BTECH REGULATORY RADAR - Tracking the Movement of Key Products Through Clinical Trials

UPGRADED TO PREGNANCY CATEGORY B

The FDA approved a less limiting pregnancy rating for AstraZeneca's (NYSE:
AZN) Pulmicort Turbuhaler (budesonide inhalation) based on data from three
Swedish birth registries. These data demonstrated that Pulmicort use during
early pregnancy was not associated with an increased risk of birth defects.
The data included use in approximately 2000 pregnancies from 1995-1997.
Pulmicort now has a pregnancy category B, rather than C, rating, the lowest
level of risk being an extremely rare "A." Dr. Michael Schatz, co-chair of
the pregnancy committee at the American College of Allergy, Asthma and
Immunology, pointed out that, "This doesn't mean that other inhaled steroids
are not safe.but at this point in time, only Pulmicort has the data."
However, his surprise that the FDA allowed the upgrade without a randomized,
controlled trial, as typically mandated for category B, was even mirrored by
the FDAs deputy director of the division of pulmonary and allergy drug
products, who nevertheless maintained that "Our view of these registries was
that the data was adequate to go to a category B." Pulmicort is an important
respiratory product indicated for the maintenance prophylaxis of asthma (as
opposed to acute care). Prescriptions for pregnant women in the U.S. are
likely to increase, and monitoring of these new patients will further
strengthen this trend if the data continue to be positive.

TO LAUNCH

Sanofi-Synthélabo (Paris: SASY) and Organon's (a division of Akzo Nobel,
NASDAQ: AKZOY) Arixtra is slated to be launched in late January with 240
sales reps. Promotions will highlight efficacy in studies versus Aventis'
(NYSE: AVE) Lovenox. A review of the anticoagulation market is available in
Btech Investor Reports: Out of the ASHes - The Resurrection of Anticoagulant
Therapy (December 18, 2001).

FDA APPROVED

Medtronic (NYSE: MDT) gained FDA approval for its ambitious CareLink
Network. CareLink is a monitoring and software package that allows
physicians to receive data via a Medtronic web site from patients who have
GEM II DR/VR implantable cardioverter-defibrillators (ICDs). Approximately
23,000 patients wear this brand of ICD. Medtronic hopes to receive
additional approvals for other ICDs, pacemakers, heart failure devices, and
other defibrillators it has on the market. Ten pilot centers will work with
Medtronic to assess the system. Commercial availability dates, cost, and
charge protocols have yet to be announced.

Medtronic also gained FDA approval for its Synergy Versitrel
neurostimulator, its third totally implantable version for chronic pain
treatment. Medtronic indicated that this one is about 20% smaller than the
smallest marketed Synergy neurostimulator and is designed for patients who
are not considered candidates for the larger device.

sNDA SUBMITTED

Ortho-McNeil (a Johnson & Johnson [NYSE: JNJ] company) filed an sNDA for
marketing approval of Levaquin (levofloxacin tablets / injection) for the
treatment of nosocomial (hospital-acquired) pneumonia. If approved, the
product would be the first of the newer generation respiratory
fluoroquinolones to be indicated for nosocomial pneumonia. Presently,
Levaquin is the only antibiotic indicated to treat community-acquired
pneumonia (CAP) due to penicillin-resistant S. pneumoniae, the most common
pathogen in CAP. The agent is also indicated to treat CAP caused by other
common pathogens, acute maxillary sinusitis, acute bacterial exacerbation of
chronic bronchitis, uncomplicated and complicated urinary tract infections,
acute pyelonephritis, and uncomplicated and complicated skin and skin
structure infections.

NDA SUBMITTED

Merck / Schering-Plough Pharmaceuticals (a joint cholesterol management
venture between Merck [NYSE:MRK] and Schering-Plough [NYSE:SGP]) announced
that a New Drug Application (NDA) was submitted for marketing approval for
Zetia (ezetimibe) tablets. Zetia is a cholesterol absorption inhibitor that
has demonstrated efficacy as monotherapy or in combination with statins for
the reduction of elevated cholesterol levels (hypocholesterolemia).

