produced in a recombinant Chinese hamster
ovary (CHO) cell line. Because the glycosylation
pattern varies between ch14.18/CHO and ch14.18/
SP2/0 (Unituxin ® ) due to the different production
cell lines, which might influence pharmacokinetics,
efficacy and safety of the antibody, the two
products are not considered biosimilars. However,
no direct clinical comparison between the two
products has been conducted.
Dinutuximab beta was developed by the
Vienna-based biotech company, Apeiron Biologics
AG, as a result of a collaborative effort between
academic institutions (the SIOPEN group),
Austrian private investors, and public and private
research initiatives. EUSA Pharma (UK Limited)
acquired the exclusive global commercialisation
rights of dinutuximab beta from Apeiron
Biologics AG in September 2016. On 8 May 2017,
the European Commission granted marketing
authorisation for ‘dinutuximab beta Apeiron’.
The EMA evaluated the clinical efficacy of
dinutuximab beta in three studies: APN311-202;
302; and 303. Study 202 was a Phase I/II dose
schedule finding study of ch14.18/CHO
continuous infusion combined with subcutaneous
aldesleukin (IL-2) in patients with primary
refractory or relapsed neuroblastoma. Ch14.18/
CHO was administered as a ten-day continuous
infusion for a total of five cycles, combined with
IL-2 and 13-cis RA. A total of 44 patients from
Spain, France, Italy, UK, Germany, Israel, and
Austria with relapsed/refractory neuroblastoma
were enrolled. 18 At the end of treatment, response
was observed in 14/33 patients (42%) with
measurable disease. The treatment response was
11
HHE 2018 | hospitalhealthcare.com
higher in refractory disease (48%; 10/21) than
in relapsed disease (33%; 4/12) and the range for
the duration of response was from five weeks to
three years, median 2.3 years. Study 303 was
a ‘Retrospective analysis of data collected during
the administration of ch14.18/CHO continuous
infusion combined with subcutaneous aldesleukin
(IL-2) in patients with HR-NB under a
compassionate use program’. Ch14.18/CHO
was given in combination with fixed doses of
subcutaneous IL-2, and cis-retinoic acid. Between
November 2009 and August 2013, 54 patients
were treated. Half of the patients had relapsed
NB; 15 (28%) had refractory disease; and 9 (17%)
had received first-line neuroblastoma treatment
with either complete response or at MRD. At the
end of treatment (5–6 cycles) a response (CR+PR)
was observed in 12/39 patients (31%) with
evidence of disease at baseline while progression
occurred in 17/39 patients (44%). In patients with
relapse/refractory disease, the response rate was
10/36 (28%).
The 303 Study results were compared with
historical controls from a retrospective study
performed by Garaventa and colleagues of the
Italian Neuroblastoma Registry for patients
diagnosed during or after 1999, 24 because
treatment was deemed comparable to the
treatment used prior to immunotherapy in
patients included in study APN311-303.
Furthermore, comparison was restricted to
patients with relapsed neuroblastoma, patients
who were ≥1 year of age at initial diagnosis/
relapse and who presented with stage 4 at initial
diagnosis. The difference in OS between the two
cohorts was highly significant in favour of
dinutuximab beta. Finally, APN311-302 (or
HR-NBL-1/SIOPEN) evaluated safety and efficacy
of ch14.18/CHO from data collected in the high
risk neuroblastoma (HRNBL1) study of SIOP-
Europe (SIOPEN), a multinational, open-label,
randomised, controlled Phase III trial in HR-NB
patients conducted by SIOPEN to control minimal
residual disease after induction chemotherapy,
myeloablative therapy with stem-cell rescue, and
radiation therapy. Study APN311-302 evaluated
the effect of IL-2 to the ch14