The U.K.’s health-cost regulator asked Sanofi for more information on its multiple-sclerosis drug Lemtrada, less than a month after U.S. regulatory advisers said the drug’s trials weren’t adequate to assess its efficacy.
The National Institute for Health and Care Excellence is seeking clarifications on the evidence Paris-based Sanofi’s Genzyme unit submitted on the drug, NICE said in draft guidance today. Sanofi has until Jan. 9 to submit the extra information, the institute said. NICE, which advises the U.K.’s National Health Service on which treatments provide value for money, didn’t specify what information it requested.
Lemtrada, approved in the European Union in September, was a key part of Sanofi’s $20 billion acquisition of Genzyme in 2011. The U.S. Food and Drug Administration is expected to decide by the end of this year whether to approve the drug, which will compete in an increasingly crowded market against treatments such as Novartis AG’s Gilenya and Teva Pharmaceutical Industries Ltd’s Copaxone.
Lemtrada may generate sales of 455 million euros ($619 million) in 2017, according to the average of eight analysts’ estimates compiled by Bloomberg. Bayer AG (BAYN) plans to co-promote the drug in the U.S. and will receive payments based on sales. Sanofi said in October it would charge 8,645 euros per vial for the drug in Germany.
Sanofi fell 0.3 percent to 74.71 euros as of 11:39 a.m. in Paris. The stock has gained 8 percent this year, including reinvested dividends, compared with a 25 percent advance in the Bloomberg Europe Pharmaceuticals Index.
The drug is a so-called monoclonal antibody administered to patients through two sets of infusions a year apart. Late-stage clinical trials showed the treatment slowed the progression of disability, though it also led to infections and an autoimmune thyroid-related side effect in some patients.
Sanofi’s first MS therapy, a tablet called Aubagio, won approval in the U.S. last year and in the EU this year. The drugmaker is counting on new products to offset revenue losses from generic competition to best-sellers including the blood-thinner Plavix.
Multiple sclerosis is a debilitating disease that attacks the central nervous system. Relapses, or flare-ups, are episodes of worsening neurological function. More than 100,000 people in the U.K. have the disease, according to the Multiple Sclerosis Trust.
An FDA advisory committee voted last month that Lemtrada is effective for preventing flare-ups of the disease, even as it decided the company’s trials weren’t adequate to assess the drug.
Source: Bloomberg ©2013 BLOOMBERG L.P.(05/12/13)
Lemtrada hasn’t proven to help against disability in the treatment of relapsing multiple sclerosis, said U.S. advisers who questioned whether the company’s studies were conducted well enough to assess the drug.
While the U.S. Food and Drug Administration advisory panel decided that potential safety risks don’t preclude approval of Lemtrada, its members voted 14-2 that the drug didn’t help improve a patient’s disability. The agency isn’t required to accept the recommendations of its advisers.
Lemtrada, approved in the Europe Union in September, was a key part of Paris-based Sanofi’s $20 billion acquisition of Genzyme Corp. in 2011. If cleared in the U.S., the drug would enter a crowded field in which relapsing MS patients now have 10 treatment options with varying degrees of efficacy, including Biogen Idec Inc.’s Tecfidera and Teva Pharmaceutical Industries Ltd.’s Copaxone.
“If the study is biased, then everything that flows from the study can’t be trusted,” Robert Clancy, a panel member and professor of neurology and pediatrics at the University of Pennsylvania School of Medicine, said at yesterday’s meeting. The panel voted 11-6, with one abstention, that the two large studies Sanofi submitted on the drug’s behalf weren’t adequate and well-controlled.
The FDA is expected to decide whether to approve Lemtrada by Dec. 27. The agency will probably issue a so-called complete response letter that rejects the drug until the company does further work, said Jeffrey Holford, an analyst at Jefferies in New York.
“With the panel voting that the studies were not adequate and well-controlled, the FDA probably has to issue a CRL,” Holford wrote in a note today. “We continue to see the probability of approval at 20 percent to 30 percent.”
Lemtrada may generate sales of $672 million in 2017, according to the average of eight analysts’ estimates compiled by Bloomberg. Bayer AG plans to co-promote the drug and will receive payments based on sales.
Multiple sclerosis is a debilitating disease that attacks the central nervous system. Relapses, or flare ups, are episodes of worsening neurological function, according to the National MS Society.