PHASE III RESUMPTION

BioCryst (NASDAQ: BCRX) began patient enrollment in a phase III clinical
trial with once-a-day orally administered peramivir (RWJ-270201), its
neuraminidase inhibitor for the treatment of influenza. The trial is
designed to assess the efficacy and safety of peramivir for the treatment of
acute influenza A and influenza B infections in otherwise healthy adults.
The primary efficacy endpoint is the length of time from the first dose to
the clinically significant relief of influenza symptoms. This trial was
initiated in February 2000 in Europe by The R.W. Johnson Pharmaceutical
Research Institute, and BioCryst has gained FDA approval to move forward in
the U.S. to complete it. The study is double-blind and is slated to enroll
approximately 1,300 healthy adults. To date, 1,036 patients have been
randomized to one of three treatment groups. Approximately 65 U.S. centers
are now open to enroll patients.

PHASE III SETBACK

Merck / Schering-Plough Pharmaceuticals reported that phase III clinical
trial results of a fixed-combination tablet containing loratadine, the
active ingredient in Schering-Plough's non-sedating antihistamine Claritin,
and montelukast sodium, the active ingredient in Merck's asthma medication
Singulair, did not demonstrate a statistically significant improvement in
the treatment of seasonal allergic rhinitis compared to each product
administered separately. These findings were unable to reproduce data
suggesting synergy of the separately administered agents published in the
Journal of Allergy and Clinical Immunology. The companies must now decide
whether to pursue further study, as it appears that their belief is that the
convenience gained by fixed-combination administration needs to be augmented
by true synergy, not just additive benefit, in order to achieve commercial
success given impending generic competition.

PHASE IIb INITIATED

Neurocrine Biosciences (NASDAQ: NBIX) and Taisho initiated the first of two
pivotal, randomized, double blind, placebo-controlled, multi-center
dose-ranging, phase IIb clinical trial of NBI-6024, a therapeutic vaccine,
in approximately 400 adult and adolescent patients with new onset type I
diabetes. Neurocrine hopes that successful completion of these two trials,
the second of which is slated to begin during 2002, will support regulatory
submission for the marketing of NBI-6024 for type I diabetes. This trial's
primary endpoint is to assess the effect of repeated administrations of
NBI-6024 in preserving endogenous insulin secretion as measured by C-peptide
levels in adult and adolescent patients with new onset type I diabetes.

PHASE II INITIATED

Abgenix (NASDAQ: ABGX) initiated a phase II clinical trial of ABX-EGF in
patients with prostate cancer. This fully human monoclonal antibody targets
the epidermal growth factor receptor (EGFr), a receptor identified on cells
of many solid tumor types. This multi-center, open-label trial is designed
to assess the safety and efficacy of ABX-EGF in patients with hormone
resistant prostate cancer without metastasis. It will enroll up to 50
patients who will receive intravenous infusions of 2.5 mg/kg of ABX-EGF
weekly over an 8-week treatment cycle, for up to 5 cycles. The study's
primary efficacy endpoint will be prostate specific antigen (PSA) response
rates (decrease of PSA level by greater than or equal to 50% compared to
baseline). Preliminary data from an ongoing, dose-escalating, phase I
clinical trial show that ABX-EGF is well tolerated and shows biological
activity at low doses. Though phase I trials are not powered to evaluate
efficacy, three patients in the trial, including one with prostate cancer,
have achieved stable or minor PSA response. Other ongoing phase II
investigation of ABX-EGF is in kidney cancer, non-small cell lung cancer,
and colorectal cancer. Abgenix is developing ABX-EGF in collaboration with
Immunex (NASDAQ: IMNX). In spite of the fact that ABX-EGF may work well in
combination with chemotherapy, most current ABX-EGF investigations are as a
single agent, presumably due to ImClone's (NASDAQ: IMCL) patents on the use
of anti-EGF monoclonal antibodies in combination with chemotherapy. ABX-EGF
is a fully human monoclonal that will compete with ImClone's Erbitux, also
an anti-EGF monoclonal whose BLA was rejected by the FDA last week.

