[Ip-health] Financial Times: Corners are cut in order to bring drugs to Africa

[Thiru Balasubramaniam]

<SNIP>

"We urgently need to increase usage," says Bernard P=E9coul, head of
DNDi, who expresses his frustration that despite successfully treating
patients with similar combination drugs for malaria since the early
1990s, uptake in affected parts of the world still remains limited
today.

But to its critics, Asaq is a step backwards, because its developers
opted to bypass the stringent standards of developed-world regulators
and instead gained quick approval in Morocco, based on relatively
limited scientific data.

At the core of the debate is the tension between a desire to save as
many lives as quickly as possible and a concern to ensure that patients
in the developing world do not receive medicines of poorer quality and
efficacy than would be approved in richer countries.

"We realise that Sanofi's aim is to get the drug launched quickly.
However, applying a different standard for drugs aimed at Africa
invites unnecessary questions," says Chris Hentschel, head of the
Medicines for Malaria Venture, another non-profit group, which is
developing a range of treatments for the parasite. His and similar
research groups have been created since the late 1990s to fill a gap:
developing innovative treatments for "neglected diseases" in the
developing world for which the markets are too modest to interest
industry. The aim was to meet western standards, ending an era of
second-rate "poor drugs for poor people".

<SNIP>

A final difficulty for regulators is safety surveillance after the
launch of new medicines in the developing world, where there are
limited systems to pick up side-effects that could trigger withdrawals
or require prescription practices to be modified. "When you are putting
the drug into the bush, you have a much more serious responsibility
than you do in Europe," says Lembit Rego, who scrutinises drug
applications for the World Health Organisation.


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Corners are cut in order to bring drugs to Africa

By Andrew Jack

Published: March 30 2007 03:00 | Last updated: March 30 2007 03:00

When a French pharmaceutical company teamed up with a Swiss charity
this month to launch a low-cost malaria drug for Africa, the news
caused as much concern as rejoicing among international health experts.

Asaq - named after its two constituents, the drugs artesunate and
amodiaquine, combined into a single pill - offers a relatively
affordable and simple treatment for a parasite that kills more than 1m
people a year and causes substantial economic upheaval.

To its champions, it marks a first success for one of a growing number
of "product development partnerships", twinning the Drugs for Neglected
Diseases initiative (DNDi) in Geneva, a non-profit organisation that
co-ordinates academic research groups, with Sanofi-Aventis, the French
pharmaceuticals producer.

"We urgently need to increase usage," says Bernard P=E9coul, head of
DNDi, who expresses his frustration that despite successfully treating
patients with similar combination drugs for malaria since the early
1990s, uptake in affected parts of the world still remains limited
today.

But to its critics, Asaq is a step backwards, because its developers
opted to bypass the stringent standards of developed-world regulators
and instead gained quick approval in Morocco, based on relatively
limited scientific data.

At the core of the debate is the tension between a desire to save as
many lives as quickly as possible and a concern to ensure that patients
in the developing world do not receive medicines of poorer quality and
efficacy than would be approved in richer countries.

"We realise that Sanofi's aim is to get the drug launched quickly.
However, applying a different standard for drugs aimed at Africa
invites unnecessary questions," says Chris Hentschel, head of the
Medicines for Malaria Venture, another non-profit group, which is
developing a range of treatments for the parasite. His and similar
research groups have been created since the late 1990s to fill a gap:
developing innovative treatments for "neglected diseases" in the
developing world for which the markets are too modest to interest
industry. The aim was to meet western standards, ending an era of
second-rate "poor drugs for poor people".

But as private philanthropic support for such drug development
partnerships has gathered pace, matched by a consciousness of corporate
responsibility on the part of the drug companies, regulators have
proved slow to respond to the resulting pipeline of experimental
medicines and vaccines nearing launch.

One problem for such developers is that the regulators' assessment of
the relative balance of risks and benefits of a new medicine or vaccine
in the developed world is not the same as for their counterparts in
poorer countries, because of the greater burden of disease and the
lower level of medical resources available.

For example, when Wyeth's pioneering RotaShield vaccine for rotavirus -
a gastric infection that causes thousands of hospitalisations each year
but very few deaths in the US - was linked to an extremely rare but
serious side-effect in 1999, the company withdrew it from the market.

But in the developing world, where rotavirus causes up to 500,000
deaths a year and access to hospital care is less easy, the
side-effects have since been judged to outweigh the risks. That is one
reason why GlaxoSmithKline sought regulatory approval first for its
rival Rotarix vaccine in Mexico, in 2004.

Mr P=E9coul from DNDi cites a similar reason for why, after initial talks
with the MHRA, the British drugs regulator, about authorising Asaq, he
decided to go elsewhere. It told him that he would need to conduct a
full and lengthy clinical trials because the treatment contained
artesunate, which is not yet approved for use in Europe, where malaria
is rare.

Since 2004, the European Medicines Agency (Emea) has launched a partial
solution with a special regulatory pathway for drugs for the developing
world, dubbed Article 58. The US Food and Drug Administration is
considering a similar approach.

The Emea has already approved three drugs using this approach. GSK this
week applied to it for approval of Globorix, a combination vaccine to
protect against multiple childhood diseases including meningitis.

A second task for regulators is how to evaluate drugs that are
reformulations of existing medicines. Mr P=E9coul argues that Asaq falls
into this category. It combines in a single pill two malaria treatments
that have been shown to work in the developing world. Asaq was
developed because patients often abuse the existing treatment - and
risk triggering drug resistance - by taking the artesunate while
throwing away the amodiaquine, which has unpleasant side-effects.

However, Brian Greenwood, a malaria expert at the London School of
Hygiene and Tropical Medicine, says: "When you combine two pills, one
drug can affect the other and you can get reduced activity, different
absorption rates, stability and reactions."

A final difficulty for regulators is safety surveillance after the
launch of new medicines in the developing world, where there are
limited systems to pick up side-effects that could trigger withdrawals
or require prescription practices to be modified. "When you are putting
the drug into the bush, you have a much more serious responsibility
than you do in Europe," says Lembit Rego, who scrutinises drug
applications for the World Health Organisation.

Attention will now turn to his agency, which needs to study Asaq before
many donor agencies and developing-country regulators will purchase it
or approve its use.

Meanwhile, Mr Hentschel says he has faced questions from donors
inspired by Asaq's fast-track tactics but insists on taking a more
cautious approach.

"Millions of people depend on anti-malarials to save their lives and we
would feel more secure if a stringent regulatory authority reviewed the
history and clinical data and gave its stamp of approval," he says.

Andrew Jack

---------------------------------
Thiru Balasubramaniam
Geneva Representative
Knowledge Ecology International (KEI)
voice +41.22.791.6727
fax +41.22.723.2988
mobile +41 76 508 0997
thiru@keionline.org