Containing Campath Strategy BioCentury,

BioCentury,
THE
BERNSTEIN R EPORT
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AUGUST 27 , 2012
P AGE A7 OF 18
Strategy
Containing Campath
By Erin McCallister
According to the National Cancer Institute (NCI), about
Senior Writer
16,000 patients will be diagnosed with CLL in the U.S. this year.
Sanofi and its Genzyme Corp. subsidiary are not comHowever, the cancer drug is only used first line in the 10% of
pletely withdrawing alemtuzumab from the market, but they are patients with the 17p deletion, according to Brian Hill, an
making it harder for doctors to use the drug for its approved use, oncologist in the department of hematologic oncology and blood
chronic lymphocytic leukemia, and nearly impossible to use off disorders at the Cleveland Clinic.
label for multiple sclerosis.
He said Campath is used so narrowly because of its safety
In its 1H12 earnings, Sanofi disclosed it would withdraw profile and its efficacy in this subgroup.
alemtuzumab from the market for CLL. On Aug. 8, the European
Campath’s label carries a boxed warning about the risk of
Commission issued a decision to withdraw the marketing autho- cytopenias, infusion reactions and infections. In the Phase III trial
rization for MabCampath in Europe. Withdrawal in the U.S., in 147 treatment-naïve patients, 97% reported grade 3 or 4
where the drug is sold under the name Campath, will be effective lymphopenia and 42% reported grade 3 or 4 neutropenia.
Sept. 4.
Additionally, 55% of patients experienced CMV viremia, and
Going forward, Sanofi and Genzyme
16% of patients had CMV infections. About
will to provide Campath free of charge to
10% of patients experience grade 3 or 4
“I wasn’t surprised that they
oncologists for CLL and a handful of offpyrexia and/or chills associated with infulabel indications through a patient access
sion of Campath.
took it off the market. It is
program, which has already started in
According to Hill, standard of care
being relaunched in a
Europe.
fludarabine typically produces only a 30%
In a written statement, the pharma told
response rate in CLL patients with the 17p
different context, a different
BioCentury it has decided “to focus on
deletion.
patient population and a
bringing alemtuzumab forward for MS,”
In a subgroup of treatment-naïve paand that restricting access will help pretients with 17p deletions in the Phase III
different dose.”
vent off-label use of the drug in this inditrial, Campath resulted in median procation.
gression-free survival (PFS) of 10.7 vs. 2.2
Steven Krieger, Mount Sinai
In June, Genzyme and Sanofi submitted
months for control and response rates of
Medical Center
applications to FDA and EMA to market
64% for Campath and 20% for control.
alemtuzumab for MS under the name
According to Howard Ozer, chief of
Lemtrada.
hematology/oncology and interim director of the University of
Oncologists contacted by BioCentury were disappointed by Illinois Cancer Center, Campath also is used in heavily
the decision, but generally don’t believe it will negatively affect refractory patients.
patients as long as the access program isn’t too onerous.
“Patients who are completely refractory to other treatments
Neurologists weren’t bothered by Genzyme’s decision and can benefit from Campath and doctors like having the drug
believe blocking off-label use will prevent safety issues from available as an option. Loss of the drug would not be a good
arising while the Lemtrada applications are under review.
thing,” he said.
Meanwhile, the move offers financial upside for holders of the
According to Genzyme spokesperson Bo Piela, the company
Genzyme CVR. Sanofi acquired the biotech in 2011 for about started informing U.S. doctors of the impending withdrawal of
$20.1 billion plus a $14 contingent value right, $12 of which is Campath and the patient access plan in July and European
tied to sales milestones for Lemtrada for MS.
doctors earlier this month.
Off-label use of Campath would be cheaper than Lemtrada,
He said physicians in the U.S. and Europe will be able to
which is likely to be priced competitively with other MS drugs. request Campath/MabCampath on a per patient basis.