Several patients who said they had severe MS testified today in favour of Lemtrada’s approval, imploring panel members to leave the weighing of risk versus benefit to those who have the disease and their physicians.
“It’s critical that people with significant disease who stand to lose function and become disabled have the opportunity to access this drug,” said David Goldblatt, a neuroradiologist from Austin, Texas, who said he started taking Lemtrada 10 years ago.
“I understand your issues with safety,” Goldblatt told the panel. “I think that nowadays patients are taking more responsibility and should be allowed to make the decision that they may decide that the risk/benefit ratio is adequate for them, that they would like to take this medication.”
The panel agreed, with many members saying they voted that the drug’s safety issues didn’t preclude its approval because patients should be allowed to make that decision with their doctor. While panelists said the drug appeared to be effective against the disease, they also voted unanimously that Lemtrada shouldn’t be a first option for patients, if approved.
“For the foreseeable future, I would rank it as a third-line drug,” said Justin Zivin, a panel member and professor emeritus at the University of California at San Diego.
FDA staff determined in a Nov. 8 report that Sanofi’s annual infusion has “serious and potentially fatal safety issues” including risk of cancer and autoimmune and thyroid diseases. FDA staff also questioned Sanofi’s claims the drug is effective.
The company’s decision not to keep secret which patients in clinical research were taking the medicine or an older treatment and the subjective nature of determining whether the drug was working may have skewed results, agency staff said. That was a main focus of yesterday’s FDA advisory panel discussions.
Sanofi said it was unable to keep that information confidential because of the differences in how the drugs, Lemtrada and an older treatment, were given, including annual dosing compared with three times a week. Follow-up data showed findings consistent with clinical trial results, Sanofi said in an e-mailed statement on Nov. 8.
“We are pleased that the advisory committee clearly recognized the effectiveness of Lemtrada and voted unanimously that the safety profile should not stand in the way of approval,” Jack Cox, a spokesman, said in an e-mailed statement today. “The committee vote did acknowledge FDA’s concerns around study design but this appears not to have had an impact on the committee’s votes of the effectiveness and safety profile of Lemtrada. We will work with the agency to support their completion of the review process.”
Lemtrada won European Union approval in September and the active ingredient alemtuzumab was cleared by the FDA in 2001 to treat a certain form of leukemia, though the drug is no longer for sale.
Other treatments for relapsing MS include another Sanofi drug Aubagio, Biogen’s Tecfidera and Tysabri and Teva’s Copaxone. Lemtrada is given through two courses of infusions given a year apart.
Source: Bloomberg ©2013 BLOOMBERG L.P. (14/11/13)
Sanofi’s multiple sclerosis treatment Lemtrada may not offer enough benefit to patients to outweigh risks including cancer, U.S. regulators said. The French drugmaker’s shares fell.
Lemtrada’s “serious and potentially fatal safety issues,” which include the risk of autoimmune and thyroid diseases, may make the medicine too dangerous to approve unless there is substantial clinical benefit shown, Food and Drug Administration staff said in a report today. Agency reviewers also questioned whether Sanofi conducted adequate trials to prove the annual infusion works.
“That’s like a death sentence,” said Fabian Wenner, an analyst with Kepler Cheuvreux in Zurich, “It isn’t what everyone expected, an issue with the safety. It seems to be a more fundamental issue here.”
Lemtrada, approved in Europe earlier this year, was at the center of Paris-based Sanofi’s $20 billion acquisition of Genzyme Corp. in 2011. Shareholders who have contingent value rights stand to receive cash payments if Lemtrada is approved. Bayer AG (BAYN) plans to co-promote Lemtrada and will receive payments based on sales.
“The certainty of the risks of potentially lifelong hypothyroidism, serious infusion reactions, melanoma and other malignancies, Graves’s ophthalmopathy and other autoimmune disorders, and prolonged increased susceptibility to infection may not be balanced by the uncertainty that exists in the limited evidence of the potential clinical benefits from clinical trials that were not well-controlled,” FDA drug reviewer John Marler wrote in the report.
Nov. 13 Panel
An advisory panel on Nov. 13 will discuss whether to recommend the drug’s approval. The FDA is expected to decide whether to clear the medicine for treating relapsing MS patients by the end of the year.
