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Lemtrada Approved!

As reported by Reuters below. Presented without comment.

FDA panel supports approval of Sanofi MS drug Lemtrada

BY DEBORAH ZABARENKO

SILVER SPRING Wed Nov 13, 2013 10:19pm GMT

(Reuters) – A federal advisory panel recommended approval of Sanofi SA’s experimental multiple sclerosis drug Lemtrada on Wednesday, but said the drug should be reserved for patients who have failed other therapies.

In a surprise decision, an advisory panel to the Food and Drug Administration voted 14 to 0, with one abstention, that the drug should be approved despite its potential to cause cancer and other serious conditions.

“Do I want to take this drug? No way!” said Dr. Nathan Fountain of the University of Virginia School of Medicine and the panel’s

chairperson. But for some patients, he said, it could be appropriate. “I wouldn’t want to deny those people,” he said.

The panel’s recommendation follows an initial report last week by reviewers for the FDA, who raised grave concerns about the drug’s potential to cause an array of autoimmune conditions, in which the body mistakenly attacks its own cells, as well as its potential to cause thyroid, skin and breast cancer.

The reviewers also questioned whether the way clinical trials of Lemtrada were conducted had biased the results in favor of the drug.

Advisory panelists, who met in Silver Spring, Maryland, said the risks could be worth it for some difficult-to-treat patients.

“The risks are very substantial, but this is a really bad disease,” said Dr. Paul Rosenberg of Johns Hopkins University School of Medicine.

Multiple sclerosis is a chronic, autoimmune disease that affects more than 2.5 million people worldwide and up to 500,000 in the United States, according to the Multiple Sclerosis Foundation. It can cause muscle weakness, pain, and speech and cognitive difficulties.

Lemtrada, which was approved in Europe in September, was at the heart of Sanofi’s lengthy, $20.1 billion takeover battle for Genzyme Corp., which developed the drug. Sanofi finally acquired Genzyme in 2011.

As part of the takeover deal, Genzyme shareholders received contingent value rights, known as CVRs, entitling them to future payments of up to $14 a share if certain goals were met, including approval for Lemtrada.

The price of the CVRs has fallen 67 percent to 66 cents since the FDA posted its review last week.

If Lemtrada, also known as alemtuzumab, is approved, it is expected to generate peak sales of $752 million by 2018, according to seven analysts polled by Thomson Reuters.

The FDA is not bound to follow the advice of its advisory committees but typically does so.

(Reporting by Deborah Zabarenko, writing by Toni Clarke; Editing by Leslie Adler)

 
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Posted by on November 14, 2013 in News, Portfolio, US Market

 

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GCVRZ: Lemtrada FDA approval imminent

Disclamer: The author has a position in the Genzyme Contingent Value Rights (GCVRZ).

A few days ago, Lemtrada was approved by the regulatory authorities in Europe for the European market.

Regulatory agencies like the FDA are a little like the rating agencies in the financial world in that their decisions often mirror each other. Therefore, with this approval, I believe that the FDA approval of Lemtrada is now imminent.

Generally, I have found that European regulatory authorities are faster and more willing to take a risk with a new drug. So this is the case with Lemtrada which is approved first in Europe. With the approval of Lemtrada in Europe, this paves the way for FDA to approve it in the US as well.

Once FDA approves the drug, the second milestone payment of $1 will be triggered for the holders of GCVRZ.

I reproduce below the press release from Sanofi and the recommendations of the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) which gave rise to the approval.

European Commission Approves Genzyme’s Multiple Sclerosis Treatment Lemtrada™ (alemtuzumab)

  • Follows Recent European Commission Approval of Multiple Sclerosis Treatment Aubagio® (teriflunomide)
  • Approvals Set the Stage for Launches Throughout EU and Strongly Position Genzyme as a Committed Partner to the MS Community

Sanofi-Genzyme-logoParis, France – September 17, 2013 – Sanofi (EURONEXT: SAN and NYSE: SNY) and its subsidiary Genzyme announced today that the European Commission has granted marketing authorization for Lemtrada™. This follows the August 30th approval of Aubagio®. The company intends to begin launching both products in the EU soon.

“The approvals of Lemtrada and Aubagio in the European Union represent an important milestone for Genzyme and demonstrate our focus on scientific innovation and commitment to multiple sclerosis patients,” said Genzyme CEO and President, David Meeker, M.D. “This is particularly exciting as the EU approval is the first for Lemtrada globally. We look forward to making these unique therapies available to MS patients very soon.”

