DEFERIPRONE (Keifer)
`A report of 22 patients who have taken it for over a decade
`
`M.B. Agarwal, G. Rajadhyaksha, Sameer Munot
`Department of Haematology,
`LTMG Hospital & L1M Medical College, Mumbai - 400 022. India.
`
`Since 1989, 216 transfusion dependent thalassaemia major patients have
`received Deferiprone (Ll, Kelfer) as an iron chelator in Mumbai (India).
`Fifty two of these, had started Deferiprone way back in 1989 when the
`initial phase-II/III trial of L1 began in India. The initial results were
`published in 1992 in British Journal of Haematology. Twenty two .of these
`have continued to take Deferiprone until now except for a brief period in
`1994-95, when the clinical trials were over and the drug was yet not
`licensed for marketing (approximately 16 months). These patients are
`regularly monitored for efficacy and adverse effects, if any, of Deferiprone
`for over a decade. Hence, they form a group of probably, longest, "almost
`continuous" use of Deferiprone in transfusion dependent thalassaemia. The
`dose varied between 75 and 120 mg/kg/day with a mean of 86±12 mg/kg/day.
`The efficacy was excellent with S. ferritin dropping from a mean of 5820 ±
`2660 ng/ml to 2130 ± 1680 ng/ml. Nine of these 22 patients (40%) have had
`their S. ferritin below 2000 ng/ml for last 4 years or more. Eleven of these
`patients have entered the third decade of life. Assessment of cardiac
`function shows normal ejection fraction in all with mild diastolic
`dysfunction in two. One of them has overt diabetes while 2 have altered GIT.
`Seven out of eleven girls have achieved menarche and 3 have regular menses.
`No one has hypothyroidism or hypocalcemia. LFT shows mild alternations in
`liver enzymes in majority of them. Three are HCV-RNA positive and two of
`them have received Interferon+ Ribavarin therapy. Four have complained of
`occasional GI symptoms, one had transient leukopenia while one had skin
`changes suggestive of zinc deficiency. Vague skeleto-muscular pain have
`occurred in six patients while frank arthralgia occurred in three patients.
`None required discontinuation of the therapy. Three of these patients have
`had sequential liver biopsies during last 3 years (2'biopsies i~ 2 patients
`and 3 biopsies in one patient). None of them have shown progressive fibrosis
`I cirrhosis. There have been no toxicities related to visual and auditory
`system. There is no evidence of immune paralysis, opportunistic infections
`or immune complex disorders except variable sero positivity for ANA, RA,
`single standed ds-DNA antibodies and Anti-histone antibody.
`We conclude that very Jong-term use of Deferiprone during second and third
`decade of life in a cohort of patients who tolerated it well, has been a reasonably
`effective therapy without occurrence of known or unknown toxicities. This is
`probably the "Jarg9.st ~nd th~ longest" use of Deferiprone in a given set of patients of
`..
`transfusion dependent' thai~§.._aemia .
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`1 of 2
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`Taro Pharmaceuticals, Ltd.
`Exhibit 1011
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`Millennium ICOC
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`10th International Conference on Oral Chelators
`in the Treatment of Thalassaemia and Other Diseases
`and Biomed Meeting
`22-26 March 2000 I"· ~~
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`Limassol, ~¥Prus
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`2 of 2
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`Taro Pharmaceuticals, Ltd.
`Exhibit 1011
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