Sanofi did submit trial evidence that showed Lemtrada had a significant benefit, though the company’s decision to not keep secret which patients were taking the medicine and the subjective nature of determining whether the therapy was working may have skewed results, Marler said.
Sanofi said it was unable to keep that information confidential because of the differences in how the drugs, Lemtrada and an older treatment, were given, including annual dosing compared with three times a week. Follow-up data showed findings consistent with clinical trial results, Sanofi said in an e-mailed statement.
“Our company is confident that Lemtrada offers an important step forward in the way physicians and patients will think about treating multiple sclerosis,” Sanofi said.
Sanofi fell less than 1 percent to 77.94 euros at 4:21 p.m. Paris time. The contingent value rights linked to the Genzyme acquisition dropped 68 percent to 65 cents in New York trading.
Genzyme stockholders had received one right entitling the owner to additional fees of as much as $14 per CVR by the end of 2020 if Sanofi met certain goals, most of them tied to the approval and sale of Lemtrada.
Lemtrada won European Union approval in September and the active ingredient alemtuzumab was cleared by the FDA in 2001 to treat a certain form of leukemia, though it is no longer for sale.
The drug may generate sales of $691 million in 2017, according to the average of eight analysts’ estimates compiled by Bloomberg.
Source: Bloomberg ©2013 BLOOMBERG L.P. (08/11/13)
Latest data from the CARE-MS II extension study show that alemtuzumab (Lemtrada, Genzyme/Sanofi) has a durable effect on disability in multiple sclerosis (MS), with the mean Expanded Disability Status Scale (EDSS) score at 3 years still below that at baseline.
These new data were presented in a poster at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) last week.
Summing up the highlights of the meeting, Bernd Kieseier, MD, Heinrich Heine University, Düsseldorf, Germany, commented on these latest alemtuzumab results: "Of those patients stable at 2 years, almost 50% are stable in the third year without any further treatment and 20% have better disability scores. And of those who improved in the core study 10% improve more in the third year and 42% remain stable."
Dr. Kieseier added: "These data clearly support the view that we have a potent drug here. It has a dramatic effect on EDSS, with some patients actually improving, and this is maintained in third year even without further treatment."
Commenting for Medscape Medical News, Jeffrey Cohen, MD, Cleveland Clinic, Ohio, who was not involved in this analysis, said, "These results tell me that the short-term benefit seen in the trial is maintained after the trial has ended. The drug continues to be beneficial for years after dosing. We have already seen this to be the case in phase 2 trials, where there has been up to 5 years' benefit. So this is no big surprise."
Noting that the mean EDSS score did increase slightly between year 2 and year 3, Dr. Cohen said the change was very small and "the score looks quite stable to me."
The CARE-MS II (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis II) trial http://www.medscape.com/viewarticle/773790 randomly assigned patients with active relapsing/remitting MS to treatment with alemtuzumab or interferon β. Alemtuzumab was given as a 12 g/d intravenous infusion on 5 consecutive days at baseline and 3 consecutive days 1 year later.
More than 90% (393 of 423) of patients who had received alemtuzumab, 12 mg, in CARE-MS II and completed the core study entered the extension. Of these, 20% received a further dose during the third year. Fewer than 3% of patients received another disease-modifying therapy in year 3.
In these patients, mean EDSS score increased slightly from year 2 to year 3 but still remained below the baseline score.
At year 3, 70% of alemtuzumab-treated patients had stable or improved EDSS scores from baseline. Results were similar to those seen at year 2.
In addition, 66% of patients had stable or improved EDSS scores from the start of the extension study (end of year 2).
Among patients whose EDSS scores remained stable from baseline to year 2, 67% continued to remain stable or improved from year 2 to year 3. And among patients whose EDSS score improved from baseline to year 2, 53% remained stably improved or improved further from year 2 to year 3.
At year 3, more than one third of patients who had received alemtuzumab in the core study attained improvement in pre-existing disability that was sustained for 6 months, and more than a quarter achieved improvement in pre-existing disability that was sustained for 12 months.
