In a year when new active substances (NASs) sank to
an all-time low, what are the experts' views of the future
pharmaceutical industry?
Kathy
Ordonez, President of Celera Genomics & Diagnostics,
speaking at Economist Conferences' 10th Annual
Pharmaceutical Conference in London, February 2004, painted
a positive
view of the industry of the near future. She believes: "The
time has arrived for new drugs based on targeted medicine!" In
her view, scale is the key to success in order to replicate
and validate results. Large scale association tools, Ordonez
insists, will facilitate advances in three important areas:
- Diseases
will be subclassified allowing more targeted
medicines
- Identification of new drug
targets
- Finding new diagnostic
markers to stratify patients for increased drug efficacy
and safety
Ordonez's view is that it
will "allow a profound new understanding of human biology
and disease development".
Sir Richard Sykes, former
Chairman of GlaxoSmithKline, identified six technology
areas that will be enablers of new drug discovery and
development in his view:
- Structural biology -
rational design of medicine
- Genetics, genomics, proteomics
- better targeted medicines
- Metabonomics - prediction
of efficacy and toxicity
- Imaging - kinetics and
toxicology prediction
- Nanotechnology - drug
delivery/targeting
- Bioinformatics - new
target identification
Sir Richard thinks that drug
discovery and development should be redesigned to harness
new tools. In his view, there is a need for greater partnering
with the university sector to access new technologies.
Another key driver for the future of the industry, he
believes, is to seek ways of becoming partners within
the future healthcare sector.
Rosy future... but not
quite yet
The trend is still on the decline
for first launches of NASs, according to IMS
LifeCycle New Product Focus' annual
review, which shows only 30 NASs in 2003, versus
36 in 2002.
This marks an all-time low since IMS started monitoring
NASs in the early 1970s, and the lowest in 25 years since
the 32 drugs launched in 1979.
Number of
NASs by year of launch 
Source: IMS LifeCycle New Product Focus
Once again the US topped the charts in terms of
country of first launch, notching up 50% of world
launches - slightly lower than last year's 58%. More
than a quarter of first launches were in Europe (27%),
whilst Japan managed barely 7%; Russia achieved more
first launches than Japan, with 10%. By the end of
2003, only 12 NASs had reached multiple markets.
By far the most successful launches in terms of
number of countries penetrated by year-end 2003 were
the two erectile
dysfunction drugs:
Lilly ICOS' Cialis (tadalafil) reached 40
markets, while Bayer and GlaxoSmithKline's Levitra (vardenafil)
was only a little way behind with 35. The question
remains how quickly they will take market share from
Pfizer's Viagra (sildenafil), the market leader.
Will perceived improvements in dosing and duration
be enough to topple the leader?
Of the other NASs, Abbott's
monoclonal antibody Humira (adalimumab),
a rheumatoid
arthritis treatment,
had launches in three of the four regions (North
America, Europe and Latin America), gaining footholds
in nine countries. The Roche/Trimeris HIV
antiviral Fuzeon (enfuvirtide)
also reached nine markets and achieved launches
in both North America and the EU. AstraZeneca's Crestor (rosuvastatin),
licensed from Shionogi, reached 14 countries in
three regions in 2003. As one might predict, all
first launches in Russia, China and Japan remained
as sole launches by year-end.
Years
from priority patent application to launch
Source: IMS LifeCycle
Development
times show wide variation, but the average is above
the generally accepted norm of 8-12 years,
at 14 years, for the 30 NASs launched in 2003, according
to IMS
LifeCycle Patents Focus.
This is all the more surprising as the received wisdom
would predict below average development times, due
to the high percentage of biotechnology products
launched in 2003 (27%).
A drug that found an
easy path through the development minefield was
the HIV protease inhibitor fosamprenavir, a prodrug
of amprenavir (Agenerase), launched by GSK
as Lexiva in the US in November 2003, following
a fast-track FDA review: co-developed with Vertex,
it took a mere six years to reach the market.
The other fast mover
was Levitra, which took five years to become
the third in class, two months behind second in
class Cialis - which was in development
for nine years. First in class Viagra, launched
in the US in 1998, took just under eight years
to reach the market.
Are long lead-times
a factor in the antibiotic famine?
Only two of the 30 NASs were antibiotics. LG Chem's
third-generation quinolone gemifloxacin (Factive)
was launched in South Korea in June. Factive was
approved in the US, where it is licensed to Genome
Therapeutics, in April 2003 for treating acute exacerbations
of chronic bronchitis and mild-to-moderate community-acquired
pneumonia. As a benchmark, Factive was a fast
mover in comparison with other recently introduced
quinolones: the three launched in 2002 had an average
lead-time of 14-15 years, whereas Factive took
just nine years to make its debut.
Perhaps one of the major factors discouraging companies
from developing new antibiotics effective against
drug resistant strains is the longer lead-times.
This is borne out by the time taken to market for
Cubist's Cubicin (daptomycin), a first in
class lipopeptide antibiotic. Cubicin is effective
against MRSA (methicillin-resistant Staphylococcus
aureus) skin and skin structure infections. Lead-time
for this drug was almost 22 years; original developer
Lilly discontinued work on the product in 1994 before
licensing it to Cubist in 1997.
Biotech drugs take less time
Interestingly, if only the development times of
the eight biotech NASs are considered, the average
development time reduces to 12 years. Only one of
the biotech products showed a really rapid development
time, of just five years: the recombinant alpha-L-iduronidase
enzyme laronidase (Aldurazyme), for mucopolysaccharidosis
I. Jointly developed by BioMarin and Genzyme, it
has Orphan Drug status in the US, EU and Japan, and
was launched in the US, Germany and Finland.
Lead-time for biotech drugs in general is lower
than average, but not as impressive as first hoped.
A possible mitigating circumstance is that many of
these treatments represent first in class drugs that
often take longer than subsequent market entrants.
Development stage at first licensing
Source: IMS LifeCycle R&D
Focus
There is also a wide variation in licensing patterns
for the NASs. Some were developed and marketed by
the originator company and since they had multinational
reach, they did not rely on licensing-out activity.
At the other extreme, some drugs were the subject
of early-stage licensing or co-development deals
and then late-stage licensing or co-promotional deals.
Development stage at licensing
Source: IMS LifeCycle R&D Focus/Patents
Focus
According
to Celltech Group CEO Goran Ando, speaking at the Economist
Conferences event, the biotech sector is maturing and licensing
deals between
pharma companies and the biotechs are changing, providing
more variations and better deals for the biotech sector.
|
Then |
Now |
|
Signature fee/milestone
payments |
Profit splitting |
|
Single digit royalties;
no commercialisation rights |
Co-marketing/co-promotion
deals |
|
No development contribution |
Geographic and indication
deals |
|
Little actual collaboration |
Joint ventures |
Perhaps as the biotech companies
mature, they will encourage further adoption of newer
approaches to drug development by the entire industry,
resulting in higher numbers of new drug launches in future
years.
This article was written by
Irene Buggle, Manager of the Drug Information group at
IMS, which includes the LifeCycle portfolio of
products. For further information on LifeCycle or
any of its constituent publications, please contact Stephanie
Earle via e-mail or call +44 207 393 5515.
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