Spotlight On... Multiple Sclerosis, Sep. 2010 -- Pharma Matters Report

Image CopyrIght: REUTERS/Tim Wimborne

Spotlight on...
Multiple ScleroSiS
A phArMA MAtterS report.
JULY-SEPTEMBER 2010

Expert therapy area review of the key market players and
deals highlights for leading areas of industry investment
and development. These insightful reviews are based on
the strategic data and insights from Thomson Pharma® and
Thomson Pharma® Partnering Forecast.

AWARDED TO THOMSON SCIENT FIC LIMITED
(THE SCIENTIFIC BUS NESS OF THOMSON REUTERS)

ABSTRACT
Oral drugs will soon revolutionize treatment of multiple sclerosis. Until
recently, the only disease-modifying agents available were the interferons,
a highly competitive drug class, but with the disadvantage of administration
by injection. This report observes how this key drug franchise is evolving,
and evaluates the strengths and weaknesses of the current and future
players. Development of the deals landscape during this time of change
is discussed, highlighting recent activity as industry heavyweights pair up
for commercialization of the leading products, but also make significant
investments in developmental candidates that show promise. Extracting
consensus data from Thomson Pharma® Partnering Forecast, the report
assesses the present market and reveals the future dynamics and
competitive positioning of therapeutics in this exciting therapy area as it
diversifies and transforms.

Sales figures are correct as of July 16, 2010
For more information on Thomson Pharma and Thomson Pharma Partnering
Forecast visit go.thomsonreuters.com/commercial or email
scientific.lifesciences@thomsonreuters.com

PHARMA MATTERS | SPOTLIGHT ON... MULTIPLE SCLEROSIS

SECTION I
AN EvOLvING MULTIPLE SCLEROSIS MARkET:
THE ORAL REvOLUTION
With impending launches of the first oral drugs for multiple sclerosis
(MS), the MS market is entering an exciting phase of evolution, which will There has been a significant expansion of the
significantly impact patients’ lives and transform the competitive landscape MS market, driven primarily by price increases,
of this therapy area. new patient diagnoses in the US, and by
higher penetration rates in EU markets.
Since 1993, the only disease-modifying options for MS have been a range
of interferon-based products, which are administered intravenously,
intramuscularly or subcutaneously, typically with considerable discomfort.
Competition has been intense between the interferon products, and was
compounded by the entry of two new injectable therapies (Copaxone and
Tysabri) over the last decade. Competition across the market is now expected
to further escalate as the race for the first oral MS drug approval intensifies.
According to Thomson Pharma Partnering Forecast, the MS market is set
to rise from $8.9 billion in 2008, to $15.6 billion in 2014, based largely on
the expected entry of several new oral therapy options, although the beta
interferon brands and Tysabri will also see some growth.
This rapidly evolving market is also expected to further diversify as companies
with no previous involvement enter the sector. The MS market until now has
been dominated by an oligopoly; Biogen Idec, Teva, Merck Serono and Bayer
Schering have been the leading competitors globally. However, companies
like sanofi-aventis, AstraZeneca, Novartis and Glenmark, with some of
the most technologically advanced products in their pipeline portfolio, are
expected to start to attract the most investor attention as the market begins
to change. Indeed, Novartis is employing several strategies to enter the field
of MS therapeutics, including in-house development, early- to mid-stage
partnering, and development of biosimilars.

MULTIPLE SCLEROSIS WORLDWIDE (US$) 2008 REPORTED SALES

AvONEx 25%
REBIF 22%
NATALIZUMAB 9%
GLATIRAMER ACETATE 25%
BETASERON 19%

MULTIPLE SCLEROSIS WORLDWIDE (US$) 2014 CONSENSUS FORECASTS
BETASERON 9%
AvONEx 15%
ALEMTUZUMAB 2%
REBIF 14%
NATALIZUMAB 9%
GLATIRAMER ACETATE 26%
FINGOLIMOD 7%
FAMPRIDINE
(ORAL, SUSTAINED RELEASE,
MS / SPINAL CORD INjURy,
ACORDA/BIOGEN 6%
ExTAvIA 2%
CLADRIBINE (ORAL, MS),
MERCk SERONO 3%
OTHER 7%