Physicians will need to complete a product request form
indicating basic patient information, the intended use, the
Cancer OK
number of vials requested and agree to the terms and conditions
Alemtuzumab is a humanized mAb against CD52. The mAb of the program.
“If the request falls outside of predefined criteria, physicians
binds the target, which is present on the surface of B and T
lymphocytes, and causes the cells to undergo antibody-depen- may also be asked to complete a medical review form to
document the clinical rationale for the intended treatment,” Piela
dent cell-mediated lysis and die.
For CLL, which is associated with an increase in B lympho- said.
He added the program also will make the drug available for
cytes, alemtuzumab destroys the excess B cells.
In MS, alemtuzumab is believed to exert its therapeutic effects certain off-label malignancies for which conventional therapies
by depleting T and B cells that may be responsible for cellular have failed, are unsuitable or unavailable.
The drug will also be provided for hematopoietic stem cell
damage.
In 2001, alemtuzumab was approved in the U.S. and Europe transplant conditioning and solid organ transplant at institutions
to treat B cell CLL in patients previously treated with alkylating that have documented protocols.
Alemtuzumab will be available for MS patients only within the
agents and who have failed fludarabine therapy. Campath was
See next page
approved as a first-line treatment in the U.S. in 2007.
BioCentury,
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THE
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neurology at Mount Sinai Medical Center, wasn’t surprised by Genzyme’s decision.
clinical trial setting, Piela said.
“I wasn’t surprised that they took it off
While doctors said they were assuaged
the market. It is being relaunched in a
by Sanofi and Genzyme’s plan to provide
different context, a different patient poputhe drug under the patient access prolation and a different dose,” he said.
grams, some physicians are concerned
Edward Fox, a neurologist at Central
Til Menge, University Hospital
that the additional work could deter use of
Texas Neurology Consultants and a
Dusseldorf
Campath.
PI in the Phase II trials for alemtuzumab for
“Restricted access is always concernMS, believes that once the Phase III results
ing and the addition of more paperwork can create a lag time,” are published in scientific journals, off-label use could have been
said Javier Pinilla-Ibarz, a hematologic oncologist at H. Lee expected to increase.
Moffitt Cancer Center & Research Institute. Nevertheless,
“I think once data is published that spells out how alemtuzumab
he said, “I don’t think lag times will prevent its use among the can be given in MS, the chance of off-label use goes up
majority of clinicians.”
dramatically. The concern is that the company and FDA have not
Matthew Davids, an instructor and attending physician in the instituted any sort of risk management system,” he said.
lymphoma group at Dana-Farber Cancer Center, noted that
Krieger agreed.
larger research institutes have more experience in dealing with
“I think now that the Phase III trials and data are public and
special access programs like the one Sanofi and Genzyme are as publications come out detailing the data, there will surely be
proposing and may be more immune to any potential obstacles. an interest. But with the drug under FDA review that is not the
Nonetheless, he also believes most doctors will still use the best time to experiment with it,” he said.
drug.
Krieger added: “This is the time to expectantly wait to see
“I don’t think the paperwork burden will be huge. It is an what FDA rules and if they approve it, how the drug should be
important drug for those patients in which it works, so motiva- monitored and how to achieve the best benefit to risk profile.”
tion is on the clinician’s side to get patients the drug,” Davids
Genzyme would not disclose whether the company has
said.
submitted or FDA has requested a REMS for Lemtrada. The
company submitted its sBLA in June.
Even if data are published, Til Menge, a neurologist at
However, Thomas Elter, a physician in the department of
Hematology and Oncology at the University of Cologne, University Hospital Dusseldorf, believes doctors will rehasn’t yet used MabCampath since the program started in main hesitant to use alemtuzumab off label because of the mAb’s
safety.
Europe.