The CARE-MS trials were funded by Genzyme/sanofi aventis. Dr. Kieseier has received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Bayer Health Care, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, sanofi aventis, and TEVA Pharmaceuticals. Dr. Cohen reports personal compensation for serving as a consultant or speaker from Biogen Idec, Elan, Novartis, Teva, and Vaccinex and research support paid to his institution from Biogen Idec, Consortium of MS Centers, US Department of Defense, Genzyme, National Institutes of Health, National MS Society, Novartis, Receptos, Synthon, and Teva.
29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Poster presentation #P592. Presented October 3, 2013.
Source: Medscape Copyright © 1994-2013 by WebMD LLC (11/10/13)
Genzyme, a Sanofi company announced today that the European Commission has granted marketing authorization for Lemtrada(TM). This follows the August 30th approval of Aubagio(R). 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(R)) 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 2.5 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 Lemtrada(TM) (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.
About Lemtrada(TM) (alemtuzumab)
Alemtuzumab is a monoclonal antibody that selectively targets CD52, a protein abundant on T and B cells. Treatment with alemtuzumab results in the depletion of circulating T and B cells thought to be responsible for the damaging inflammatory process in MS. Alemtuzumab has minimal impact on other immune cells. The acute anti-inflammatory effect of alemtuzumab is immediately followed by the onset of a distinctive pattern of T and B cell repopulation that continues over time, rebalancing the immune system in a way that potentially reduces MS disease activity.
Genzyme holds the worldwide rights to alemtuzumab and has primary responsibility for its development and commercialization in multiple sclerosis. Bayer HealthCare retains an option to co-promote alemtuzumab in multiple sclerosis. Bayer HealthCare has notified Genzyme of its intention to co-promote under this option. Upon regulatory approval and commercialization, Bayer would receive contingent payments based on sales revenue.
Lemtrada(TM) is the proprietary name submitted to health authorities for the company's investigational multiple sclerosis agent alemtuzumab.
EU Indication and Usage
Lemtrada is indicated in the European Union for the treatment of adult patients with relapsing remitting multiple sclerosis with active disease defined by clinical or imaging features.
Important Safety Information About Lemtrada for EU patients
Serious autoimmune conditions such as immune thrombocytopenia (ITP), glomerulonephritis and thyroid disease can occur in patients receiving Lemtrada. ITP and glomerulonephritis occur infrequently. Thyroid adverse events (hyperthyroidism and hypothyroidism) are commonly observed in patients treated with Lemtrada. Serious thyroid adverse events were uncommon. A comprehensive risk management program with frequent lab monitoring will be implemented to support early detection and management of these autoimmune events.
The most common side effects of Lemtrada are infusion associated reactions (including headache, rash, fever, nausea, urticaria, pruritus, flushing and fatigue), infections (upper respiratory tract and urinary tract), lymphopenia and leukopenia.
Lemtrada is contraindicated in patients with Human Immunodeficiency Virus (HIV) infection.
Source: The Wall street Journal Copyright ©2013 Dow Jones & Company, Inc (17/09/13)
CHMP also Recommends NAS Designation for Aubagio® (teriflunomide) Following Positive Opinion on Approval in March 2013
Genzyme announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion for approval of Lemtrada™ (alemtuzumab) for the treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features.
In addition, the CHMP issued a positive opinion on new active substance designation (NAS) for Aubagio® (teriflunomide). Earlier this year, the CHMP issued a positive opinion recommending the approval of Aubagio for the treatment of adult patients with relapsing remitting MS.
The European Commission (EC) is expected to render a final decision to grant marketing authorizations for Lemtrada and Aubagio in the EU in the coming months.
“Today’s CHMP opinions set the stage for the approval of two important new treatment options for MS patients. Treatments to-date have addressed some of the unmet needs in MS, but still have limitations,” said David Meeker, MD, Genzyme President and CEO. “Upon approval, physicians will have the ability to prescribe Lemtrada for appropriate relapsing remitting patients based on their impressions of clinical or imaging characteristics regardless of duration of disease or treatment history. Expectations among the MS community are high for LEMTRADA and with today’s positive CHMP opinion we are a step closer to making this very innovative treatment available for MS patients in Europe.”
The positive CHMP opinion for approval of Lemtrada was based on data from the CARE-MS I and CARE-MS II trials, in which Lemtrada was significantly more effective than Rebif® (subcutaneous interferon beta-1a 44 mcg three times weekly) at reducing relapse rates. In CARE-MS II, accumulation of disability was significantly slowed in patients given LEMTRADA vs. Rebif, and importantly, patients treated with Lemtrada were significantly more likely to experience improvement in pre-existing disability.
