I'm don't know what direction the stock price will take, but if Genzyme's stock activity is any indication, it will go up.
Genzyme (genz) spun off its cancer treatment and diagnostic products into a separate tracking stock called gzmo on November 16th. That stock started trading separately as gzmo on Tuesday, November 16.
I believe the shorts will have to buy the new stock spin-off and I don't think they will be too anxious to do that, so they may cover before.
Agouron said they hoped to split the stock off in calendar 1998, if it is approved.
As they say, the sum of the parts is greater than the whole, at least for Genzyme.
Genzyme hit an all time high the day before the dividend (new stock) was distributed, and declined by less than the amount of gzmo the first day of trading, and genz has since made new highs. The previous high for genz was around 44. gzmo is around 4-5 today.
Of course, it's a different company and you can't compare but at least it gives a very recent example of what happened to another biotech under similar circumstances.
Agouron's estimated earnings will be much higher, after the spin-off since 25% of R&D costs and SG&A expenses will belong to the new stock. That should lead to revised earnings estimates, upwards and should help the stock price.
Agouron's new stock will also be a tax-free dividend.
<<Genzyme General Corp. Monday said shares of its unit Genzyme Molecular Oncology will trade on Nasdaq under the GZMO starting on Tuesday.
''In addition, Genzyme Molecular Oncology shares will be distributed today as a tax-free dividend to Genzyme General shareholders of record as of November 2,
Genzyme Molecular Oncology develops cancer treatments and diagnostic products.
''Genzyme Molecular Oncology has its own common stock intended to reflect its economic value and track its performance,'' the statement said.>>
As far as IL-2 in combination with HAART. It is not a cure. It's function in the studies is to activate the resting cells that contain HIV virus in the "hidden reservoirs"
IL-2 has been around since 1984 or so, and if it was that good, I would think it would be more widely used. I looked it up on Chiron's site, and was surprised to see how toxic it is, and how many serious side effects there are. It makes me wonder about the physicians who criticize protease inhibitors and the side effects, when it is still unknown how much of lipodystrophy or lipid/insulin disorders are due to protease inhibitors.
There is no controversy about the side effects of IL-2. Apparently there are less side effects wih IL-2 if administered subcutaneously, than through IV.
chiron.com (requires Adobe Acrobat)
Fauci and others use IL-2 to activate the resting cells in reservoirs that contain HIV virus, so that HAART can then destroy them. But it still has to given for months or a year and has many serious side effects. And no one thinks that this will be a cure. There will be remaining HIV virus in certain compartments or sanctuaries that IL-2 will not reach: macrophages, brain, CD4+ T cells in the gut and other places etc.
So IL-2 may be reduce or eliminate the virus only in certain areas but something is still needed, like Remune -a substance to stimulate the immune system to control whatever virus remains and to stimulate the CTL's, an anti-HIV specific proliferative response.
______________________________________________
Here are some notes from Jules Levin, from the Glasgow meeting.
Thu, 12 Nov 1998 ,
Remune+HAART
<<At the Agouron Symposium today, Guiseppe Pantaleo an immunologist at Beaumont
Hospital in Lausanne Switzerland and Ronald Mitsuyasu an immunologist at UCLA
gave a very nice overview of HIV and the immune system. They discussed how
HAART improves the immune system and in what ways HAART does not improve the
immune system. Upon return to NYC I hope to report their presentations. A you
may know Fred Valentine an immunologist from NYU reported in Geneva that after
a month on HAART Remune, a therapeutic HIV vaccine, was administered to study
participants with chronic HIV infection. Previously it was doubted that a CD4
response to HIV antigens could be mounted by individuals with chronic
infection. Bruce Walker had detected such a response by treating individuals
in acute infection with HAART. In Valentine's study a strong HIV specific CD4
response was detected following HAART+Remune. Several weeks ago Agouron
reported that at week 32 13/15 participants had <1 copy/ml, while 6/12 in the
control group who received IDV+2 NRTIs had <1 copy/ml. The baseline viral load
was only 8000 copies/ml.>>
<<A number of studies are being designed to explore the use of Remune+HAART. The
goal is to see if the immune system can be stimulated to the extent that it
might control HIV replication with HAART than HAART alone. Another goal is to
see if Remune+HAART can control the immune system enough so that a person
could stop HAART. In the Valentine study almost 90% responded to Remune+HAART.
Company officials said at this meeting that it can take longer than 32 weeks
for some individuals to respond to Remune. I told company officials at this
meeting that they need to explore HAART+Remune in two populations--individuals
with low CD4s, and individuals who had low CD4s and increased their CD4s due
to HAART.>>
<<A lot of attention is being paid to developing Remune and to developing other
immune based therapies as adjuncts to HAART. The ACTG is planning several
studies, one of which may explore using IL-2 plus Remune with HAART.
IL-2+HAART is also being explored. As well, other immune based therapies are
being researched.>>
I just got these notes, some preliminary data using Crixivan (1250 mg) and Nelfinavir (1250) twice a day.
From the aegis mail list.
"The pharmacokinetic analysis showed that the twice-daily dural combination
of Crixivan 1,200 mg with nelfinavir 1,250 mg achieved blood levels of
Crixivan comparable to the blood levels seen in the approved dosing regimen
of Crixivan 800 mg every eight hours. Crixivan did not affect the
pharmacokinetic profile of nelfinavir.