Elter said Genzyme told him it should take no more than two
“Given the known safety profile of alemtuzumab, I think MS
weeks to receive the drug, although Piela told BioCentury it doctors will be reluctant to use it off label,” he said.
should take no more five days from when a request is submitted
In the Phase III CARES-MS trial of 840 patients with relapsingremitting MS (RRMS) who relapsed while receiving beta interto when the drug is shipped to the physician.
In any case, Elter estimated it takes physicians about 30 feron or Copaxone glatiramer acetate, about 16% of Lemtrada
patients developed an autoimmune thyroid-related adverse event
minutes to fill out the paperwork, which is too long for him.
“Before, it took just seconds between when I would prescribe and about 1% developed immune thrombocytopenia.
The rates of immune AEs were not reported for the active
the drug and could have access to it. But now it will take just a
half hour to fill out the paper work. I don’t have a half an hour, control arm of Rebif interferon beta-1a.
Teva Pharmaceutical Industries Ltd. markets Copaxone.
so to save my time I will look for an alternative,” he said.
According to Elter, other options could include enrolling CLL Merck Serono S.A., a division of Merck KGaA, markets Rebif
with Pfizer Inc.
patients with the 17p deletion in a clinical trial.
Piela said that Genzyme is “hoping to implement online forms
in the future.”
On Friday, the Arzneimittelkommission der deutschen Covering the CVR
Arzteschaft (AkdA) released a statement calling Genzyme
Campath is distributed in a 1-mL vial of 30 mg/mL. The
and Sanofi’s decision purely commercial and said the volun- recommended dose for CLL is 30 mg/day three times per week
tary withdrawal unnecessarily complicates cancer treatment. for 12 weeks.
AkdA is the Drug Commission of the
According to Genzyme, the annual
Bundesarztekammer, the German
treatment cost for Campath is about
Medical Association.
$60,000 per patient. Assuming one 12“It is an important drug for
week course per year, the per dose price
those patients in which it
of Campath is about $1,666.67.
Off label, off limits
In the Phase III trials for Lemtrada, the
works, so motivation is on
While most MS doctors contacted by
mAb was dosed at 12 mg per day on the
the clinician’s side to get
BioCentury haven’t used Campath off lafirst five days of the trial. The patients
bel, they believe the decision to withdraw
were dosed again a year later with 12 mg
patients the drug.”
was a good one and could prevent potenper day for three days for a total of 8
tial safety issues from arising while the
doses.
Matthew Davids,
drug is under review.
MS doctors using Campath off label
Dana-Farber Cancer Center
See next page
Steven Krieger, assistant professor of
“Given the known safety
profile of alemtuzumab,
I think MS doctors will be
reluctant to use it off label.”
BioCentury,
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AUGUST 27 , 2012
P AGE A9 OF 18
The next $10 includes payments of $3 if net sales of Lemtrada
total $1.8 billion over four quarters, $4 for sales of $2.3 billion
over four quarters and $3 for sales of $2.8 billion.
according to the Lemtrada dosing schedule would only use 96 mg
of the CLL drug over two years for a total treatment cost of
$6,666.68.
The off-label cost of Campath for MS is considerably lower
than other MS drugs.
For example, the average wholesale cost of Tysabri natalizumab
is $4,576.37 for a 15-mL vial of 20 mg/mL. With a recommended
dose of 300 mg every four weeks, the annual cost of Tysabri is
about $59,375.81.
Biogen Idec Inc. and Elan Corp. plc market Tysabri.
If Genzyme and Sanofi plan to price Lemtrada competitively
with other MS drugs, doctors could use Campath off label at a
lower cost, which would be bad news for holders of the Genzyme
CVRs.
In 2011, Sanofi acquired Genzyme for about $20.1 billion
plus the $14 CVR, $13 of which is tied to milestones for Lemtrada
for MS (see BioCentury, Feb. 21, 2011).
The first CVR milestone for Lemtrada is $1 for FDA approval.
The next $2 Lemtrada milestone will trigger if net sales over four
quarters exceed $400 million.
