Here is the full press release from oral Panretin. I don't find this particularly concerning since the safety profile is excellent and oral Panretin has some terriffic activity against significant patient populations. Sure, it is a bit dissappointing that Panretin doesn't cure EVERYTHING that ALRT tested it on but the results they have so far indicate that Panretin has activity in a number of indications (and the cancer progression inhibitory activity may make it usefull in the future as a combination drug but they are wise not to blow scarce resources on this now). If ALRT came to the market with a drug that was well tolerated and significantly benefited psoriasis and Kaposi's sarcoma patients what investor wouldn't be happy? I still have some hope that some of the other cancer populations may respond to Panretin.
Ed
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ALRT Announces Oral Panretin Clinical Trials Update - AIDS Malignancy Consortium Advances KS
Trial -
PR Newswire, Tuesday, July 08, 1997 at 16:18
SAN DIEGO, July 8 /PRNewswire/ -- Allergan Ligand Retinoid Therapeutics,
Inc. (ALRT) (NASDAQ:ALRI) announced today an update on the status of clinical
trials with one of its lead products, Panretin(TM) (9-cis-retinoic acid) Oral
capsules. In the areas of Kaposi's sarcoma (KS), psoriasis and
myelodysplastic syndrome (MDS), trials are continuing in view of evidence of
significant activity. In renal cell cancer, non-Hodgkin's lymphoma and
multiple myeloma, patient accrual to trials will be discontinued due to
insufficient activity, and in proliferative vitreoretinopathy (PVR) due to
inability to accrue patients in this small patient population.
Patient accrual continues to clinical studies sponsored by the company of
ovarian cancer, acute promyelocytic leukemia (APL) and prostate cancer.
Breast cancer, pediatric malignancies and the reversal of bronchial metaplasia
(a premalignant lung condition) studies are being conducted under the
sponsorship of the National Cancer Institute and are also continuing patient
accrual.
"We are pleased with the progress the Ligand and Allergan clinical groups
are making in developing Oral and Topical Panretin and believe focusing on the
trials with the most promising activity is a prudent use of resources," said
Marvin Rosenthale, Ph.D., President of ALRT. "Cancer represents a diverse
group of targets for the retinoids and we expected to see differences in
activity across a variety of tumor types and indications. The emerging
results of our Phase II program are confirming activity in KS and MDS and
finding insufficient activity in renal cell carcinoma, non-Hodgkin's lymphoma
and multiple myeloma. Our results in patients with psoriasis suggest that
Oral Panretin has significant activity and therefore, may have application in
benign dermatological conditions. We continue to assess the activity of Oral
Panretin in our Phase II program for appropriate target indications to pursue
in pivotal Phase III studies for product registration, potentially worldwide.
We expect to announce the selection of these additional indications later this
year.
"Our international, pivotal trial with Oral Panretin in newly diagnosed
APL is accruing patients, targeting completion and New Drug Application (NDA)
filing in 1999. We also expect to unblind our US Phase III trial for Topical
Panretin in KS in 4Q97 and, if positive, to file an NDA within two to three
months," he said.
Kaposi's Sarcoma (KS) Systemic Therapy
Interim results of the first 25 patients enrolled in the first stage of a
multicenter Phase II study of Oral Panretin in KS have shown an acceptable
safety profile and a sufficient number of positive responders according to the
study design. These results have prompted the AIDS Malignancy Consortium
(AMC) to proceed with full accrual of at least 55 total patients, according to
Steven Miles, M.D., Associate Professor of Medicine and Director of the UCLA
Clinical AIDS Research and Education (CARE) Clinic, and co-chairman of the
Phase II study. Dr. Miles presented this information to the AMC Steering
Committee in Bethesda, MD in April 1997.
"We are encouraged by the very manageable safety profile and the early
observations by investigators, who reported sufficient numbers of partial or
complete responses based on AIDS Clinical Trial Group (ACTG) criteria among
the first 25 patients enrolled to proceed with completion of patient accrual,"
Dr. Miles said.
In the AMC trial, patients with documented KS associated with HIV
infection received Oral Panretin at a dose of 60mg/m2 once daily and then were
advanced to 100mg/m2 once daily after two weeks if tolerance allowed. Some
patients received doses as high as 140 mg/m2/day. A similar trial conducted
by Ligand Pharmaceuticals Inc. on behalf of ALRT is also accruing patients.
Myelodysplastic Syndrome (MDS)
MDS is a premalignant blood condition with no effective treatment, except
for bone marrow transplantation in a small percentage of patients. An ongoing
study in MDS with 30 patients that have been treated according to an
intrapatient dose escalation scheme that ranged from 60 mg/m2 to 140 mg/m2
once daily with Oral Panretin in an open label study is being conducted at six
centers in the United Kingdom, Germany and France. One transfusion-dependent
patient had a complete normalization of peripheral blood counts and two others
had a decrease in red cell transfusion requirements. Additional responses may
yet be detected in 12 patients still on treatment between eight and 18 weeks.
Preliminary data from this trial are expected to be presented later this year.