<<The pharmacokinetic analysis showed that the twice-daily dual combination of
Crixivan 1,200 mg with nelfinavir 1,250 mg achieved blood levels of Crixivan
comparble to the blood levels seen in the approved dosing regimen of
Crixivan 800 mg every eight hours. Crixivan did not affect the
pharmacokinetic profile of nelfinavir.
<<The double protease-inhibitor regimen reduced viral load to less than 400
copies/mL in 77 percent (10/13) of the patients remaining in the study at
week 68, and to less than 50 copies/mL in 8 of 9 patients who were evaluated
using an ultra-sensitive assay at week 64. Patients' baseline edian viral
load was 50,500 copies/mL. Patients' CD4 counts increased from baseline by
a median of 334 cells/mm3. The median CD4 count at baseline was 259
cells/mm3.
<<The combination was generally well-tolerated. Adverse
events included rash, diarrhea, bloating/cramps, nausea and
nephrolithiasis.>>
As far as side effects of IL-2, here are a few. There are many more described on Chiron's home page.
<<PROLEUKIN, a lymphokine, is produced by recombinant DNA technology using a
genetically engineered E. coli strain containing an analog of the human interleukin-2 gene.
It is approved by the FDA for treatment of metastatic melanoma and renal cell carcinoma.
<<In vitro studies performed on human cell lines demonstrate the immunoregulatory properties of
PROLEUKIN, including: a) enhancement of lymphocyte mitogenesis and stimulation of long-term growth of
human interleukin-2 dependent cell lines; b) enhancement of lymphocyte cytotoxicity; c) induction of killer cell
(lymphokine-activated (LAK) and natural (NK)) activity; and d) induction of interferon-gamma production.>>
<<Because of the severe adverse events which generally accompany PROLEUKIN (aldesleukin) therapy at the recommended dosages, thorough clinical evaluation should be performed to identify patients with significant cardiac, pulmonary, renal, hepatic, or CNS impairment in whom PROLEUKIN is contraindicated. >>
<<Patients with normal cardiovascular, pulmonary, hepatic, and CNS function may experience serious, life threatening or fatal adverse events. Adverse events are frequent, often serious, and sometimes fatal.>>
<<Should adverse events, which require dose modification occur, dosage should be withheld rather than reduced>>
<<These effects include activation of cellular immunity with profound
lymphocytosis, eosinophilia, and thrombocytopenia, and the production of cytokines including tumor necrosis factor, IL-1 and gamma interferon.>>
<<PROLEUKIN should be administered in a hospital setting under the supervision of a qualified physician
experienced in the use of anticancer agents. An intensive care facility and specialists skilled in cardiopulmonary
or intensive care medicine must be available.>>
PROLEUKIN administration has been associated with capillary leak syndrome (CLS) which is characterized by a loss of vascular tone and extravasation of plasma proteins and fluid into the extravascular space.
CLS results in hypotension and reduced organ perfusion which may be severe and can result in death.
Associated with cardiac arrhythmias (supraventricular and ventricular), angina, myocardial infarction, respiratory
insufficiency requiring intubation, gastrointestinal bleeding or infarction, renal insufficiency, edema, and mental
status changes.
PROLEUKIN treatment is associated with impaired neutrophil function (reduced chemotaxis) and with an
increased risk of disseminated infection, including sepsis and bacterial endocarditis. Consequently, preexisting
bacterial infections should be adequately treated prior to initiation of PROLEUKIN therapy. Patients with
indwelling central lines are particularly at risk for infection with gram positive microorganisms. Antibiotic
prophylaxis with oxacillin, nafcillin, ciprofloxacin, or vancomycin has been associated with a reduced incidence
of staphylococcal infections.
PROLEUKIN administration should be withheld in patients developing moderate to severe lethargy or
somnolence; continued administration may result in coma.
PROLEUKIN has been associated with exacerbation of pre-existing or initial presentation of autoimmune
disease and inflammatory disorders. Exacerbation of Crohns disease, scleroderma, thyroiditis, inflammatory
arthritis, diabetes mellitus, oculo-bulbar myasthenia gravis, crescentic IgA glomerulonephritis, cholecystitis,
cerebral vasculitis, Stevens-Johnson syndrome and bullous pemphigoid, has been reported following treatment
with IL-2.
All patients should have thorough evaluation and treatment of CNS metastases and have a negative scan prior to
receiving PROLEUKIN therapy. New neurologic signs, symptoms, and anatomic lesions following
PROLEUKIN therapy have been reported in patients without evidence of CNS metastases. Clinical
manifestations included changes in mental status, speech difficulties, cortical blindness, limb or gait ataxia,
hallucinations, agitation, obtundation, and coma. Radiological findings included multiple and, less
commonly, single cortical lesions on MRI and evidence of demyelination. Neurologic signs and symptoms
associated with PROLEUKIN therapy usually improve after discontinuation of PROLEUKIN therapy; however,
there are reports of permanent neurologic defects. One case of possible cerebral vasculitis, responsive to
dexamethasone, has been reported. In patients with known seizure disorders, extreme caution should be
exercised as PROLEUKIN may cause seizures.
Capillary leak syndrome (CLS) begins immediately after PROLEUKIN (aldesleukin) treatment starts and is marked by increased capillary permeability to protein and fluids and reduced vascular tone. In most patients, this results in a concomitant drop in mean arterial blood pressure within 2 to 12 hours after the start of treatment. With continued therapy, clinically significant hypotension (defined as systolic blood pressure below 90 mm Hg or a 20 mm Hg drop from baseline systolic pressure) and hypoperfusion will occur. In addition, extravasation of protein and fluids
into the extravascular space will lead to the formation of edema and creation of new effusions.
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