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Targeted Genetics Corporation
TARGETED GENETICS ANNOUNCES PRELIMINARY RESULTS OF PHASE I
CLINICAL TRIAL OF tgAAC94 IN PATIENTS WITH INFLAMMATORY ARTHRITIS
Results demonstrate safety and support continued study of tgAAC94 in
conjunction with TNF- antagonists in inflammatory arthritis
Seattle, WA July 26, 2005 Targeted Genetics Corporation (NASDAQ: TGEN) today announced that the
preliminary results from its Phase I clinical trial of tgAAC94 in patients with inflammatory
arthritis demonstrate that the experimental drug is well tolerated and can be safely administered
directly into joints of patients with inflammatory arthritis. Preliminary data suggest
improvements in signs and symptoms of arthritis in the treated joints.
The trial conducted in the United States and Canada was a multi-center trial of tgAAC94 injected
locally into the arthritic joint. Fifteen patients who enrolled in the trial were randomized to
receive either one of two escalating dose levels of tgAAC94 (n=11) or a placebo (n=4). The trial
contained a placebo arm at each dose level, which was included primarily to assess whether any
adverse events that might be seen were attributable to an intra-articular injection itself, as
opposed to an intra-articular injection of tgAAC94.
The primary objective of the study was to evaluate safety of intra-articular injection of tgAAC94
in patients not on concomitant systemic tumor necrosis factor alpha (TNF- antagonist
therapy. The data demonstrate that tgAAC94 was well-tolerated at doses up to 1x1011 DRP
per mL of joint volume. Data was also collected on secondary parameters including improvements in
arthritis signs and symptoms in the injected joint as measured by changes in joint swelling and
tenderness using standardized arthritis index scores. Although the number of patients was small,
in those treated with tgAAC94 and followed for four weeks, there was an indication of sustained
improvement in signs and symptoms in nine of the eleven subjects. From continued follow up, the
preliminary data also indicate that seven out of nine patients who received tgAAC94, and who have
been evaluated through week eight following treatment, experienced
sustained improvement in signs and symptoms of disease. In those subjects receiving placebo,
improvements in arthritis signs were noted in two out of four subjects.
The trial has now been closed for enrollment and patients will continue to be followed for 24 weeks
after injection. Additional clinical results will be reported at the next appropriate scientific
The preliminary results of this trial represent a key milestone in the development of our
inflammatory arthritis program, said H. Stewart Parker, president and chief executive officer of
Targeted Genetics. Based on the results of this trial, we expect to advance the development of
tgAAC94 into the next stage of clinical development; including localized treatment of patients who
are concurrently receiving systemic anti-TNF therapies, but who continue to suffer from one or more
affected joints. We expect to begin the next clinical trial of tgAAC94 in the third quarter of
Over the past decade, advances in inflammatory arthritis drug discovery and development have
identified TNF- as a key mediator of disease-related inflammation and tissue damage. While
anti-TNF- therapies are now widely used in the treatment of inflammatory arthritis, there
are a number of patients taking systemic anti-TNF- therapies who do not fully respond to
those therapies and still have one or several affected joints. tgAAC94 is an AAV-based product
containing the gene for the soluble TNF- receptor protein. tgAAC94 is delivered directly to
the affected joint where it should express the soluble TNF- receptor protein locally and on
In spite of advances in treatment options, particularly the use of systemic anti-TNF- therapies,
a significant number of patients with inflammatory arthritis do not experience an adequate response
and have ongoing destructive inflammation in select joints. These patients are potentially ideal
candidates for a localized, more concentrated delivery of anti-TNF- therapy to the joint,
said Philip Mease, M.D., Chief, Rheumatology Clinical Research Division of Swedish Hospital Medical
Center, Head of Seattle Rheumatology Associates, and a lead investigator in this clinical trial.
Though the patient numbers are relatively small and the study is not powered to show efficacy, I
am encouraged that delivery of tgAAC94 directly into affected joints appears to be safe and has the
potential to reduce signs and symptoms of arthritis. I am excited to begin additional studies
using Targeted Genetics interesting approach to address this ongoing treatment challenge.
In June 2004, the Company reported that in preclinical studies, rAAV-rat TNFR:Fc was delivered to
the joints of rats with experimentally induced arthritis. The data from these studies
demonstrated that a single injection of rAAV-rat TNFR:Fc vector into the ankles of arthritic rats
resulted in a significant reduction in ankle and hind paw swelling as measured by arthritis index
scores. The data also indicated that animals treated in a single joint experienced a reduction in
swelling in the untreated joint as well as the treated joint. This was observed in the absence of
significant levels of circulating TNFR:Fc protein. Preclinical evaluation of safety showed that
rAAV-TNFR:Fc was safe and well tolerated.
About tgAAC94 and AAV technology
tgAAC94 uses Targeted Genetics Corporation s rAAV (recombinant AAV) vector technology and contains
a gene that encodes the soluble TNF- receptor. The soluble TNF- receptor is a
TNF- inhibitor. tgAAC94 is delivered directly to affected joints to induce the patient s
own joint cells to produce local concentrations of the TNF- inhibitor to reduce inflammation
associated with disease. tgAAC94 is being developed as a potential supplement to systemic
anti-TNF- protein therapy for use in patients with inflammatory arthritis where one or
several joints do not
respond to systemic protein therapy. Local administration of a DNA sequence encoding a soluble
TNF- receptor potentially may supplement currently used drugs in a number of inflammatory
conditions. In addition, a locally administered anti-TNF- therapy could also be useful in patients
having a limited number of joints impacted by inflammatory arthritis who are at a risk for
progressive joint damage but who may not require systemic therapy. The characteristics of AAV
vectors make them well suited for delivery of genetic material to joints and other local
environments. The Company s rAAV technology platform is used to deliver genes and is
based on AAV, a naturally occurring virus that has not been associated with any disease in humans.
About Targeted Genetics
Targeted Genetics Corporation develops molecular medicines for the prevention and treatment of
acquired and inherited diseases. The Company has clinical product development programs targeting
inflammatory arthritis and AIDS prophylaxis. The Company also has a promising pipeline of
preclinical product development programs focused on congestive heart failure, Huntington s disease,
and hyperlipidemia. For more information about Targeted Genetics, visit its website at
Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995:
This release contains forward-looking statements regarding our intellectual property, research
programs and clinical trials, our product development and our potential development platforms
including tgAAC94 and other statements about our plans, objectives, intentions and expectations. In
particular, the statements regarding the Company s pipeline, ability to maintain patients in the
trial for follow-up and future clinical trial plans are forward-looking statements. These
statements, involve current expectations, forecasts of future events and other statements that are
not historical facts. Inaccurate assumptions and known and unknown risks and uncertainties can
affect the accuracy of forward-looking statements. Factors that could affect our actual results
include, but are not limited to, initial trial results not indicative of results from the
completion of the trial, the timing, nature and results of our clinical trials, potential
development of alternative technologies or more effective products by competitors, our ability to
obtain and maintain regulatory or institutional approvals, our ability to obtain, maintain and
protect our intellectual property and our ability to raise capital when needed, as well as other