MULTIPLE SCLEROSIS: THE CURRENT MARkET
The MS market has changed very little over the past 10 years. Four
There is a demand for oral therapy given
injectable disease-modifying drugs monopolized the landscape, with three
the inconvenience of dosing of existing
formulations of beta interferon (Biogen Idec’s Avonex, Merck Serono’s Rebif,
injectable therapies.
and Bayer/Novartis’ Betaseron) and one complex immunomodulatory
peptide (Teva’s Copaxone).
Copaxone became the best selling MS drug in 2008, driven primarily by the
drug’s tolerability and status as the only non-interferon front-line agent.
Copaxone gained its dominant market share largely through data from the
REGARD and BEyOND trials, which supported efficacy equal to that of the
interferons, without the associated tolerability issues.
In july 2008, Momenta/Sandoz and Mylan filed ANDAs for Copaxone,
which are currently being litigated and could threaten sales going forward.
Copaxone is a mixture of chemically synthesized polypeptides, and although
not approved as a biologic, because the multiepitopic sequences in
Copaxone are not completely characterized, Teva has argued that biosimilar
manufacturers will not be able to demonstrate their drug is a precise copy
of Copaxone. Although the FDA considers these contentions unpersuasive,
Copaxone is not expected to lose its bestseller position until 2013, even
as the market starts to radically diversify with the expected entry of oral
therapies in 2010. Even in the face of this competition, sales for Copaxone
are expected to rise from $2.26 billion in 2008 to $3.872 billion in 2013.
Avonex had been the best-selling MS drug until 2008, but despite being
overtaken by Copaxone, it still remains the top-selling interferon, having
performed well in the face of competition from the higher-dose interferons.
Steady market share and aggressive US pricing are supporting moderate
sales growth, and the product is expected to maintain its number one
interferon product status to 2013, with sales rising from $2.03 billion in
2008 to $2.342 in 2013. In a further effort to support the franchise, Biogen
Idec is also developing PEGylated Avonex, which prolongs the drug’s half-
life and improves its ease of use to twice-monthly injections; phase III trials
are ongoing.
Despite Avonex’s status as the top interferon, Rebif is the fastest-growing
interferon product in the franchise. Sales grew 15% in 2008 to $1.958 billion,
although the total was impacted by currency. Rebif has benefited from data
from the EvIDENCE trial, which established superiority for high-dose Rebif
over Avonex over 12 months. According to Thomson Pharma Partnering
Forecast, Rebif will see continued strongest growth within the three
interferon products in the period up to 2013, rising to $2.183 billion.

REPORTED AND CONSENSUS FORECAST REvENUE (MILLION US$)

Copaxone Avonex Rebif Betaseron

4000

3500

3000
SALES IN US $

2500

2000

1500

1000 2008 2009 2010 2011 2012 2013 YEAR*

REPORTED CONSENSUS

* Data is derived from Thomson Pharma Partnering Forecast


TYSABRI: GAINING MARkET SHARE,
BUT PML RISk SIGNIFICANT
In late 2004, Biogen Idec and partner Elan received first approval for Tysabri
in the treatment of MS. Seemingly destined for blockbuster status, the
drug’s commercialization was halted less than three months into its launch
following two cases of severe progressive multifocal leukoencephalopathy
(PML) reported in clinical trial patients treated with a combination of
Tysabri and Avonex for more than two years. A third confirmed case was
then reported in a Crohn’s disease patient receiving intermittent Tysabri
monotherapy over 18 months. At that time, Biogen Idec and Elan completed
a full review of Tysabri’s safety throughout its entire clinical trial program
and found no additional cases of PML in 3000 patients who had received
the drug.
Tysabri remained withdrawn from the market until further analyses
had been presented to the FDA, at which point a positive FDA panel
recommendation led to its relaunch in the US in july 2006, under the
TOUCH risk management program. The FDA had reviewed the impressive
efficacy data for Tysabri, and concluded the risk/benefit was acceptable
when other therapies had failed.
The drug’s approval was based upon data from the AFFIRM (Tysabri
monotherapy versus placebo) and SENTINEL (Tysabri plus Avonex
combination versus Avonex) studies. In these trials, Tysabri induced
a dramatic reduction in relapse rate versus either placebo or Avonex
monotherapy. In AFFIRM, patients experienced a 66% reduction in relapse
rates after one year, with annualized relapse rates of 0.25 for Tysabri versus
0.74 on placebo. At two years, AFFIRM demonstrated a 42% reduction
in the risk of disability progression for the Tysabri treatment arm versus
placebo, eclipsing reported risk reductions for Avonex (37% reduction) and
Rebif (30% reduction), while Betaseron and Copaxone have never shown an
impact on disease progression.
Since its relaunch, Tysabri has steadily gained market share, and the
drug surpassed $1 billion in sales for the first time in 2009. By june 2010,
regulators had linked the drug to 11 deaths and 55 cases of PML since it was
reintroduced in 2006, although were still recommending it remain on the
market. However, the drug’s sales will inevitably be closely linked to its rate
of association with PML, and another 12 months of commercial experience
may be required before Tysabri’s true association with PML becomes clearer,
possibly with data from the TyGRIS trial. In the meantime, Biogen Idec is
Avonex, with its convenient dosing and lower
evaluating whether earlier diagnosis followed by plasma exchange might
side effects, may benefit from a large-scale
improve patient outcomes, and is also seeking to identify factors that might
phase III trial examining the combined use of
predispose certain patients to PML. Sales are forecast to rise from $831
Avonex and Copaxone that is due to complete
million in 2008 to $1.517 billion in 2013, according to Thomson Pharma
in july 2012.
Partnering Forecast, which could be its peak year of sales.


