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`POSTGnADUATR RxS'RARCR l.NSTITUTR OF $Cm.NCR, TRCBNOLOGY, ENVIRONMR.NT AND MRT>ICINR
`
`Li.wlL~ROI, Mnrch 2000,
`
`Dear Participants and Colleagues,
`Welcome to Cypms for the Millennium lOL" ICOC and Biomed Workshop (sponsored by the
`European Community, BIOMED, Grant B:tv1H4-CT97-2149), which are under the auspices of
`the Minister of Healtl1 and the Mayor of Limassol. Over 15 countries are represented and we
`hope that the sdentific presentations and discussions will stimulate our efforts to improve
`scientific knowledge and the treatment of thousands of patients , especially after the
`registration of Ll-Deferiprone in Europe, in addition to India. We are groteful to the
`Interoationa1 and Local Scientific Committees, Patients' Organisations and Sponsors for
`helping to make this conference a succcssf ul one. Selected abstracts will be published in
`Transfusion Science. We wish you a very pleasant stay in Limassol and hope to welcome you
`back to my birthplace in F1unagusta, when Cyprns is reunited.
`George J. l{ontoghiorghes
`Chai.nnan, ICOC Committee.
`
`Intcrrudional Scientific Committee:
`G. J. Kontoghiorghes (TCOC chairmen)
`J. 1. Mane (Biomed Meeting chaianan)
`MB. A{;arwal (Bombay, India)
`V. A. Berdouk.as (Sydney, Australia)
`R. W. Grady (New York, USA),
`H. V. Aposhia.n (Tuscon, USA).
`K.. N. Raymond (Berkeley, USA)
`C. K.attamis (Athens, Gree~e)
`S. Graphakos (Athens. Greece).
`L. Korlcina (Mos.cow, Russia),
`1 B. Afanasiev (Moscow, Russia),
`A Maggio (PaJenno, Italy),
`M. CappelHni (Milan, Italy),
`R.. Crichton (Louvain, Belgium),
`B.S. Van Asbeck (Utrecht, Netherlands),
`I. CaOO.ntchik (Jerusalem, Israel)
`E. Rachmilcwitz (Jerusalem, Israel).
`P. Nielsen (Hamburg, Germany)
`R.Vl.Evans (London,'UK)
`
`Spo:usors:
`Agios Therissos Medical Di.agnoi.1ic Centre ,
`NicosiJi, Cyprus.
`Cipla Ltd, Bombay, India.
`Vianex SA. , Athens, Greece.
`Medis s.r.1., Milan, ltaly.
`Apotex Inc., Toronto, Canada
`Duchefa Farma BV, Haarlem,
`The Netherlands.
`TIF, Nicosia. Cypms.
`BMG Lab Technologies, Jena., Germany.
`
`Local Scientific and Organisi.ne
`Committee:
`A. Papatryphonos (Makarios HospNicosia)
`F. Tsolakis (Limassol General Hospital)
`M. Angustiniotis (Makarios Hosp. Nkosia)
`N. Pavlides (Thal. Unit, Nicosia)
`A. Kolnagou (Thal. Unit, Paphos)
`M Hadjigavriel (Thal. Unit, Li.massol)
`M Sitarou (Thal. Unit Larnaca)
`I Pa.shalidis (Univ. Cypms, Nicosia)
`C. Alexandrou (Univ. Cyprus, Nicosia)
`K. Pattichis (Postgr. Res. Inst Limassol)
`S. Sophoclcous (Postgr. Res. Inst Lim~sol)
`G.Kontoghiorghes (Post.Res. Inst. Limassol)
`Organisations:
`Postgraduate Research Institute (PRD
`l Sabbagha., L. Antoniou, J. Economidou
`Thalassaemia Intemntional Federation
`P. Englezos, A. Ele.flheriou
`Thill119Saemia A ssocia.tion of Cyprus
`S. Minas, K. Fysentzou
`Antileukaemic Society of Cyprus
`A.Damianos
`~t Patients AssociatiQn
`A. Cluysostomou
`
`ICOC Committf}e
`G. J K.ontoghiorghes
`J.J.Marx
`V.Eybl
`C.Politis
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`/ ·
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`1 of 3
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`Taro Pharmaceuticals, Ltd.
`Exhibit 1025
`
`

