Belinostat has favorable safety profile in PTCL BELIEF study

1/24/2013 4:13 PM EST

Topotarget
Company Announcement

Belinostat has favorable safety profile in PTCL BELIEF study

To NASDAQ OMX Copenhagen A/S
Announcement No. 01-13 / Copenhagen, January 24, 2013

Topotarget A/S (NASDAQ OMX: TOPO) announces that clinical data on belinostat
are presented at the 5th Annual T-Cell Lymphoma Forum on January 24-26, 2013,
in San Francisco, USA. 

The abstract presents the preliminary safety data from the pivotal phase II
BELIEF trial (CLN-19) of belinostat as a single agent in patients with relapsed
and/or refractory peripheral T-cell lymphoma (PTCL). It is concluded that
belinostat is well-tolerated with a favorable safety profile in patients with
PTCL and that belinostat is a candidate for a well-tolerated alternative for
the treatment of this disease. The poster is scheduled to be presented at the
conference on January 26, 2013. 

The abstract text is shown below:

Belinostat in relapsed and/or refractory peripheral T-cell lymphoma (R/R PTCL):
Preliminary safety results 

Authors: Owen O’Connor, Steve Horwitz, Tamas Masazi, Lauren Pinter-Brown,
Shanta Chawla, Andrei Shustov 

Background: The prognosis for patients with R/R PTCL remains poor. Romidepsin
and pralatrexate are approved in the US; with overall response rates (ORR) of
25% and 27% respectively1, 2. Pralatrexate, an anti folate, causes
myelosuppression and mucositis. Fatigue was prominent with romidepsin, an
HDACi. This class has been implicated in QTc prolongation. Belinostat, a novel
pan-HDACi, in preliminary study has similar ORR in R/R PTCL and is well
tolerated with common grade 1-2 toxicities, gastrointestinal and
constitutional3. These toxicities were not attenuated in combination studies4. 
BELIEF is the pivotal Ph 2 study that evaluated the safety and efficacy of
belinostat in R/R PTCL. We present the preliminary safety data from the BELIEF
study. 

Methods: BELIEF is an open-label, multicenter, single-arm efficacy and safety
study in patients with R/R PTCL after failure of at least one prior systemic
therapy. PTCL diagnosis was confirmed by central pathology review. EKGs were
centrally reviewed. Major inclusion criteria were: platelet counts = 50,000/µL,
no prior HDACi therapy, measurable disease and adequate organ function.
Belinostat was given as a 30 min IV infusion at 1000 mg/m2 on days 1–5 of a 3
week cycle until disease progression or unacceptable toxicity. The primary
endpoint was ORR. Safety was monitored through 30 days from the last dose of
belinostat. Efficacy determinations are ongoing. 

Results: Total of 129 patients, 53% men, median age 63 yr (range 29–81 yr) were
treated. The median number of cycles was 2 (range 1–31). One dose reduction
occurred in 11% of patients and 1% had two dose reductions. AEs resulted in
dose delays in 21% of patients, and 18% discontinued for AEs, including death.
Grade 3/4 non hematologic AEs observed in >3% of patients included
asthenia/fatigue 9%, pneumonia 7%, dyspnea 6%, infection 4%, febrile
neutropenia 4%, pruritus 3%, deep vein thrombosis 3%, and hypotension 3%. Grade
3 QTc prolongation was reported in 2% of patients. Grade 3/4 hematologic
toxicities were: thrombocytopenia 6% in patients with platelet counts of
=100,000, anemia, leukopenia and neutropenia each 13%. A total of 23 patients
(18%) died on treatment or within 30 days of last dose, predominantly due to
PTCL progression. No death was attributed to belinostat. 

Conclusions: Belinostat is well tolerated with a favorable safety profile in
patients with R/R PTCL. Based on efficacy in the earlier Ph 2 study and safety
in the BELIEF trial, belinostat is a putative well-tolerated option for the
treatment of PTCL. Other studies show that full doses of belinostat can be
combined with other cytotoxic regimens making combination therapy for patients
with PTCL feasible. 

Topotarget A/S

For further information, please contact:

Anders Vadsholt, CEO: Direct: +45 39178345

Background information

About Topotarget
Topotarget (NASDAQ OMX: TOPO) is an international biopharmaceutical company
headquartered in Copenhagen, Denmark, dedicated to clinical development and
registration of oncology products. In collaboration with Spectrum
Pharmaceuticals, Inc., Topotarget focuses on the development of its lead drug
candidate, belinostat, which has shown positive results in the treatment of 
hematological malignancies and solid tumors, obtained by both mono- and
combination therapy. For more information, please refer to www.topotarget.com. 

About belinostat
Belinostat is a novel pan-HDAC inhibitor in late-stage clinical development
with more than 1,000 patients treated. Belinostat has a promising safety
profile which allows combination with traditional chemotherapy. Preclinical
experiments demonstrated belinostat to be effective against multiple cancers by
inhibiting cell proliferation and inducing programed cell death (apoptosis) in
tumor cells. Belinostat has been tested in a number of phase I/II clinical
trials in hematological cancers and solid tumors both in mono- and combination
therapy. Data from these trials have provided evidence of the anti-tumor effect
of belinostat, including as monotherapy in PTCL and cutaneous T-cell lymphoma
(CTCL), liver cancer, and thymoma. 

About the BELIEF trial
BELIEF is a pivotal, open-label, multi-center, single-arm efficacy and safety
trial of i.v. belinostat in patients with relapsed or refractory PTCL. FDA has
granted belinostat Orphan Drug and Fast Track designation for the treatment of
PTCL. The trial was initiated in December 2008 and recruitment was completed
with 129 patients in September 2011. In total, the study included approximately
100 clinical centers globally. 

Topotarget Safe Harbor Statement
This announcement may contain forward-looking statements, including statements
about Topotarget A/S’ expectations to the progression of Topotarget A/S’
clinical pipeline and with respect to cash burn guidance. Such statements are
subject to risks and uncertainties of which many are outside the control of
Topotarget A/S, and which could cause actual results to differ materially from
those described. Topotarget A/S disclaims any intention or obligation to update
or revise any forward-looking statements, whether as a result of new
information, future events, or otherwise, unless required by Danish law.