THE FIRST ORAL THERAPIES
Despite the relative lack of options for MS over the last decade, significant
Rebif is clinically superior to Avonex after 24
research is ongoing into newer targeted immune therapies for MS, including
weeks, despite being chemically identical,
the monoclonal antibodies daclizumab, alemtuzumab and ocrelizumab, and
according to data from the EvIDENCE trial.
the T-cell vaccine Tovaxin. However, it is the success in trials of the oral MS
These data allowed the drug to gain FDA
therapies which has created the greatest excitement among investors, and it
approval, despite Avonex holding Orphan
is these which are the most anticipated new treatment options.
Drug exclusivity.
Merck Serono’s cladribine (Mylinax) and Novartis’s fingolimod (FTy-
720), both in regulatory filing, and sanofi-aventis’s teriflunomide, Biogen
Idec’s BG-12, and Active Biotech’s laquinimod, all currently in phase III
development, are the most keenly watched oral pipeline products. These
are at the most advanced stages of development, and have demonstrated
induction of remyelination, reduction in lesions and relapses, and reduced
side effects.
Between the two most advanced drugs, Novartis has edged ahead of Merck
Serono in the race to get the first oral MS treatment to market, having now
filed for approval of fingolimod in the US and Europe. The FDA will conduct
a priority six-month review, which could bring it to market by year-end.
Merck Serono filed its US application for cladribine first, in September
2009, but the FDA rejected the filing two months later as incomplete, which
means that although the filing was resubmitted in june 2010, Novartis will
most likely be the first company to get an oral therapy registered in the US
with fingolimod.

FINGOLIMOd: STRONG EFFICACY BUT CONCERNING
SIdE EFFECTS
Novartis filed fingolimod for approval at the lowest dose studied in trials
(0.5 mg), which had the best benefit-risk profile. Data published from two
late-stage trials have showed fingolimod is effective in reducing relapses,
disability progression and lesions. In the one-year TRANSFORMS study,
involving 1292 patients, the lower dose of fingolimod reduced relapses by
more than 50% compared with Avonex. Robust efficacy was also confirmed
by the FREEDOMS study, in which fingolimod (1.25 mg) reduced the relapse
rate by 60% compared with placebo.
However, questions about the tolerability of fingolimod persist. While efficacy
appeared impressive in TRANSFORMS, the trial highlighted a potentially
concerning side-effect profile. There were two fatal herpes infections, and one
death from a progressive neurological condition of unclear etiology. While the
lower dose appeared to be associated with less risk of infection, opportunistic
infections were still observed in this relatively short-term study. Almost as
concerning was that eight patients on fingolimod (six on the low dose, two
on the high dose) developed melanoma and two developed breast cancer.
Transient reductions in heart rate, increases in blood pressure (1 to 3 mmHg),
elevations in liver enzymes, and increased rates of macular edema were also
seen in fingolimod-treated patients.
As long as these side effects do not worsen with time, it is anticipated
that physicians and patients may be willing to accept the risks, given the
significant demand for oral dosing, and sales are forecast to ramp quickly
upon launch, reaching $853.7 million in 2013. Nonetheless, the threat to
the existing major players in the franchise may be somewhat tempered by
the need for a stringent risk evaluation and mitigation strategies (REMS)
program involving a broad group of specialty physicians.


