tdr> Public/Private partnership - Visceral Leishmaniasis

[Jeffrey Shaw]

>Date: Thu, 28 Oct 1999 01:28:16 +0100 (MET)
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>Subject: tdr> Public/Private partnership - Visceral Leishmaniasis
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>PUBLIC/PRIVATE PARTNERSHIP: DEVELOPING AN ORAL TREATMENT FOR VISCERAL
>LEISHMANIASIS
>(from TDRnews Oct 1999)
>
>A boy whimpers as the doctor searches for the vein in his skinny arm, in
>which to insert the catheter. He knows what he's in for: six hours on a
>drip with shivering and fever. But it's worth it and he will tolerate
>it. Otherwise he will die.
>
>Twelve beds, each with a clean green sheet, are neatly arranged along
>the length of a ward, each with a plastic bottle of golden-coloured
>fluid suspended above, attached through a length of tube to the vein in
>a patient's arm. Twelve patients lie, stoically biding the month of
>treatment. There are children, men and women, old and young.
>
>A mass of patients crams a waiting room. Inside, more people. The doctor
>is well known and patients, from the poorest sectors of society, are
>referred to him from far away. A young child has received pentostam,
>first-line treatment for kala-azar. His buttocks, the site for injection
>of the drug, are sorely ulcerated. Is he one of the 40% who don't
>respond to this treatment any more?
>
>A boy's eyes are earnestly fixed on the doctor's face. The doctor
>pronounces him cured after six months of follow-up, and signs him off.
>The boy looks eager. Now he knows he will live, he is full of hope.
>
>A man with a walrus moustache listens intently to the doctor's careful
>explanation about the trial. He looks at the informed consent papers,
>now translated into Hindi on advice from the local ethics committee, and
>answers the doctor's questions. He knows he must receive treatment else
>he will die. Finally he decides to refer to his family members before
>consenting to enter the trial.
>
>In the laboratory where samples from the kala-azar patients are
>analysed, the equipment is arranged systematically around the room.
>There is a row of little tubes, each labelled clearly, the analyst
>methodically testing each in turn. He codes, and carefully wraps, each
>microscope slide made from samples taken from the patients' spleens. The
>up-to-date reference books lining the walls already wear an aged look.
>
>This is the setting for imminent Phase III clinical trials of a new oral
>treatment - miltefosine - for visceral leishmaniasis. The trial is being
>run by TDR and ASTA Medica, a pharmaceutical company based in Frankfurt,
>Germany. The place is Bihar, most poverty-stricken of Indian states and
>the home of kala-azar. Travelling north from Patna, the capital, to
>Muzaffapur where there are two kala-azar clinics, one is struck by the
>fertility of the land, the lush crops of all descriptions, and wonders w
>hy the pov erty. Hand-in- hand with the poverty goes kala-azar, and
>north of Muzaffapur, where poverty is perhaps even greater, kala-azar
>becomes hyperendemic.
>
>The current drugs for kala-azar all have drawbacks. They are
>administered by injection or infusion and require the patient to be
>hospitalized - miltefosine will be the first oral treatment. Nearly 40%
>of cases in Bihar, where the disease is anthroponotic, are resistant to
>treatment with pentostam. The drug causes serious side-effects -
>mortality in 2-5% of patients and toxicity in 10-15%. The second-line
>treatment, pentamidine, also has serious side-effects, causing 7 -9%
>mortality and 60% toxicity with irre versible damage such as diabetes.
>
>Amphotericin B is most effective, but is also toxic, causing severe
>rigor and fever and sometimes anaphylaxis. It requires infusion every
>other day for 15-20 days, and besides is so expensive as to be
>unaffordable by 95% of patients. In fact, cost is a problem with all the
>treatments available; miltefosine will certainly be cheaper, should it
>reach the market, although the exact price is yet to be determined.
>Affordable cost for target populations is a key feature of all TDR
>product profiles.
>
>In preparation for the trial, a workshop was held in Bihar in early
>July. This was a follow-up to earlier workshops, mentioned in TDRnews
>Nos. 58 and 59, where clinical monitors were trained. Four teams from
>three kala-azar clinics and a laboratory in Bihar, who constitute the
>investigators in the trial, and an international team of three from
>India, Thailand and Viet Nam, who constitute the monitoring team,
>discussed the finer details of the protocol with representatives of ASTA
>Medica. The role of the mon itors is to oversee the trial at the three
>centres to ensure that the rights of the patients are protected and that
>details of all treatments of all patients, including all adverse events,
>etc., are recorded accurately, and that each and every miltefosine
>capsule is accounted for. Between them, a monitor will be on site for
>almost the entire duration of the trial; it is hoped their work will
>hasten the drug's passage through regulatory affairs .
>
>How do the doctors view the new oral treatment? "Compliance is good, and
>earlier trials have shown it to have an overall cure rate greater than
>90%." It is specific, and on the whole not too toxic. "On a
>toxicity:benefit ratio it scores well and on all parameters should be an
>ideal first-line drug" said one investigator. "The major drawback is its
>effect on the foetus, and for this reason it cannot be used as mass
>outpatient treatment - it will need to be monitored all the time.
>However, women constitute on ly 25% of cases (more men are infected
>owing to their habit of sleeping outside), and among female patients,
>only 30% are of child-bearing age. Thus a relatively small number of
>patients will be excluded from treatment on these grounds."
>
>What do TDR and ASTA gain by working together? TDR provides scientific
>and organizational input, and tropical diseases know-how, while ASTA
>provides the full backing and experience of industry. Costs are shared
>50:50 between the two partners, and when finally the drug is ready to
>proceed to the regulatory authorities, the application will be more
>powerful for being backed by both partners. ASTA feels that WHO, through
>its relationship with governments, will help bring the drug to the
>market more quickly, an d views its relationship with WHO as an asset
>and mark of high quality. "Its an example of a relationship that's
>really working" said an ASTA representative.
>
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