Lemtrada is indicated for the treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features. Lemtrada 12 mg has a novel dosing and administration schedule of two annual treatment courses. The first treatment course of Lemtrada is administered via intravenous infusion on five consecutive days, and the second course is administered on three consecutive days, 12 months later.

The Lemtrada clinical development program included two pivotal randomized Phase III studies comparing treatment with Lemtrada to high-dose subcutaneous interferon beta-1a (Rebif®) in patients with RRMS who had active disease and were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II), as well as an ongoing extension study. In CARE-MS I, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates; the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a.

The most common side effects of Lemtrada are infusion associated reactions, infections (upper respiratory tract and urinary tract), lymphopenia and leukopenia. Serious autoimmune conditions can occur in patients receiving Lemtrada. A comprehensive risk management program will support early detection and management of these autoimmune events.

Aubagio 14 mg is a once-daily, oral therapy indicated for treatment of adult patients with RRMS. The EU approval was based on data from the Phase III TEMSO (TEriflunomide Multiple Sclerosis Oral) and TOWER (Teriflunomide Oral in people With relapsing remitting multiplE scleRosis) trials. The EU approval of Aubagio includes new active substance designation.

“Multiple sclerosis necessitates a highly individualized treatment approach, and the increasing diversity of options is good news,” said Hans-Peter Hartung M.D., Ph.D., Professor and Chairman of the Department of Neurology at Heinrich-Heine-University in Duesseldorf, Germany. “The Lemtrada clinical trial data support its potential to meaningfully address disability in active RRMS patients, while Aubagio’s efficacy, safety and convenient dosing may provide an important alternative to injectable therapies. The approvals of Lemtrada and Aubagio represent a significant step forward in the way we think about treating this disease.”

Multiple sclerosis is estimated to affect more than 2.1 million people globally. There are approximately 630,000 people affected by MS in Europe.

“This is a hopeful time for people with MS,” said John Golding, President of the European Multiple Sclerosis Platform. “These approvals demonstrate the great progress being made towards introducing more differentiated treatment options that address important unmet needs.”

FDA action on Genzyme’s supplemental Biologics License Application seeking U.S. approval of LemtradaTM (alemtuzumab) for the treatment of relapsing MS is expected in late 2013. Lemtrada is also under review by other regulatory agencies. Aubagio is approved to treat relapsing MS in the United States, Australia, Argentina, Chile, and South Korea, and is under review by additional regulatory agencies.

LEMTRADA has been in active clinical development for MS for more than 10 years. The clinical development program involved more than 1,700 patients.

EMANew

Summary of Opinion

27 June 2013
EMA/377379/2013
Committee for Medicinal Products for Human Use (CHMP)

On 27 June 2013, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Lemtrada 12 mg alemtuzumab in 1.2 ml (10 mg/ml) concentrate for solution for infusion intended for the treatment of relapsing remitting multiple sclerosis. The applicant for this medicinal product is Genzyme Therapeutics Ltd. They may request a re-examination of any CHMP opinion, provided they notify the European Medicines Agency in writing of their intention within 15 days of receipt of the opinion.

The approved indication is: “treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features “.

Alemtuzumab is a humanized monoclonal antibody directed against the cell surface glycoprotein CD52. The mechanism by which alemtuzumab exerts its therapeutic effects in multiple sclerosis is not fully elucidated. However, research suggests immunomodulatory effects through depletion and repopulation of lymphocytes.

The benefits with Lemtrada are its ability to reduce the relapse rate and slow disability progression.

The most common side effects are infusion associated reactions (including headache, flushing, nausea, urticaria, rash, pruritus, pyrexia and fatigue), upper respiratory tract infection, urinary tract infection, lymphopenia and leukopenia. In addition, side effects pertaining to the thyroid gland (including overactive or under-active thyroid gland, or goitre and auto-immune conditions) were commonly observed in patients treated with alemtuzumab.

A pharmacovigilance plan for Lemtrada will be implemented as part of the marketing authorisation.

Treatment with Lemtrada should be initiated and supervised by a neurologist experienced in the treatment of patients with MS. Specialists and equipment required for the timely diagnosis and management of the most frequent adverse reactions, especially autoimmune conditions and infections, should be available.

Resources for the management of hypersensitivity and/or anaphylactic reactions should be available.

Patients treated with Lemtrada must be given the Patient Alert Card and Patient Guide and be informed about the risks of Lemtrada.

Detailed recommendations for the use of this product will be described in the summary of product characteristics (SmPC), which will be published in the European public assessment report (EPAR) and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.