MYLINAx – PROLONGEd LYMPHOPENIA
MAY BE AN ISSUE
Oral cladribine (Mylinax) is a new formulation of the intravenous
chemotherapeutic cladribine, currently approved for the treatment of hairy Tysabri displays very low rates of relapse with
cell leukemia. Positive data from the phase III CLARITy trial showed a 58% radiographic progression in the real-world setting.
reduction in relapse rate over two years with Mylinax treatment, which while
not as great as the reductions seen with Tysabri, place it above the first-line
interferons. However, the reduction in disability associated with Mylinax
(33%) in CLARITy did not quite match reductions seen with Avonex (37%)
and Tysabri (42%+), although reductions in lesion activity were evident.
As with fingolimod, the biggest question at this stage is cladribine’s safety
profile and its potential to cause elevated incidences of infection. The drug
works by causing moderate-to-severe prolonged lymphopenia, the longer-
term consequences of which are unclear. In addition, CLARITy featured
four cases of cancer and one death from tuberculosis possibly related to the
drug. There may also be some question over whether the drug is suitable for
use in women of childbearing age.
On the positive side, cladribine is viewed as easy to use (as few as 10 days
dosing per year), relatively well tolerated, and strongly efficacious. Should
the clinical sequelae associated with lymphopenia be manageable, oral
cladribine could become a first-line drug with strong clinical potential; sales
are forecast to reach $358.7million in 2013.

REPORTED AND CONSENSUS FORECAST REvENUE (MILLION US$)

Mylinax Fingolimod

900
800
700
600
SALES IN US $

500
400
300
200
100
0 2008 2009 2010 2011 2012 2013 YEAR*

REPORTED SALES

* Data is derived from Thomson Pharma Partnering Forecast


FURTHER ALONG THE ORAL PIPELINE
Sanofi-aventis’s teriflunomide is a pyrimidine synthesis inhibitor with
Fingolimod’s oral convenience may be
immunomodulatory properties. Development has been protracted, with the
offset by demands for multidisciplinary
initial phase III trials beginning in September 2004, first as a monotherapy
monitoring, including liver, dermatology and
and then in combination with interferon. Phase II data have been positive,
infection screening.
with reductions seen in MRI lesions, and a trend towards reduced disability/
number of relapses. However, some degree of immunosuppression was
seen in 49% of patients. The first phase III data, from the TEMSO study, are
expected in 4Q10.
Biogen Idec’s oral second-generation fumarate derivative BG-12 has
completed a 257-patient European phase II dose-ranging trial; data showed
that the drug reduced brain lesion activity at six months versus placebo;
the highest dose (720 mg) reduced the mean number of lesions by 69%
between weeks 12 and 24 and led to a 48% reduction in newly enlarging
T2-hyperintense lesions. There was a trend toward reduction in relapse
rate (32% reduction versus placebo), although this was not significant.
While liver enzyme elevations were observed in 2 to 8% of patients, no
opportunistic infections occurred in patients on BG-12. Two phase III studies,
DEFINE and CONFIRM, have completed enrollment.
Teva’s laquinimod has received fast-track status from the FDA, and the
company believes it could enter the market as soon as late 2011. However,
so far, phase II data have suggested only modest efficacy. Two phase III trials
have completed enrollment. Looking to earlier-stage drugs, Tysabri has
validated blockade of the alpha4-β 1 integrins as a therapeutic approach for
the treatment of MS, and a number of alpha4 integrins are now progressing
through trials, including GlaxoSmithkline’s firategrast (licensed from
Tanabe in December 2000); a Biogen Idec molecule (CDP-323), part of a
collaborative global deal with UCB signed in October 2006, with the same
mechanism of action was discontinued in 2009 due to lack of efficacy.

AdJUNCTIvE THERAPY
Effective oral disease-modifying agents for MS will address the treatment
goal of preventing long-term disability, and their arrival will herald a sea
change in treatment of the disease. However, the scope for oral treatment
has not stopped there, and effective symptom management for MS may
mark another radical change in the dynamics of the market. The first of
these treatment options, Acorda Therapeutics’ sustained-release fampridine
(Ampyra), was approved in january 2010 to improve walking ability in
patients with MS; launch took place in March 2010.
Ampyra successfully completed two SPA-supported phase III trials, which
included patients with primary-progressive, secondary-progressive,
relapsing-remitting and progressive-relapsing disease. The first study
yielded results in 2006; data were strong, and Ampyra met all three
predefined efficacy hurdles. Compared to placebo, a greater proportion of
patients on Ampyra showed a consistent improvement in walking speed
and were classified as responders, the study’s primary outcome (34.8%
versus 8.3%). This effect was maintained throughout the 14-week treatment
period, and there was a significant improvement in the 12-Item MS Walking
Scale for responders versus non-responders. In june 2008, Acorda reported
positive data from a further phase III trial, in which Ampyra demonstrated
a consistent increase in walking speed across all types of MS. The trial’s
primary endpoint was met convincingly, with 42.9% of Ampyra patients
responding to therapy versus 9.3% on placebo. The average increase in
walking speed over the 8 weeks of treatment compared to baseline was
24.7% for the responders compared to 7.7% for placebo.