Psoriasis
An ongoing multicenter Phase II dose response study in psoriasis shows
Oral Panretin is well-tolerated and appears to be effective in patients with
moderate to severe plaque psoriasis affecting greater than 20% of their body
surface area.
In this 50 patient study, 50% (5 of 10 patients) who received the optimal
dose level of 0.9 mg/kg administered daily, achieved a 50% or greater
improvement based on the Physician's Global Evaluation.
Dose response was seen through the 0.9 mg/kg dose level. A higher dose
of 1.2 mg/kg was nearly as effective but resulted in additional side effects,
such as headaches.
"This is the first study of Panretin in psoriasis, and we are encouraged
to see these initial efficacy results. Early data also indicate an acceptable
safety profile," said Erik Lippa, M.D., Director of Medical Affairs at
Allergan, Inc. (NYSE:AGN).
Renal Cell Carcinoma
Results from two multicenter Phase I/II studies of Oral Panretin in
combination with interferon alpha have led ALRT to discontinue further study
in this tumor type.
In Canada, a multicenter Phase I/II study of 38 patients explored Oral
Panretin at doses of 30 and 50 mg/m2 twice daily in conjunction with
interferon alpha given by daily subcutaneous injection. The dose of
interferon was escalated in each patient from 3 to 9 million International
Units (MIU) over a period of four weeks. Follow-up of each patient for
determination of response was a minimum of four months unless the patient
discontinued prior to that time. In the Phase I portion of the study,
15 patients were treated and the combination of 30 mg/m2 twice daily Oral
Panretin and 9 MIU interferon alpha daily by subcutaneous injection was
determined to be the maximum tolerated dose (MTD). In the Phase II portion of
the study, 23 patients were treated at MTD, 17 were evaluable for response.
There were no known objective responses in 11 patients evaluable for
response in the Phase I portion of the study, but 5 (45%) patients had
stabilization of disease for a median of 6.3 months. In the Phase II portion
of the study, there were no known objective responses but 11 (65%) of
17 evaluable patients had stable disease.
A multicenter U.S. trial of 59 patients using a similar design but
different doses of Oral Panretin and interferon did not produce any objective
responses. The MTD in the U.S. trial was 100 mg/m2 once daily Oral Panretin
and 5 MIU interferon alpha by subcutaneous injection three times per week.
Doses of 60 mg/m2 and 140 mg/m2 were also studied in the Phase I portion of
the trial. There were no objective responses in the Phase I portion of the
trial and none in the 34 patients who received the Phase II dose. Patients
continue to be followed on this trial including one patient who has been on
the study for more than one and one-half years. About 24% of all patients
were able to stay on study for four months or more.
"These results reinforce emerging data that, except in certain indications
such as APL and KS, Panretin does not act as a cytoreductive agent in advanced
cancers, but appears to stabilize the disease," said Steven D. Reich, M.D.,
Senior Vice President, Clinical Research at Ligand Pharmaceuticals Inc.
(Nasdaq: LGND). "Stabilization of disease progression using drugs with
gentler toxicity profiles than cytotoxic agents will continue to have clinical
benefit," he said.
Non-Hodgkin's Lymphoma
In a Phase II single center study, one out of 22 non-Hodgkin's lymphoma
(NHL) patients evaluable for response showed a partial response to Oral
Panretin. Patients with relapsed or refractory Ki-1+ anaplastic large cell
lymphoma, peripheral T-cell lymphoma, follicular small cleaved cell and mixed
cell, and small lymphocytic lymphoma were eligible. Patients must have failed
at least two treatment programs. The dose used in the study was 100 mg/m2 once
daily with the option to raise the dose to 140 mg/m2 should the patient
tolerate the lower dose. Treatment was to be given for a minimum of six weeks
for assessment of activity.
"Oral Panretin has activity in non-Hodgkin's lymphoma, but it is
insufficient to warrant further trials at this time," Dr. Reich said.
Multiple Myeloma
Based on an assessment of the data from the first 18 patients from a Phase
II single center study, investigators have now concluded that there is not
sufficient activity to justify further investigation of Oral Panretin in
multiple myeloma. No responses were observed in this study of previously
treated multiple myeloma that started patients at a dose of 60 mg/m2 daily and
allowed modification of dose, if tolerated, to 100 mg/m2 daily.
Background
Panretin is a proprietary product of Allergan Ligand Retinoid
Therapeutics, Inc., a company whose primary purpose is to discover and develop
drugs based on retinoids. Retinoids have a broad range of biological actions,
and evidence suggests that retinoids may be useful in the treatment of skin
diseases, metabolic diseases, a variety of cancers, including certain forms of
leukemia, as well as eye diseases.
This statement may contain certain forward looking statements by ALRT and
actual results could differ materially from those described as a result of
factors including, but not limited to, the following. There can be no
assurance Panretin, or any product in the ALRT pipeline, will be successfully
developed, that regulatory approvals will be granted, that patient and
physician acceptance of these products will be achieved, that final results of
human clinical trials will be consistent with any interim results, or that
final results will be supportive of regulatory approvals required to market
products. |