The CHMP, on the basis of quality, safety and efficacy data submitted, considers there to be a favourable benefit-to-risk balance for Lemtrada and therefore recommends the granting of the marketing authorisation.

 
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Posted by on September 20, 2013 in News, Portfolio, US Market

 

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GCVRZ: Lemtrada Nearing Approval

Disclosure: We have a position in GCVRZ which was established at a price slightly below the current market price.

Sanofi MS drug nears green light after pass-the-parcel marathon

By Ben Hirschler

LONDON, June 10 (Reuters) – One of the world’s longest running drug development sagas may draw to a close this month as French firm Sanofi hopes for a European green light for its new multiple sclerosis medicine Lemtrada.

The drug’s quarter-century journey from a laboratory in Cambridge, England, to a possible $1 billion-a-year seller has involved a string of pass-the-parcel deals that serve as an object lesson in complex “drug dealing” between rival companies.

While Sanofi may end up with a new product to plug a hole in its medicine cabinet, the drug’s slow evolution is a mixed blessing in the eyes of some doctors worried about pricing.

But for the original scientists behind the antibody treatment, it has been a frustrating wait.

“It’s been painful,” said Herman Waldmann, emeritus professor of pathology at the University of Oxford, who co-invented the drug while at the University of Cambridge.

“We had to make the running to keep on convincing the pharmaceutical industry at every step that there was something interesting there.”

After studying Lemtrada, also known as alemtuzumab, in multiple sclerosis (MS) since the early 1990s, he believes the drug’s infrequent infusions have a lot to offer patients.

Sanofi, too, is optimistic about a medicine that would mark its second victory in MS, following last year’s U.S. approval of Aubagio, a pill. It expects an EMA verdict by mid-year, implying a decision at the agency’s next expert meeting on June 24-27.

EMA decisions are usually endorsed by the European Commission within a couple of months.

Over the years, enthusiasm for Lemtrada, which works by knocking out immune system cells called lymphocytes, has ebbed and flowed and there is still no guarantee it will be approved.

Wellcome, now GlaxoSmithKline, took an early stab at developing the medicine in the 1990s – after acquiring rights via British Technology Group – but gave up.

The drug went back on the market, passing through the hands of U.S. biotech firms Leukosite and then Ilex Oncology, which struck a partnership deal with Schering, now Bayer, in 1999.

In 2001, it was approved as a treatment for B-cell chronic lymphocytic leukaemia (B-CLL) and marketed under the brand name Campath – a reference to the department of pathology in Cambridge where it was created. Sales, however, never took off.

It changed hands again after U.S.-based Genzyme bought Ilex in 2004 – paving the way for a final ownership switch in 2011, when Sanofi bought Genzyme for $20.1 billion.

Crowded Market

Lemtrada’s prospects were at centre-stage in that drawn-out takeover battle, leading to an eventual deal that included listed contingent value rights linked to Lemtrada’s future success.

Handicapped partly by its late arrival, analysts predict the drug will not be the first choice in a market where competition has exploded with the launch of Novartis’s Gilenya and Biogen Idec’s Tecfidera, both pills.

“In Europe, there’s little doubt it will be kept for fairly advanced stages of MS and I would expect it to be positioned similar to (Biogen’s) Tysabri,” said Eric Le Berrigaud, an analyst at Bryan Garnier & Co in Paris.

A U.S. regulatory decision on its use is still pending.

Like Tysabri, Lemtrada has a potent effect on MS, which is caused by abnormal immune attacks on the protective sheath surrounding nerve cells. But its potency also raises safety issues and the fact it is given through two cycles of infusions, 12 months apart, means any side effects are not easily reversed.

The consensus for annual Lemtrada sales is some $700 million by 2017, according to forecasts compiled by Thomson Reuters Pharma – a number that could rise “by a few hundred million” if the drug gets a European green light, according to Le Berrigaud.

After all the delays, the drug has patent protection until only 2017 in the United States and 2014 in Europe, although Sanofi says it is “actively pursuing” additional patent cover.

Pricing Controversy

The drug’s long history and existing use in leukaemia poses a pricing dilemma for Sanofi, prompting the French firm to take the unusual step last year of pulling Campath off the market to stop its unauthorised use in MS.

It will, however, still be available free of charge to established B-CLL patients through a special access scheme.

The move gives Sanofi freedom to relaunch Lemtrada at higher price, potentially putting it on a par with other new MS drugs that, in the United States, cost $55,000-$60,000 a year.