However, despite favorable efficacy data, prescriptions may be limited
by price concerns, given that the drug is likely to be prescribed alongside
the high-cost disease-modifying agents. Additionally, a dose-related
risk of seizures was observed in trials, which could further temper sales.
Ampyra addresses an important need in terms of reducing symptoms and
consequently the drug is expected to reach sales of $639.6 million in 2013.

SECTION II
dEALS HIGHLIGHTS
The impact of the economic downturn has dramatically influenced the focus
and needs of pharmaceutical companies in recent months. As the financial
markets show early signs of a slow recovery, licensing activity between
companies has been unpredictable but still prevalent and in some cases,
profitable. It is clear that the emphasis on ensuring a signed deal sustains
longevity is rooted at the relationship between companies. The increased
attendance at annual partnering conferences has been a well-observed trend.
Thus, confirming that business development representatives understand the
need to identify potential partners with expertise and knowledge within a
niche field and/or territory, in order to achieve the ideal partnering model of
sustainable agreements and pioneer novel therapeutics.
The major companies in the MS market that have emerged as prominent
deal-making figures include Biogen Idec, Merck Serono and Teva
Pharmaceutical. It is important to note that the concurrent licensing activity
conducted by these parties also emphasizes the competitive need to
maintain partnered agreements.

BIOGEN IdEC: A FAvOREd PARTNER FOR MULTIPLE
SCLEROSIS THERAPEUTICS
Biogen Idec became the exclusive non-US partner for the development of
“We believe that Biogen Idec’s international
Acorda Therapeutics’ Ampyra in july 2009 (see Table 1). This late-stage deal
exemplifies a company realizing the commercialization capabilities of an expertise in MS and neurology also will help
established major player in the worldwide MS therapy market. While the drug us optimize future development of Ampyra
is not expected to achieve blockbuster status, its significant potential was and maximize its value in markets outside
realized by Biogen. As such, the parties agreed to a cost-sharing arrangement, the US.“
with Biogen committing a large upfront payment of $110 million, regulatory
ron Cohen, mD, president and Ceo of acorda
and sales-based milestone payments of up to $400 million and double-digit
royalties on ex-US sales to Acorda. By December 2009, Biogen expected to
receive an additional payment of $45 million in expenses.
Incidentally, Acorda will grant a proportion (7%) of those payments to
the drug’s originator, Elan. This was significant, considering that during
3Q09, Elan and Biogen were locked in a separate legal dispute regarding
blockbuster drug Tysabri.
Elan and Biogen had been collaborating on the program (originally
developed by Elan) since August 2000, as part of a deal worth over $125
million (see Table 1). However, Biogen claimed Elan had breached contract
by signing a Strategic Financing and Collaboration Agreement related
to the drug with a johnson & johnson (j&j) affiliate. In September 2009,
the United States District Court for the Southern District of New york
ruled in favor of Biogen’s claim and Elan terminated the relevant portion
of its transaction with j&j. Despite this unintentional breach, it was clear
that the market clout of Biogen proved to be too valuable an asset to
lose. The companies continue to collaborate under a cost/profit-sharing
arrangement, with no additional milestone payments required; for the
year ending December 31, 2009, $215.9 million was reflected in the two
collaborators’ recorded profit-sharing line for Tysabri.


Biogen demonstrated its aptitude in the MS arena after acquiring BG-12
(dimethyl fumarate) from Swiss firm Fumapharm in October 2003 (see
Table 1); the company was acquired by Biogen in july 2006. The drug was
originally developed for the potential treatment of psoriasis, reaching
phase III of development. However, the partners had agreed to withdraw a
marketing authorization application for psoriasis in Germany by September
2007. Given the strength of BG-12’s anti-autoimmune activity, Biogen
continued to pursue the program for MS and rheumatoid arthritis (RA).
Enrollment of a phase III trial involving 1237 patients was completed in
March 2009.