COMPANIES AND INSTITUTIONS MENTIONED
Biogen Idec Inc. (NASDAQ:BIIB), Weston, Mass.
Bundesarztekammer, Berlin, Germany
Central Texas Neurology Consultants, Round Rock, Texas
Cleveland Clinic, Cleveland, Ohio
Dana-Farber Cancer Center, Boston, Mass.
Elan Corp. plc (NYSE:ELN), Dublin, Ireland
Genzyme Corp., Cambridge, Mass.
H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla.
Merck KGaA (Xetra:MRK), Darmstadt, Germany
Mount Sinai Medical Center, New York, N.Y.
National Cancer Institute (NCI), Bethesda, Md.
Pfizer Inc. (NYSE:PFE), New York, N.Y.
Sanofi (Euronext:SAN; NYSE:SNY), Paris, France
Teva Pharmaceutical Industries Ltd. (NYSE:TEVA), Petah Tikva,
Israel
University Hospital Dusseldorf, Dusseldorf, Germany
University of Cologne, Cologne, Germany
University of Illinois Cancer Center, Chicago, Ill.
Featured links this week
Links to the following documents reside online on the BioCentury on
BioBusiness page of www.biocentury.com.
Antibiotics
NICE guidance on use of antibiotics to prevent and treat early
onset neonatal infection.
Stem cells
U.S. Court of Appeals for the District of Columbia Circuit ruling
that upheld a lower court’s 2011 dismissal of a suit claiming NIH
violated a law prohibiting federal funds for research in which a
human embryo is destroyed (see BioCentury Extra, Friday, Aug. 24).
Venture tax
CalPERS
California Public Employees’ Retirement System (CalPERS) fiveyear strategic plan for meeting the retirement and health benefits
needs of its members.
European Commission public consultation seeking evidence of
direct tax problems that arise when venture capital is invested
across borders and possible solutions; comments are due Nov. 5.
Product documentation
Devices
Registration for the Aug. 30 FDA workshop to discuss
postapproval studies for class III devices regulated under PMA
regulations (see BioCentury Extra, Monday, Aug. 20).
IOM
Institute of Medicine summary of a June workshop to discuss
implementation of the Cures Acceleration Network (CAN), a
program that will allow NIH to fund R&D at biopharma
companies.
JOBS Act
SEC FAQ on research provisions in Title I of the Jumpstart Our
Businesses Startups (JOBS) Act.
NIH
NIH policy to give extra scrutiny to grant applications from
researchers who already receive $1 million or more per year
under active NIH awards (see BioCentury Extra, Wednesday,
Aug. 22).
‘It’s the BioCentury’TM
— Avastin: NICE final guidance recommending against Avastin
bevacizumab in combination with capecitabine for first-line
treatment of metastatic breast cancer; from the Genentech Inc.
unit of Roche (SIX:ROG; OTCQX:RHHBY).
— Alimta: CHMP revised EPAR updating SPC to include anaphylactic shock as an adverse reaction for Alimta pemetrexed to
treat pleural mesothelioma and non-small cell lung cancer
(NSCLC); from Eli Lilly and Co. (NYSE:LLY).
— Humira: Briefing documents for the Aug. 28 meeting of the
Gastrointestinal Drugs Advisory Committee to discuss an sBLA
for Humira adalimumab to treat moderately to severely active
ulcerative colitis in adults who failed conventional therapies;
from Abbott Laboratories (NYSE:ABT) and Eisai Co. Ltd.
(Tokyo:4523; Osaka:4523) (see BioCentury Extra, Friday, Aug. 24).
— Xgeva: NICE final appraisal determination (FAD) recommending the use of Xgeva denosumab to prevent skeletal-related
events (SREs) in patients with bone metastases from breast
cancer and from solid tumors other than breast and prostate
cancer for whom zoledronic acid would be indicated; and against
use in patients with hormone-refractory prostate cancer (HRPC);
from Amgen Inc. (NASDAQ:AMGN).