“Today’s announcement from Genzyme represents a key milestone in the extensive program evaluating Lemtrada in multiple sclerosis,” said Professor Alastair Compston, Head of the Department of Clinical Neurosciences at the University of Cambridge, United Kingdom. “The superior efficacy of Lemtrada vs. Rebif in the clinical trials, which was sustained despite infrequent administration, represents an approach to treatment that promises to reshape the future for many people with active relapsing-remitting multiple sclerosis.”
Lemtrada 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 randomized Phase III studies comparing treatment with Lemtrada to Rebif in patients with relapsing-remitting MS 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. A large randomized Phase II study provided the foundation for the Phase III program.
Safety results were consistent across both the CARE-MS I and CARE-MS II studies. The most common adverse events associated with LEMTRADA were infusion-associated reactions, including headache, rash, fever, nausea and hives. Infections were common in both the Lemtrada and Rebif groups. Infections more common on Lemtrada treatment included upper respiratory and urinary tract infections, herpes viral infections, and influenza. Most infusion-associated reactions and infections were mild to moderate in severity and responded to standard treatments.
In both CARE-MS I and CARE-MS II, the incidence of serious adverse events was similar between the two treatment arms. As previously reported, autoimmune disorders were more frequent in patients treated with LEMTRADA, primarily autoimmune thyroid disease which was observed in an estimated 36% of patients during extended follow-up. Immune thrombocytopenia (ITP) developed in 1.4 percent of Lemtrada-treated patients through extended follow-up and 0.3% developed glomerulonephritis. Autoimmune disorders were detected soon after onset through a monitoring program, and were generally managed using standard treatments.
A comprehensive risk management program has been proposed to support early detection and management of adverse events.
In the U.S. the FDA has accepted for review the company’s supplemental Biologics License Application (sBLA) file seeking approval of Lemtrada (alemtuzumab) for the treatment of relapsing multiple sclerosis (RMS). FDA recently extended the review cycle for Lemtrada by three months; no additional clinical studies have been requested, therefore FDA action on the application is expected in late 2013.
Source: Genzyme (28/06/13)
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.
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.
Source: Chicago Tribune Health Copyright © 2013, Reuters (11/06/13)
The investigational drug alemtuzumab was effective in patients with highly active multiple sclerosis (MS), to the point that disease activity vanished in one-quarter, a researcher said here.
A subgroup analysis of data from the pivotal CARE-MS II trial, involving patients with multiple recent relapses and MRI-detected gadolinium-enhancing lesions at study entry, found an annualized relapse rate of 0.33 during the first 2 years of alemtuzumab (Lemtrada) treatment, compared with 0.65 for patients receiving interferon-beta-1a (Rebif), said Stephen Krieger, MD, of Mount Sinai School of Medicine in New York City.
The 51% reduction in relapse rate (P<0.0001) was virtually identical to the 49% decrease seen in the full CARE-MS II data reported last year, Krieger told attendees at the joint meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
The most stringent criteria for response -- no relapses, no sustained accumulation of disability, and no new gadolinium-enhancing lesions or new or enlarging T2 lesions -- were met by 24.2% of patients receiving alemtuzumab, compared with none of the interferon-beta control group, Krieger said.
Alemtuzumab is an anti-CD52 monoclonal antibody formerly sold as a cancer drug under the name Campath. In MS, it is believed to induce a shift in immune responsiveness to downregulate the T cell-mediated attack on myelin in the nervous system.
In the MS clinical trials, alemtuzumab was administered by infusion in an initial 5-day course, followed by a second 3-day course a year later. Two phase III trials testing alemtuzumab against interferon-beta-1a have been conducted: CARE-MS I in treatment-naive patients, and CARE-MS II in patients showing continued disease activity while on an approved disease-modifying MS drug.
Of the 667 patients in the latter study, 145 had what the investigators called highly active disease at enrollment -- at least two relapses in the previous year plus at least one gadolinium-enhancing lesion. Presumably, these would represent a more treatment-resistant group of patients.