In terms of protecting shareholders’ interest, it is a smart decision – but some doctors are not impressed. The Lancet medical journal expressed concern in an editorial last year and there is also worry among transplant surgeons who have been using Campath off-label – for other than its designated use – to help prevent rejection after operations.

Roy Calne, a British organ transplantation pioneer, said using Campath slashed the need for costly maintenance drugs and the alternative was 10 times more expensive.

Sanofi CEO Chris Viehbacher, though, needs a decent return from Lemtrada to help offset sales lost as older products face generic competition. He knows the drug better than many: he was working at Wellcome back in the 1990s when the decision was made to discontinue its development.

 
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Posted by on June 11, 2013 in News, Portfolio, US Market

 

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Sanofi’s Lemtrada Contingent Value Rights (GCVRZ)

lemtrada-logo

Nearly all my investments are concentrated in Vietnam.

However, every now and then, I find something interesting in other markets. Recent examples include my foray into selling calls on Wells’ Fargo Bank (NYSE : WFC) and buying the preferred stock of the National Bank of Greece (NYSE : NBG-PA). These have turned out okay (so far) but these are by their nature risky investments so it may not be for everyone.

lemtradaRecently, I came to know about a very unusual security: Contingent Value Rights (CVRs). This is a security which is like a long dated call option/warrant. But unlike other options/warrants which have a payout based on the price of another security, this CVR’s payout is based on the future sales performance of a certain monoclonal antibody called Alemtuzumab or Lemtrada as it is commonly known.

Background

These CVR securities (NASDAQ : GCVRZ) were created when Sanofi bought over Genzyme and former Genzyme shareholders were given these CVRs as part of the buyout.

At that time, Sanofi could not agree with Genzyme what a key drug in Genzyme’s portfolio, Lemtrada, was worth. Sanofi felt that $700 million was a fair estimate of Lemtrada’s market potential but Genzyme felt that a whooping $3.5 billion in sales was the accurate estimate.

This lies the biggest risk of this security. It is very very hard to value.

Even two very knowledgeable pharmaceutical companies cannot agree on Lemtrada’s value; So you can be sure that >99% of people who hold these CVRs have little idea what they are worth.

Payout Table

These CVRs have a payout which is summarized below:

Event Payout Timing
Production target of Cerezyme and Fabrazyme (missed) $1 1H2012
FDA Approval $1 1H2013
Sales over $400mil $2 2014
Sales over $1.8 bil $3 Anytime until 2020
Sales over $2.3 bil $4 Anytime until 2020
Sales over $2.8 bil $3 Anytime until 2020
Total $14

First Milestone Missed

So far, the first milestone target has been missed.

Likely due to manufacturing problems with Cerezyme and Fabrazyme, which were present since 2010 (cerefabrazyme), the company did not meet the first milestone target. The price of the CVRs plunged after this fact was announced on 28 Jul 2011.

Now, investors are counting on the second target.

Approval by FDA

By most accounts, the approval of Lemtrada by FDA is almost certain (>95% probability) and is expected to occur by the second half of 2013.

This approval will trigger the $1 milestone payment to CVR holders.

While I am not certain on Lemtrada’s market potential, I am pretty certain based on current clinical data, FDA will approve the drug so the milestone will be met.

Once this happens, the CVRs will likely trade above the current price of $1.85 per CVR.

Based on reports, Sanofi had just submitted the application to FDA for review last month (fdafiling). I expect FDA to approve this drug without a hitch.

If there is a delay, i.e. by FDA requesting for more information from Sanofi on Lemtrada, the CVRs will likely take a significant hit in the price. This in my view will be an opportunity to buy more. I do not think FDA will be likely to ask for more information from Sanofi but would be happy for them to do so as the ensuring sell off in the CVRs will create an opportunity for me to establish a larger position at an even lower price.

Below are the original papers that establish the efficacy of Lemtrada as a treatment for MS. One should read and decide for onself. To me I feel that this is pretty convincing evidence, sufficient for FDA to approve the drug.

Lancet papers

Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial.

Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial

This short video is a rather helpful explanation on the clinical trials on Lemtrada:

Dutch Tender Offer

What gives me much confidence that the current CVR price is a fair one is because Sanofi organised a tender offer for these rights last year on 4 Sep 2012 (tender_en).

The fact that Sanofi chose to tender about a third of the CVRs gives me confidence that Lemtrada would be a successful drug.

More information on CVRs

CVR_QA_Final : FAQ on Lemtrada CVRs by Sanofi.

presentationcvrs : “Bridging the valuation gap” by Igor Kirman, 8 Sep 2011.

 
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Posted by on February 15, 2013 in Portfolio, US Market

 

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