Novantrone Study Data Reports Significant Delay in Disability Progression
And Decrease in Incidence of Attacks
STOCKHOLM, Sweden, Sept. 10 /PRNewswire/ -- Researchers at the 14th Congress
of the European Committee for Treatment and Research in Multiple Sclerosis
(ECTRIMS) reported today that in preliminary results of a Phase III clinical
trial, Novantrone(R) (mitoxantrone for injection concentrate) had a
statistically significant impact on relapse rate and disability progression in
patients with progressive multiple sclerosis (MS). Magnetic resonance imaging
(MRI) data were also reported that corroborated the clinical findings.
Novantrone was administered by short, IV infusion once every three months in
this trial. Other treatments currently approved for MS require a subcutaneous
or intramuscular self-injection on a daily or weekly basis.
"While current therapies have provided a major step forward for the treatment
of multiple sclerosis, there is still a need for new therapy options for
people with the disease," said Jeanne Oates Angulo, President of the National
Capital Chapter of the National Multiple Sclerosis Society. "We look forward
to learning more about Novantrone and the scientific communities evaluation of
these clinical results."
Multiple sclerosis is a highly debilitating illness that afflicts more than
300,000 Americans and more than one million people worldwide. This autoimmune
disease attacks the central nervous system. The nerve fibers of the brain and
spinal cord are insulated by a fatty substance called myelin, which helps
conduct the flow of nerve impulses to and from the brain. But in people with
MS, myelin is damaged, causing scar tissue, or sclerosis, that can distort or
even block messages from the brain. This can result in a variety of symptoms
that range from numbness in the limbs to complete paralysis.
Novantrone is currently marketed to treat pain in patients with advanced
hormone-refractory prostate cancer in combination with corticosteroids and for
initial therapy of acute nonlymphocytic leukemia. It is not approved for use
in MS patients.
"We are encouraged by the results with Novantrone reported in this study,"
said Peggy Phillips, senior vice president, pharmaceutical development,
Immunex Corporation (Nasdaq: IMNX). "We are looking forward to meeting with
the Food and Drug Administration to discuss applying for an expanded label for
the use of Novantrone in MS."
The Phase III, multicenter, placebo-controlled, randomized, observer-blind
trial in 194 patients with progressive MS assessed the effects of Novantrone
on disease progression. The study investigators compared two doses of
Novantrone -- 12 mg/m2 and 5 mg/m2 -- with placebo, and administered each
treatment intravenously once every three months for two years.
There was a statistically significant difference in the duration of time from
initiation of treatment to the first severe MS attack, defined as the
occurrence of a new symptom or the worsening of an existing symptom that
requires treatment with corticosteroids, the most commonly used medication for
controlling such episodes. The median time to first relapse was not reached
after 24 months for both of the Novantrone doses and was 15 months for the
placebo group.
The difference in annual relapse rates was also significant, with a rate of
21% in the Novantrone 12 mg/m2 dose group compared to 60% for placebo. The
relapse rate was 36% for the 5 mg/m2 dose. The percentage of patients who had
confirmed treatment failure was 7% for the 12 mg/m2 dosage, 9% for the 5 mg/m2
dosage, and 19% for placebo.
The study investigators also used MRI in a subgroup of 110 patients at 12 and
24 months. The MRIs detected almost no additional lesions (scar tissue), an
objective indicator of disease progression, in either the 5 or 12 mg/m2
Novantrone groups. In the placebo group, however, the MRI found a continuous
increase in lesions at 12 and 24 months. There was a significant decrease in
gadolinium-enhanced lesions in the 12mg/m2 group as compared to the placebo
group.
Investigators also reported that patients receiving Novantrone had an
improvement of their neurologic function as measured by the Expanded
Disability Status Scale (EDSS), the standard clinical rating scale used to
evaluate disability progression in MS clinical trials. The EDSS measures
disability based on the level of neurologic impairment. The EDSS rates a
patient's level of function from zero (normal neurological exam) to 10 (death
due to MS), with every half-point increase on the scale representing a
progressive deterioration of ability. Mean change from baseline in EDSS score
was -0.13 for patients receiving the 12 mg/m2 dose and -0.23 for the 5 mg/m2
dose compared to +0.23 for placebo.
In addition, patients who received Novantrone had less deterioration of their
mobility based on scores from the Ambulatory Index (AI), another measure of
patient symptoms and disease progression. The AI rates a patient's mobility
from zero (asymptomatic or fully active) to nine (restricted to wheelchair and
unable to transfer independently). The mean change in score for Novantrone
doses was +0.30 for the 12 mg/m2 dose and +0.41 for the 5 mg/m2 dose compared
to +0.77 for placebo.
Overall, treatment with Novantrone resulted in generally manageable side
effects in this trial. The most frequently reported side effects were
neutropenia (a reduced number of white blood cells), infection and alopecia
(hair loss), which occurred in 11, 10 and 5 percent of the patients
respectively.
Novantrone has been studied in MS preclinically and clinically for over a
decade. The results of this Phase III study are consistent with the outcomes
from these earlier trials. In several experiments of a model of MS,
Novantrone showed prevention of disease relapse and progression in mice. These
preclinical studies led to the start of investigations in several countries of
Novantrone in patients with MS. Several Phase I and II trials were conducted
that showed a reduction in new lesions on MRI, as well as reductions in the
number and severity of relapses in Novantrone-treated patients.
Immunex holds the marketing rights for Novantrone in North America. Wyeth-
Ayerst International, which is a division of American Home Products, markets
Novantrone outside North America.
Immunex Corporation is a biopharmaceutical company dedicated to developing
immune system science to protect human health. The company's products offer
hope to patients with cancer, inflammatory and infectious diseases.
American Home Products Corporation owns a majority interest in Immunex. AHPC
is one of the world's largest research-based pharmaceutical and health care
products companies and is a leading developer, manufacturer and marketer of
prescription drugs and over-the-counter medications. It is also a leader in
vaccines, biotechnology, agricultural products and animal health care.
For full prescribing information for Novantrone, please call Lisa Crisera,
206-389-4346. For assistance determining insurance coverage, please call the
Immunex Reimbursement Hotline 800-321-4669.
NOTE: This news release contains forward-looking statements that involve
risks and uncertainties, including risks associated with clinical development,
regulatory approvals, product commercialization and other risks described from
time to time in the SEC reports filed by Immunex, including the most recently
filed Form 10-Q.
An electronic version of this news release -- as well as additional
information about Immunex of interest to investors, customers, future
employees and patients -- is available on the Immunex web site at
www.immunex.com.
SOURCE Immunex Corporation
CO: Immunex Corporation
ST: Washington, Florida, Sweden