PARTNER DEAL DEAL vALUE
DRUG COMPANy START DATE (US $)*
fampridine Acorda july 2009 510 million
(Ampyra) Therapeutics (plus royalties)
natalizumab Elan August 2000 125 million
(Tysabri) (plus royalties)
dimethyl Fumapharm October 2003 Undisclosed
fumarate (BG-12)
Table 1: SUMMARy OF BIOGEN IDEC’S MS-RELATED DEvELOPMENT AND
COMMERCIALIZATION AGREEMENTS
* Approximate values based on the achievement of all milestones for the principal components
included in the deal.

BIOGEN FINdS MARkETING PARTNERS FOR AvONEx
Biogen has a widely recognized marketing and distribution network for
its recombinant interferon β-1a –based program Avonex, including Latin
American, Australian, Indian and Nepal, Spain and Nordic regions. The
drug, originally formulated using Inhance drug delivery technology licensed
from Nektar Therapeutics, is marketed by Abbott Laboratories in Latin
American countries, CSL in Australia, Piramal Healthcare in India and
Nepal, and distributed by AstraZeneca in Nordic regions and Schering-
Plough in Spain (see Table 2).

TERRITORIES
PARTNER COMPANy DEAL START DATE COvERED
Abbott Laboratories February 1998 Latin America
CSL june 1999 Australia
Piramal Healthcare December 2003 India and Nepal
AstraZeneca August 1996 Nordic region
(distribution only)
Schering-Plough August 1996 Spain
(distribution only)
Table 2: SUMMARy OF BIOGEN IDEC’S MARkETING AND DISTRIBUTION
DEALS FOR AvONEx

MERCk SERONO dEvELOPS COMPETITOR PROdUCT
TO AvONEx
Merck kGaA’s subsidiary Merck Serono has developed Rebif, another
recombinant interferon β-1a, which was launched in the US in March 2002
after demonstrating superiority to Avonex. Both were designated Orphan
Drug Status for fast-track approval. However, at the time, the FDA informed
Biogen that the drug’s approval letter specifically prohibited labeling with
broad claims of clinical superiority. Merck Serono originally licensed rights to
the drug from the Weizmann Institute of Science (see Table 3).
Following its US launch, Merck Serono enlisted the commercial weight of
pharma giant Pfizer to copromote Rebif. The drug is also comarketed in Italy with
Italfarmaco, under an agreement signed in 1992 with Ares-Serono (see Table 3).


MERCk SERONO ANd TEvA JOIN FORCES AGAINST
MULTIPLE SCLEROSIS
Merck Serono is also developing Mylinax (oral cladribine), licensed on
a worldwide basis from IvAx in October 2002 (see Table 3). Following
Teva’s acquisition of IvAx in january 2006, Teva decided to discontinue its
developmental involvement but continue to offer financial support to the
Merck Serono-led program.
IvAx exclusively licensed oral and intravenous formulations of the drug
from Scripps Research Institute in December 2000, following Scripps’
demonstration of the candidate’s ability to eliminate brain lesions normally
associated with MS observed from patient magnetic resonance imaging
(MRI) scans.

DEAL DEAL
PARTNER TyPE START vALUE
DRUG COMPANy OF DEAL DATE (US $)*
Recombinant Weizmann Development/ By Undisclosed
interferon Institute of commercialization December
β-1a (Rebif) Science worldwide 1992
Recombinant Pfizer Copromotion july 2002 Undisclosed
interferon in the US
β-1a (Rebif)
Recombinant Italfarmaco Comarketing By Undisclosed
interferon in Italy December
β-1a (Rebif) 1992
cladribine Teva Development/ October Undisclosed
(oral; Pharmaceutical commercialization 2002 milestone
Mylinax) worldwide and royalty
payments
Table 3: SUMMARy OF MERCk SERONO’S MAjOR MS-RELATED AGREEMENTS

