate meeting primary endpoints and showing “equivalent efficacy and comparable safety profile” in patients with moderate-to-severe rheumatoid arthritis inadequately controlled by methotrexate therapy. ("Biogen and Bio-Thera Reveal Tocilizumab Progress" "Generics Bulletin" )
Gedeon Richter is also among players developing a biosimilar Actemra/RoActemra product after striking a $16.5m deal in April 2020 with Taiwanese biotech firm Mycenax to gain global development, manufacturing and commercialization rights to the company’s tocilizumab candidate. ("Gedeon Richter Strikes 165m Global Tocilizumab Deal" "Generics Bulletin" ) Earlier in 2021, the Hungarian firm confirmed that clinical trials for the biosimilar, as well as its Prolia/Xgeva (denosumab) candidate, would begin “this year.”
Tocilizumab has gained fresh prominence in the context of the COVID-19 pandemic, with the intravenous formulation of Actemra receiving an emergency use authorization from the US Food and Drug Administration for treating the inflammatory response associated with severe COVID-19 symptoms. This has led to shortages of the product, with Roche’s Genentech division acknowledging the likelihood of variable availability and intermittent stockouts. ("COVID-19-Induced Actemra Shortage Causes Headaches For CAR-T Centers" "Scrip" )
The European Medicines Agency has also warned of shortages of RoActemra in EU member states because of the growing demand for the product “which outweighs current production capacities.” ("Coronavirus Notebook New Deal To Boost Local Vaccine Manufacturing EU Warns Of RoActemra Shortages" "Pink Sheet" )
Earlier in the year, Roche pledged not to enforce intellectual property covering tocilizumab in low- and middle-income countries during the pandemic. ("Roche Tocilizumab IP Relaxation Does Not Go Far Enough" "Generics Bulletin" )
However, humanitarian organization Médecins Sans Frontières urged the brand company to go further and extend its non-enforcement promise to all countries, beyond just LMICs; to disclose details of secondary patents and pending patent applications and withdraw them; and to share cell lines and manufacturing information with other producers so that they can scale up biosimilar production.
Recently, Hetero’s Tocira 400mg/20ml biosimilar version of tocilizumab received an Emergency Use Authorization from the Drug Controller General of India allowing its use to treat COVID-19 in hospitalized adults who are receiving systemic corticosteroids and require supplemental oxygen, non- invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation.
The product – which is manufactured by Hetero’s biologics arm, Hetero Biopharma, at its dedicated Indian biologics facility in Jadcherla, Hyderabad – “will be available from September end,” the company indicated.
Hetero group chairman B Partha Saradhi Reddy said the approval “demonstrates our technical capabilities and commitment to bringing important therapeutics relevant to COVID care.”
“This approval is extremely crucial for supply security in India considering a global shortage of tociluzumab,” Reddy underlined, adding that the firm “will be working closely with the government to ensure equitable distribution.”
By David Wallace