R&D
Improved clinical outcome, in terms of
renal cell carcinoma
Antigenics filed for EU approval of its
significantly improved PFS, was achieved with
The good news for the relatively rare, but
therapeutic kidney cancer vaccine, Oncophage
the combination in patients progressing on
hard-to-treat, kidney cancer continued in 2008,
(HSPPC-96; vitespen), as an adjuvant treatment
Herceptin-based therapy. The role of combined
with further success for the targeted therapies
in the disease, under the conditional
anti-HER2 therapy, in combination with which have recently changed the face of this
authorisation provision, following Russian
chemotherapy, in less heavily pre-treated disease. Novartis filed its mTOR inhibitor
approval in 2008. The vaccine failed to meet its
patients with early stage disease is ongoing in Afinitor (RAD-001; everolimus) in the US and
primary relapse-free survival endpoint in its
pivotal trial, which included various stages of
the ALTTO (Adjuvant Lapatinib and/or EU for the treatment of patients with
kidney cancer, but appeared to show a benefit in
Trastuzumab Treatment Optimization) study.
advanced kidney cancer who have failed on
standard treatment. The filings were based on
Stage I and II patients (intermediate-risk), the
prostate cancer
population in which Antigenics hopes to secure
data from the RECORD-1 trial, in which most
approval.
Despite prostate cancer having one of the patients received RAD001 as a third-line
Meanwhile, despite the significant progress
best prognoses of any tumour type, like breast therapy. PFS was the primary endpoint of the
made in kidney cancer in the clinic, the UK’s
cancer it remains one of the biggest killers study, which was terminated early when a large
National Institute for health and Clinical
due to high incidence and not being caught
benefit with RAD001 compared with placebo
Excellence (NICE) released draft guidance, amid
early in all cases. Much of the focus of drug
was observed – median PFS was 4.0 months
significant controversy, which said that Avastin,
discovery is on hormone-refractory prostate
vs 1.9 months.
Nexavar, Sutent and temsirolimus (Wyeth’s
cancer (HRPC), as there are few options for
The trial’s lead investigator said that
Torisel) were too expensive to be made
the men who develop this late-stage
RAD001 should be the standard of care for
available on the NHS in England and Wales. This
condition.
patients who progress on a VEGF receptor
highlighted the cost-effectiveness hurdles that
There was more disappointment for GPC
tyrosine kinase inhibitor (ie, Pfizer’s Sutent
even the most promising anticancers will have to
Biotech, which announced this year that the
(sunitinib) or Bayer/Onyx’s Nexavar), since no
face, especially in some healthcare systems.
EU marketing application for its oral platinum-
other drug has shown a benefit in this setting
in a large trial. However, other experts said
based chemotherapy drug satraplatin was to
chronic lymphocytic leukaemia
that more work needed to be done to
be withdrawn by its partner for the drug in
Chronic lymphocytic leukaemia (CLL), an orphan
establish the best sequence of therapies in drug indication and the most common form of
Europe, Celgene (previously Pharmion). There
kidney cancer, with the numerous new options adult leukaemia, saw significant activity this year.
had been high hopes for satraplatin as a
on the market and other second-generation First, in March, the FDA approved Cephalon’s
second-line agent in HRPC (after failure of
drugs that target VEGF receptors, which new chemotherapy drug Treanda (bendamustine
other chemotherapy) after it prolonged PFS,
include GlaxoSmithKline’s pazopanib and HCl) for CLL, its first indication, after it showed
but last year GPC announced the
Pfizer’s axitinib, in late-stage trials. in a pivotal study in treatment-naive patients to
disappointing news that satraplatin had failed
Meanwhile, overall data from Sutent’s pivotal have a higher rate of overall response and longer
to extend overall survival in the pivotal
trial became available in 2008. Overall survival
PFS compared with standard chlorambucil
SPARC trial. Pharmion had said that the key
in the trial was 26.4 months for Sutent vs
chemotherapy. Treanda also secured approval for
for the European submission would be to
21.8 months for alpha-interferon. However, the
the treatment of relapsed indolent non-
conduct pre-specified subset analyses focusing
most informative data, according to experts,
Hodgkin’s lymphoma (NHL).
on the impact of prior use of Sanofi-Aventis’s was that showing the comparison of Sutent
Genentech/Roche/Biogen Idec’s Rituxan/
chemotherapy Taxotere (docetaxel), but this and alpha-interferon for patients who did not
MabThera (rituximab), a blockbuster drug in its
failed to sway the European agency. get any post-study treatment. For these
primary indication of NHL, succeeded in two
Other disappointments included Cell patients, median survival was doubled with
pivotal trials in CLL in combination with
Genesys’s GVAX and Dendreon’s cellular
Sutent – 28 months vs 14 months. 14 months
chemotherapy in previously untreated patients
therapy Provenge (see above), but hopes still
has been the traditional survival duration seen
and in relapsed patients. Roche filed for EU
remain for Provenge to improve overall
with interferon before the advent of the new
approval for rituximab as a first-line agent in CLL
survival in the final analysis expected mid-
targeted therapies in kidney cancer, showing
after it met its PFS endpoint in the CLL-8 trial in
2009. If approved in the US, it would be the
that the lengthened survival for patients
previously untreated patients.
first immunotherapy for cancer and would
treated with interferon in the overall trial
Finally, GlaxoSmithKline and Genmab said the
give a significant boost to the field.
population was likely due to the post-study
pivotal, single-arm, single-agent Phase III trial of
One prostate cancer success was Ferring
treatments.
ofatumumab met its primary response endpoint
A disappointment in renal cancer was
at interim analysis in refractory CLL. If approved,
Pharmaceuticals’ degarelix, which is to be used
Oxford BioMedica’s TroVax, a novel
CLL would be the first indication for
in men who are still responsive to hormonal ofatumumab which, like rituximab, targets the
therapeutic cancer vaccine being developed
treatment rather than in HRPC. Ferring filed CD20 antigen on the surface of normal and
with Sanofi-Aventis. Oxford BioMedica said it
the drug, a GnRH antagonist, in the US and malignant B-cells. However, it is a fully human
would not meet its predefined primary
EU after successful completion of a pivotal
monoclonal antibody, while rituximab is
endpoint of a survival benefit in its pivotal
Phase III trial that compared it with Abbott’s
chimaeric. It also targets a novel epitope of
Phase III TRIST study after a fourth interim
Lupron (leuprolide acetate), a standard GnRH
CD20, and preclinical studies indicated that it is
analysis was conducted. However, the UK
agonist. The GnRH antagonists, in contrast
associated with greater complement-dependent
biotech company subsequently said the FDA
with the agonists, do not cause an initial
cytotoxicity than rituximab.
supported its proposed amendments to the
increase in testosterone and therefore have a
study design, which will look at whether
faster onset of action in reducing levels of the
patient outcome is dependent on the number
Malini Guha is Scrip’s
hormone. Whether this leads to better clinical
science editor.
of doses, background standard of care and
outcomes is not yet known. However, patients patients’ prognostic factors. However, an
on these drugs would not need to also take additional confirmatory clinical study in this
an anti-androgen therapy. indication will still be needed for approval.
www.scripnews.com/supplements Scrip 100
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