TEvA’S MAJOR MULTIPLE SCLEROSIS dEALS “After working with Teva since 2004 on
developing laquinimod we believe that Teva
Teva’s non-interferon-based MS therapy Copaxone has been launched in the is the optimal marketing and distribution
US since 1997. The active compound was discovered at the Weizmann Institute
of Science and subsequently licensed to Teva for commercial development.
partner in our territory.“
tomas Leanderson, president & Ceo, active Biotech
While Teva retained the majority of MS development rights, the company
was comarketing the drug in the US with Marion Merrell Dow (MMD),
through the joint venture Teva Marion Partners. In December 1995, Teva
outlicensed worldwide (excluding the US) marketing rights to French
conglomerate sanofi-aventis. Teva acquired sanofi-aventis’ stake in the
joint venture in February 2001; sanofi-aventis continued to receive revenues
from North American sales until March 2008, when Teva reacquired North
American distribution rights.
Currently, Teva and sanofi-aventis continue to jointly commercialize the
drug in major European markets. The two parties copromote the drug in
Germany, Uk, France, Spain, Netherlands and Belgium. sanofi-aventis has
sole marketing rights in other European markets, as well as Australia and
New Zealand (see Table 4).
It was reported that Teva is in the process of reacquiring rights to all
territories by the first quarter of 2012, effectively terminating the agreement;
sanofi-aventis would be eligible to receive predetermined termination
payments in the meantime.
Finally, one of Teva’s most lucrative licensing agreements in the MS arena
stems from its june 2004 deal with Swedish firm Active Biotech for its
phase III autoimmune suppressant laquinimod. The original deal, in which


Active Biotech could earn up to $97 million in upfront and milestone
payments plus royalties, granted Teva exclusive rights to develop, register
and commercialize the candidate worldwide (excluding Nordic and Baltic
regions). These terms were amended in February of this year, granting Teva
Nordic and Baltic territory rights. Active Biotech agreed to receive a higher
royalty rate on eventual sales of the drug (see Table 4).

DEAL
PARTNER TyPE DEAL vALUE
DRUG COMPANy OF DEAL START DATE (US $)*
glatiramer sanofi- Comarketing january 1996 Undisclosed
acetate aventis in Europe
(Copaxone)
Marketing in
Australia/
New Zealand
laquinimod Active Development/ june 2004 97 million
(SAIk-MS) Biotech commercialization (plus
worldwide royalties)
Table 4: SUMMARy OF TEvA PHARMACEUTICAL’S MAjOR MS-RELATED AGREEMENTS

SUMMARY
While the ultimate goal of neuroprotection and repair of damaged areas
of the nervous system remains distant, the addition of new agents to an
interferon or Copaxone backbone may enhance efficacy. However, the
true blockbuster potential lies with a safe and effective oral agent, which
will constitute a new platform therapy. The avoidance of injections and
potentially greater tolerability may also lead to significant increases in
the number of patients with MS who begin and remain on treatment, thus
expanding the market.
So far, licensing activity surrounding MS therapeutics with promising
scientific backing has borne several deals individually worth more than
$100 million, and the future also appears solid. At the R&D end of the
spectrum, novel animal disease models are being evaluated and companies
are collaborating on the development of several promising next-generation
candidates: Merck Serono is investigating orally active tetracycline
derivatives, as part of a development deal with Paratek, and Teva has
partnered with vaccinex on the development of the human monoclonal
antibody vx-15, which Teva is investigating for MS. Lastly, using Dyax’s
proprietary phage display technology, a demyelinating disease program
targeting the Nogo-66 receptor/p75 signaling complex was discovered from
a long-standing collaboration between Biogen and Dyax.
The strategic partnering activity in the market also indicates that not all
pharma companies are collaborating with the well-known major players.
Instead, some firms are actively seeking partners with specific experience
and an established commercial strength. The prospect of potentially novel
oral MS therapeutics also heightens the necessity to utilize companies’
specific formulation expertise.
These first oral therapies are likely to be offered in the very near future,
although physicians will begin to use these without long-term plans for
their use, and careful monitoring of the longer-term effects of more effective
immunomodulation will be required. However, in a decade from now, there
could be ten or more oral therapeutic options for MS, and the revolution in
the treatment of this enigmatic disease may be complete.


NOTES


Image CopyrIght: REUTERS/Enrique Marcarian

THOMSON PHARMA
WORLd LEAdING PHARMACEUTICAL
COMPETITOR INTELLIGENCE SOLUTION

Thomson Pharma® gives you the freedom to explore the
best pharmaceutical content from the extensive collection
of intellectual property, scientific, healthcare and financial
information databases offered by Thomson Reuters. This critical
market intelligence is enhanced and placed in context with unique
abstracts, summaries, commentaries and analysis prepared by
our team of industry experts. No other data source puts so much
information at your fingertips.

