New Study Shows Superior Ability of PledOx to Reduce Chemotherapy Side Effects
December 27, 2012
PledPharma AB
Company Announcement
New Study Shows Superior Ability of PledOx to Reduce Chemotherapy Side Effects
Results of a preclinical study, comparing PledOx (calmangafodipir) - with the
clinically approved substance mangafodipir, are published in the latest number
of Translational Oncology. The results show that calmangafodipir has a
substantial and statistically significantly better protecting effect on
blood-forming bone marrow than mangafodipir, when used as an adjunct
(complement) to treatment with the chemotherapy drug oxaliplatin. Furthermore,
the results of the study show that the risk of brain uptake of potentially
harmful manganese is significantly less with PledOx, compared with
mangafodipir. Hence, PledOx may result in a more efficacious and less
troublesome chemotherapy.
Stockholm, 2012-12-27 12:16 CET (GLOBE NEWSWIRE) -- Colorectal cancer is the
third most common cancer-related cause of death in the Western world. A
standard treatment in this disease is oxaliplatin-based chemotherapy. However,
serious side effects in more than half of the patients lead to an intolerable
burden and cause dose reductions, delays, or, in worst-case scenarios, complete
discontinuation of the therapy. Chemotherapy exerts negative effects on
blood-forming bone marrow, which often leads to severe shortage of white blood
cells. The Swedish specialty pharmaceutical company PledPharma is developing
PledOx as a chemotherapy adjunct to reduce severe and dose-limiting side
effects.
- The chemotherapy drug oxaliplatin is widely used in colorectal cancer
treatment. It is a potent anti-cancer drug but suffers, like many other
chemotherapy drugs, from serious side effects. Hence, there is a great medical
need for an adjunct drug that can prevent serious side effects of oxaliplatin
and other chemotherapy drugs. The new study presented today shows that
calmangafodipir is significantly better to protect against serious side effects
than mangafodipir, which we evaluated in our first clinical study. Furthermore,
calmangafodipir has a better safety profile than mangafodipir. The results are
really promising, says Ursula Falkmer, Professor of Oncology at the University
Hospital in Aalborg, Denmark, and principal investigator of the first
controlled study with mangafodipir (2).
Improved protective effect
The two compounds studied can be used to protect bone marrow blood forming
cells against chemotherapy toxicity. Chemotherapy causes toxic effects on
blood-forming bone marrow and other normal cells by increasing the oxidative
stress (3). Mangafodipir reduces the harmful oxidative stress in healthy cells
by mimicking the body's own enzyme MnSOD. Both mangafodipir and MnSOD are
entirely dependent on the metal manganese to exert its cytoprotective effects.
In the body a large proportion of manganese is released from mangafodipir and
the substance therefore loses a significant portion of its cytoprotective
property. Release of manganese may also cause negative effects if the released
manganese is taken up into the brain. In calmangafodipir, which is a further
development of mangafodipir, 80% of the manganese has been replaced with
calcium, which in the study shows a significantly less manganese release,
superior ability to reduce chemotherapy-induced side effects and significantly
less manganese uptake into the brain (1).
- We are very pleased with the results of the study. This is a milestone in the
development of PledOx, which we hope will contribute to a more effective
treatment of many cancer patients in the future, says Jan Olof G. Karlsson,
founder of PledPharma and assistant Professor of Pharmacology at the Faculty of
medicine at the University of Linköping.
About PledOx
PledOx (calmangafodipir) is a further development of mangafodipir. Mangafodipir
is a contrast agent for MRI. The contrast effect is achieved by the released
manganese in the body, but the protection of healthy cells against chemotherapy
is achieved by manganese still bound to mangafodipir. Already during the
development of mangafodipir as a contrast agent, Jan Olof G. Karlsson, together
with PledPharma’s two other founders, Per Jynge and Rob Towart, realized that
the substance also protected against serious side effects of chemotherapy.
Since then several studies have been conducted which show that mangafodipir
protects normal cells against harmful side effects of chemotherapy
(1,2,4,5,6,7) without adversely affecting the anti-cancer effect. On the
contrary, it has been shown that mangafodipir enhances the anticancer
efficiency (4,6,7).
About the study
In the experimental study, "Superior Therapeutic Index of Calmangafodipir in
Comparison to Mangafodipir as a Chemotherapy Adjunct", calmangafodipir and
mangafodipir was compared with respect to their bone marrow protection when
treated with the cancer drug oxaliplatin. The results showed that, at
equivalent doses, calmangafodipir had a significantly better ability to protect
from myelosuppressive effect of the oxaliplatin. In addition, the study showed
that the uptake of manganese in the brain was significantly lower with
calmangafodipir than mangafodipir. The study also showed that calmangafodipir
increased the cancer inhibitory activity of oxaliplatin and also has an
anticancer activity of its own (1).
For further information please contact:
Jacques Näsström, CEO
+46 737 130979
Jacques.nasstrom@pledpharma.se
Jan Olof G Karlsson, Senior Scientist
+46 733 30 46 24
Janolof.karlsson@pledpharma.se
About PledPharma
PledPharma is a Swedish specialty pharma company that develops a new medicine,
PledOx™, for prevention of the severe side effects that patients develop as a
consequence of chemotherapy of cancer. Many times the treatment cannot be
carried out as planned due to severe side effects. The current market for
supportive cancer care is some SEK 72 billion. PledOx is a drug within the
patent protected substance class PLED, which protects the body’s normal cells
against oxidative stress. Oxidative stress is a condition where an
overabundance of harmful oxygen molecules (free oxygen radicals) has been
formed. We are also evaluating opportunities with PLED substances for other
diseases. PledPharma (STO:PLED) is listed on NASDAQ OMX First North. Erik
Penser is the Certified Adviser. For further information, please visit
www.pledpharma.se
References:
1. Karlsson JOG, Kurz T, Flechsig S, Näsström J, Andersson, RGG. Superior
therapeutic index of calmangafodipir in comparison to mangafodipir as a
chemotherapy adjunct. Transl Oncol. 2012;5:492-502.
2. Karlsson JOG, Adolfsson K, Thelin B, Jynge P, Andersson RGG, Falkmer UG.
First clinical experience with the MRI contrast agent and SOD mimetic
mangafodipir as an adjunct in cancer chemotherapy – a translational study.
Transl Oncol. 2012;5:32-38.
3. Doroshow JH. Redox modulation of chemotherapy-induced tumor cell killing
and normal tissue toxicity [editorial]. J Natl Cancer Inst.
2012;98:223-225.
4. Kurz T, Grant D, Andersson RGG, Towart R, De Cesare M, Karlsson JOG.
Effects of MnDPDP and ICRF-187 on doxorubicin-induced cardiotoxicity and
anticancer activity. Transl Oncol. 2012;5:252-259.
5. Yri OE, Vig J, Hegstad E, Hovde O, Pignon I, Jynge P. Mangafodipir as a
cytoprotective adjunct to chemotherapy--a case report. Acta Oncol
2009;48:633-635.
6. Laurent A, Nicco C, Chéreau C, Goulvestre C, Alexandre J, Alves A, Lévy E,
Goldwasser F, Panis Y, Soubrane O, Weill B, Batteux F. Controlling tumor
growth by modulating endogenous production of reactive oxygen species.
Cancer Res 2005;65:948-956.
7. Alexandre J, Nicco C, Chéreau C, Laurent A, Weill B, Goldwasser F, and
Batteux F (2006). Improvement of the therapeutic index of anticancer drugs
by the superoxide dismutase mimic mangafodipir. J Natl Cancer Inst 98,
236-244.