`

`Millenium ICOC Limassol 22 to 26 March 2000
`
`. I
`
`j;, l l
`
`L 1-DEFERIPRONE WORLDWIDE UPDATE AN D NEW STRATEGIES FOR
`IMPROVING ITS THERAPEUTIC EFFICIENCY
`
`Kontoghiorghes 0 . J (1), Papatlyphonos A.(2) and Pashalidis 1. (1) Postgraduate Research
`Institute of Science, Technology, Environment and Medicine, Limassol (1) and Department
`ofHaematology, Makarios Hospital Nicosia. Cyprus(2)._ Tel: ++ 3575734615 Fax: ++
`e mall: prlgjk@cylink.com.cy
`3575395926
`
`L 1-Deferiprone has been registered in Europe last year, in addition to India, thus
`those who have
`it, especially
`the prospects of more patients using
`increasing
`complications with Desferal therapy or cannot afford its high price.
`
`However, commercial considerations and antagonism appear to still dominate the scene in
`the field of iron chelation. There are five companies selling L 1 and at least three
`companies selling desferrioxamine. The price of L 1 been sold in Europe is about the
`same as that of Desferal and there is a rush to find an alternative chelator as the patent of
`L 1 is about to end in 2003. Despite that the Desferal patent has ended several years ago,
`cheaper desferrioxamine has not reached the market because of fierce competition
`between phannaceutical companies.
`
`Over 6000 patients have been receiving L 1 Deferiprone in 40 countries since the first
`clinical trials back in 1987 [1,2}. Many patients in India, Switzerland and Cyprus have been
`taking L 1 daily since 1989. The number of patients using L 1 increases steadily worldwide.
`
`About 5% of the patients have been abandoning treatment with L 1 due to its toxic side
`effects or insufficient iron removal. Thalassaemia intermedia and other non heavily
`transfused patients easily reach negative iron balance at L 1 doses of about 75 mglkg.
`
`Similarly, combination therapy of LI and Desfem1 appear to be favored by some groups.
`
`The Toronto group's abandonment of L 1 because at 3x25 mg/kg/day was ineffective and
`may cause liver fibrosis [3] has not been confirmed by any other group especially in
`patients who have been taking L 1 daily for over 8-10 years at 75-120 mg/kg eg in the
`Swiss group or the Mumbai group (Tondury et at and Agarwal et al, 101
`h ICOC abstracts
`2000.
`
`It is interesting that a Swiss patient, who was taking LI secretly at 150 mg/kg for 2 years
`had a liver fibrosis score 0 (Tondury et al, 10th ICOC abstracts, 2000 and also a
`hypertransfused Cypriot patient, who was taking L 1 for 10 years and at 115 mg/kg for the
`last 2.5 years had no indications of liver damage.
`
`The rapid clearance of L 1 allows the use of repeated administration as previously
`described in the case of an inpatient (250 mg/kg/day) (5]. 75-120 mg/kg/day doses of L 1
`should be sufficient in most patients to cause a decrease within two years in serum ferritin
`and maintain it below 2.0 mgll. Despite that other factors such as dietary, metabolic and
`pharmacolkinetic should also be considered for improving the therapeutic profile of L 1, no
`such studies have yet been undertaken.
`
`page 11 of 15
`
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`2 of 3
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1025
`
`

`

`Millenium ICOC Limassol 22 to 26 March 2000
`
`L 1 is becoming a first line treatment for thousands of patients and there is a big scope for
`improving its therapeutic efficacy and minimizing its toxic side effects.
`
`References:
`1,2] Kontoghiorghes et al (1987) Lancet, i: 295-6 and (1987) British Moo. J. 295: 1509-12.
`3) Olivieri et al (1998) NEJM 339: 417-23.
`4] Tondury et al (1998) Br J. Haematol. 101 : 413-15.
`5] Kontoghiorghes et al (1990) Br.J.Haematol 76:295-300
`
`page 12 of15
`
`
`3 of 3
`
`Taro Pharmaceuticals, Ltd.
`Exhibit 1025
`
`