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The field of gene therapy had hardly reached its infancy
when it was severely shaken by the death of a trial participant,
precipitating a string of disaster stories in the general
media. However, recent events could be viewed as somewhat
of a rejuvenation for this still immature field.
A litany of disaster
Since the death of Jesse Gelsinger in a trial held at the
University of Pennsylvania in September 1999, the field
of gene therapy has been subjected to close scrutiny by
both the US Food and Drug Administration and the media.
Concomitantly, the field has had to overcome a series of
hurdles since Jesse Gelsinger's demise:
- A number of inconsistencies were found within the
trial, including lack of informed consent and ineligibility
of Jesse Gelsinger to enrol
- Inconsistencies found in other gene therapy trials,
including conflicts of interest and lack of reporting
of adverse events
- Shutdown of all six University of Pennsylvania gene
therapy trials
- Canji requested by US FDA to suspend further trials
with a gene therapy product
- University of Pennsylvania announces end to further
gene therapy trials
However, since June 2000, the field, described by Professor
Savio L. C. Woo, President of the American Society of Gene
Therapy (ASGT), as being "in its infancy as a biomedical
discipline", achieved some positive goals.
Positive annual meeting builds confidence
The ASGT held its annual meeting at the beginning of
June. Positive data were reported from Phase I and II trials
involving patients with severe combined immunodeficiencies
(SCID) and haemophilia B. Over the next few days, positive
results were also reported from other clinical trials involving
patients with melanoma and cystic fibrosis, as well as other
cancers.
Importantly, in the light of the University of Pennsylvania
trial, sessions were addressed to the safety issues associated
with the different vectors used in gene therapy. In the
context of new data from ongoing clinical trials, however,
only three records were updated on the R&D
focus database, out of a total of 32 updated from the
meeting.
New Phase III trials a welcome boost
Since the beginning of June, another important boost for
the field has been the initiation of three Phase III cancer
trials in the USA with three different adenoviral-based
gene therapy products. At the ASGT meeting, Canji (the gene
therapy division of Schering-Plough) announced that it had
commenced a Phase III trial with SCH 58500.
Subsequently, in the few days following the meeting, it
was announced that Phase III trials had commenced with ONYX
015, developed by Onyx Pharmaceuticals and Warner-Lambert
(now Pfizer), and with INGN
201, which has emerged from Introgen's collaboration
with Aventis.
That all these trials are for cancer treatments reflects
the fact that the majority of gene therapy clinical trials
are in oncology.
Table: Gene Therapy products recently entering Phase
III
|
Product
|
Company
|
Indication
|
| INGN
201 |
Introgen,
Aventis |
Head
and Neck Cancer |
| ONYX
015 |
Onyx,
Warner-Lambert (Pfizer) |
Head
and Neck Cancer |
| SCH
58500 |
Canji
(Schering-Plough) |
Stage
III Ovarian Cancer |
Source:
R&Dfocus, part of the LifeCycle
database
In some respects, Canji's SCH 58500 may be seen as a test
case. Enrollment into clinical trials involving SCH 58500
was temporarily suspended in October 1999, on request from
the US FDA, following the death of Jesse Gelsinger. However,
an ongoing Phase II trial was subsequently reopened.
Whether the initiation of these three Phase III trials heralds
a revival in the fortunes of this new field is not clear.
New data reported in the August issue of Nature Medicine,
from a Phase II trial involving ONYX 015, point to a positive
effect.
Objective clinical responses were seen in patients with
head and neck cancer when the gene therapy was used in combination
with conventional chemotherapy. However, upon the announcement
of the new trial for SCH 58500, it was also indicated that
results would be five years in the coming.
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