For more information visit
go.thomsonreuters.com/thomsonpharma

AWARDED TO THOMSON SCIENTIFIC LIMITED
(THE SCIENTIFIC BUSINESS OF THOMSON REUTERS)

Image CopyrIght: iSTOCkPHOTO

THOMSON PHARMA
PARTNERING FORECAST
CREdIBLE dATA FOR CREATING
QUALITY SALES FORECASTS
Thomson Pharma® Partnering Forecast offers both market-based
consensus analyst forecasts and transparent patient-based
forecasts along with drug summaries from Thomson Pharma’s
trusted pipeline database. Review and adjust with your own
assumptions to quickly generate your own forecasts.

For more information visit go.thomsonreuters.com/forecast

©2010 Thomson Reuters. All rights reserved. Thomson Reuters and the kinesis logo are trademarks of Thomson Reuters.

To sign up to our Pharma Matters range of publications visit:
go.thomsonreuters.com/pharmamatters

THE ONES TO WATCH
Focuses on the latest phase changes in the pharmaceutical pipeline.
SPOTLIGHT ON
Snapshot of the current market players and deals being done in a certain therapy area.
MOvERS ANd SHAkERS
Unravels the most significant game-play in the US generics market.
THE CUTTING EdGE OF CHEMISTRY
Insights into the chemistry advances transforming drug discovery and development.

ABOUT THOMSON PHARMA
Thomson Pharma brings together the best pharmaceutical data owned by
Thomson Reuters in a single comprehensive solution containing millions of pieces
of information. And it’s not just data. Thomson Pharma extends and deepens its
knowledge with unique abstracts, commentaries and analysis prepared by our team
of industry experts. You can link at a click between different types of content. No other
data source puts so much information at your fingertips.
In place of your legacy indexing systems, multiple interfaces, and complex data
sources, imagine how Thomson Pharma can simplify your information needs, justify
and speed your decision-making, and keep you abreast of the market.
ABOUT THOMSON PHARMA PARTNERING FORECAST
Thomson Pharma Partnering Forecast gives you the most accurate available method of
assessing the sales potential of new drugs by integrating and summarizing multiple
perspectives on drugs that will compete with yours.
For each therapeutic franchise, Thomson Pharma Partnering Forecast enables you to
compare the most significant candidates in the development pipeline and the key
drugs that have reached the market. It provides a consensus of analyst forecasts for
pipeline and marketed drugs, and downloadable, patient-based revenue models for
drugs in more than 100 indications, providing transparent assumptions on incidence
and prevalence, eligible numbers of patients, estimated timing of approval, pricing,
and market share within the indication.
In addition to proprietary revenue forecasts, catalysts and likelihood of approvals are
provided through a partnership with BioMedTracker.
ABOUT THOMSON REUTERS
Thomson Reuters is the leading source of intelligent information for professionals
around the world. Our customers are knowledge workers in key sectors of the global
economy. We supply them with the intelligent information they need to succeed in
fields that are vital to developed and emerging economies such as law, financial
services, tax and accounting, healthcare, science and media.
Our knowledge and information is essential for drug companies to discover new drugs
and get them to market faster, for researchers to find relevant papers and know what’s
newly published in their subject, and for businesses to optimize their intellectual
property and find competitive intelligence.

NOTE TO PRESS:
heaLthCare & SCIenCe To request further information or permission to reproduce content from this report,
regIonaL offICeS please contact:
North america
Philadelphia +1 800 336 4474
Paul Sandell
+1 215 386 0100 Phone: + 44 20 7433 4704
Email: paul.sandell@thomsonreuters.com
latin america
Brazil +55 11 8370 9845 For more information on Thomson Pharma and Thomson Pharma Partnering Forecast
Other countries +1 215 823 5674
visit: go.thomsonreuters.com/commercial or email
europe, Middle east and africa scientific.lifesciences@thomsonreuters.com
London +44 20 7433 4000

asia Pacific
Singapore +65 6775 5088
Tokyo +81 3 5218 6500

For a complete office list visit:
science.thomsonreuters.com/contact

ph1008257

Copyright © 2010 Thomson Reuters

Spotlight On... Multiple Sclerosis, Sep. 2010 -- Pharma Matters Report

Recommandé

Recommandé

Contenu connexe

En vedette

En vedette (11)

Plus de Thomson Reuters

Plus de Thomson Reuters (14)

Dernier

Dernier (20)

Spotlight On... Multiple Sclerosis, Sep. 2010 -- Pharma Matters Report