New Drugs

First some history.

In the early part of the twentieth century it was considered an impossibility that any drug might be discovered that could effectively kill the TB bacillus. Then, suddenly, a research frenzy developed as animal experiments began to look more promising. But after the frantic research activity in the 40s, 50s and early 60s, there was literally no new drug research for TB until the last few years - despite TB remaining for most of this period the most lethal infectious disease for humankind.

In 1944 streptomycin was discovered, the very first drug identified as killing the TB bacillus.

By 1948 the first signs of resistance to it were fully recognised. In the same year the first combination therapy was introduced (Streptomycin and PAS - both now relegated to being second line drugs).

The current four first line drugs were all patented between 1952 and 1966. Not only does this mean that all of the approved TB drugs are comfortably out of patent, but it also unfortunately means that TB, despite its ubiquitousness, could be reasonably classified as a "neglected" disease, something which has now become a humanitarian tragedy.

New drugs

There are currently some promising candidates in the pipline, but the questions are-

How expensive will each be? (Or rather will they be affordable to those most in need of them?)

How will each one be used?

The cost

It's impossible to be remotely accurate in any assessment except to say that any developer will be looking to recoup the cost of research. A recent estimate suggests that it costs today as much as $1.2 billion to get a new drug through to full approval (and takes 6-11 years). It's unlikley that either will be the case for a new TB drug because genuine efforts are being made to short cut and short change the process. Nonetheless, it's still questionable whether there is sufficient funding motivation (or time) to support this whole process for a new drug for TB unless drug resistance spreads significantly into the developed world to help promote investment..there are certainly signs that the existing drug development is struggling for funding since new developments are being slightly overhyped.

We would suggest that a single new drug (even if it is "short course" of a couple of months which is the holy grail) is unlikely to cost less than $500 per patient. Would this be affordable in Africa?... Unlikely in many countries as things stand.

If we're contemplating a new combination therapy of new drugs, however (something which could be vital to prevent more extensive drug resistance) we could possibly quadruple that figure of $500.

How will it be used?

This is a much more sensitive question. Two issues will need to be confronted before any new regime is widely implemented - the known risk of fresh resistance, the consequential risks of the drug is inadequately prescribed, and the drug's potential applicability in the real-world of lack of diagnostic infrastructure.

Frankly, whilst there are some known promising candidates, it's difficult to be optimistic about their immediate widespread use.

Practically speaking, a new drug could be implemented three ways:

- on its own, in which case early resistance could be predictable

- automatically alongside existing drugs without drug resistant diagnostics - a practical solution if it is affordable, but do the risks of further drug resistance still exist in this scenario of treating cases of unclassified PDR-TB?

- alongside the full armoury of existing drugs and diagnostics - a realistic option for the developed world but an unaffordable non-starter for those at most risk from this disease.

The clear possibility exists that a single new drug might have to be withheld from populations most in need of it simply because of the existing lack of diagnostic and administrative infrastructure needed to support its application. The perceived global risk of promoting resistance to a new drug from any misapplication could well over-ride any self-evident and recognised desperate need.

The bottom line, as we see it, can be summarised in the frank words of Dr Jim Yong KIm, former Director of the WHO HIV/AIDS Department and now President of the World Bank:

 "It's not just one or two drugs. We need four or five immediately."