PHASE II PROJECTED

Early clinical trial data generated by Amylin's (NASDAQ: AMLN) AC2993
(synthetic exendin-4) continue to support the development of its long-acting
release formulation, AC2993 LAR. Amylin announced more data that provides
guidance for an AC2993 LAR dose-rising, phase II study in people with type
II diabetes planned to commence in the first half 2002. Now, it has been
demonstrated that sustained circulating concentrations of AC2993 lowered
both pre-meal and post-meal glucose concentrations throughout the day. In
addition to the compelling phase I studies of AC2993 LAR , the potential
exists for continuous glucose lowering over 30 days without the risk of
hypoglycemia (low blood glucose). Moreover, in earlier investigation of
AC2993, the two highest dose levels not only suggested a magnitude of effect
that could meet the new glucose control guidelines recently outlined by the
American College of Endocrinology (ACE) and the American Association of
Clinical Endocrinologists (AACE), but also suggested that hypoglycemia risk
is minimal. If AC2993 and AC2993 LAR continue to perform well these agents
will compete with, and potentially complement, other agents in the bolus
and, especially, basal anti-diabetic marketplaces. Amylin's pipeline may
make it a strong player in the diabetes market, or a prime acquisition
target for the existing leaders in this market. Amylin's lead drug
candidate, Symlin (pramlintide acetate), is currently under regulatory
review by the FDA as a treatment for people with diabetes who use insulin.
The company is conducting additional clinical studies before submitting an
amendment to its NDA for Symlin in the second half of 2002. Amylin expects
that information from the investigations will fulfill the FDA's request for
additional clinical data as indicated in the Approvable Letter received in
October 2001 and in subsequent discussions with the FDA. For a review of
selected marketed and developmental diabetes products, please refer to Btech
Investor Reports: Inhaled Insulin, July 9, 2001 and Btech Investor Reports:
Recombinant Proteins, May 17, 2001.

IND SUBMITTED

AtheroGenics (NASDAQ: AGIX) filed an Investigational New Drug (IND)
application with the FDA for AGI-1096, a novel, oral drug for the prevention
of organ transplant rejection.

GRANTED ORPHAN STATUS

Transkaryotic Therapies' (NASDAQ: TKTX) iduronate-2-sulfatase (I2S) enzyme
replacement therapy for the treatment of Hunter syndrome, has been
designated an orphan drug in both Europe and the U.S. Typically products
with this designation that receive the first marketing approval for the
designated indication are entitled to a certain duration of market
exclusivity. The E.U. grants up to ten years of marketing exclusivity for
serious disorders affecting not more than 185,000 people and the U.S. grants
up to seven years exclusivity for disorders affecting less than 200,000
people.

INITIATING DEVICE TRIALS

Biocompatibles (London: BII) and British Biotech (NASDAQ: BBIOY) launched a
pivotal European trial designed to set the stage for marketing approval of
their drug-coated Batimastat BiodivYsio stent for reducing restenosis after
coronary angioplasty. Approximately 400 patients will participate in the UK,
France, Belgium, and Holland. The first patient was treated on December 24th
by Dr. Fajadet at the Clinique Pasteur in Paris. In December, the companies
also filed a request with the FDA to initiate a similar multicenter trial in
the United States. European trial results are expected later this year and
in 2003 in the United States. Batimastat is a matrix metalloproteinase
inhibitor, and is licensed to Biocompatibles by British Biotech. The coated
stent will be distributed in the United States by Abbott Laboratories (NYSE:
ABT). Matrix metalloproteinase inhibition has failed to demonstrate much
success in terms of diminishing angiogenesis to such an extent as to provide
clinical relief from metastatic cancer. However, since these molecules also
interfere with other, related, biological systems, the companies hope to
exploit the molecule's ability to interfere with the process of
extracellular matrix degradation and subsequent cell migration as well as
collagen deposition and vessel remodeling, rather than the growth of new
blood vessels, per se, that is implicated in restenosis.

BTECH NEWS
by Leon Henderson, M.D.
Bennett Weintraub, Ph.D.
Christopher Martin
www.btechnews.com
January 7, 2002

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BTECH NEWS, published by Btech Investor, Inc., highlights selected events in the life sciences sector that the Btech Investor team believes are particularly relevant to biotechnology investors. The Btech Investor team combines scientific, clinical, and business experience to perform comprehensive analysis of the biotechnology industry and to identify future industry leaders.

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The Btech Investor Reports provide in-depth analysis of the biotechnology industry. Recent companies profiled include Vertex, EntreMed, Élan, IDEC Pharmaceuticals, Myriad Genetics, and Abgenix. Recent sector reports include nucleic acid therapeutics, Alzheimer disease, inhaled insulin, recombinant proteins, gene therapy, monoclonal antibodies, neurodegenerative diseases, stem cells, trends in oncology, genomics based drug discovery, and biotech trends.

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