The subgroup analysis generally supported that view. Response rates to both drugs were lower in the high-activity cohort than in the overall CARE-MS II data, in which the annualized relapse rates after 2 years were 0.26 and 0.52 for alemtuzumab and interferon, respectively.
Alemtuzumab consistently outperformed interferon in every other outcome measures Krieger reported for the highly active subgroup during the 2-year study (all P<0.001):
- Proportion with relapse: 36% alemtuzumab, 65% interferon
- Proportion with sustained reduction in disability: 31% alemtuzumab, 16% interferon
- Proportion without either relapse or sustained accumulation of disability: 61% alemtuzumab, 33% interferon
- Proportion MRI free of disease activity: 40% alemtuzumab, 8% interferon
- Safety findings were similar in the subgroup to what had been seen in other patients, Krieger said. Serious infections were somewhat more common with alemtuzumab (seen in 3.9% of patients, compared with 2.4% of the interferon control group).
- Serious infusion reactions were common, an effect not seen with interferon, which is given by subcutaneous injection.
No cases of autoimmune thrombocytopenia were seen in the analysis, Krieger said. Overall, he said, adverse effects with alemtuzumab were not "unexpectedly disproportionate" in the highly active subgroup.
There was one death in the subgroup -- a patient in the alemtuzumab arm who died in a traffic accident.
Alemtuzumab's developer, the Genzyme unit of Sanofi, has applied for U.S. marketing approval. A decision is expected this fall.
The study was funded by Genzyme/Sanofi and Bayer HealthCare.
Krieger reported relationships with both of those companies and also Acorda, Biogen Idec, EMD Serono, Novartis, Questcor, and Teva.
Primary source: CMSC-ACTRIMS Joint Meeting
Source reference: Krieger S, et al. "Alemtuzumab is efficacious in highly-active RRMS patients in CARE-MS II" CMSC-ACTRIMS 2013; Abstract DX01.
Source: MedPage Today © 2013 MedPage Today, LLC. (03/06/13)
Researchers think they may have figured out why a drug that is highly effective against one autoimmune disease can sometimes trigger another.
The CD52-targeted biologic drug alemtuzumab (Lemtrada) is in late-stage development for multiple sclerosis, with long-term efficacy shown with just two annual courses of treatment. But, in a few patients, the agent appears to prompt an autoimmune attack on the thyroid or other organs. The mechanism has been unclear.
A new study from researchers in Australia and China, published in Nature Immunology, suggests a possible answer. They found that T cells expressing CD52 downregulated other T cells in vitro. Also, examination of samples from human patients with type 1 diabetes (the autoimmune form) showed low counts of these CD52+ cells as well as impaired function in the few that did exist.
In another set of experiments in diabetes-prone young mice, injecting the animals with lymphocyte populations lacking the CD52+ subset resulted in accelerated development of diabetes.
The researchers suggested that depletion of CD52 T cells -- as occurs after alemtuzumab treatment -- may unleash other T cells to attack host tissues, resulting in autoimmune disease.
Source: MedPage Today © 2013 MedPage Today, LLC (20/05/13)
Looking ahead to a prospective FDA approval of its experimental multiple sclerosis drug Lemtrada and a new product launch into a competitive and fast-changing market, Genzyme executives today rolled out positive data from a one-year extension study of its pivotal Phase III trial that gives the company some boasting rights for a drug that demonstrated a durable response in most patients.
The bottom line of the extension data backs Genzyme's claim that the majority of the patients in the pivotal two-year trial continued to report that the disease was largely held in check for the following 12 months. Roughly 90% of the late-stage volunteers signed up for the extension study, with the understanding that they could receive additional treatment if they experienced a single relapse or the enlargement of at least two brain or spinal lesions. In the treatment naïve arm of the study, 65% of the patients receiving Lemtrada were relapse-free compared to 55% of the patients in another arm who had previously relapsed while using another treatment.
"In this 1-year extension study 80% of patients did not require an additional course of treatment, over 70% were stable or had improved disability scores," says Mike Panzara, therapeutic area head, multiple sclerosis and neurology. "This sends the message we are not going to be doing things in a me-too way. We're doing things that add value and move the field forward in treating the disease."
Genzyme is building on the successful showdown of Lemtrada vs. Rebif, a standard therapy for MS. Last November investigators reported that in a head-to-head study with Rebif (interferon beta-1a), Lemtrada was better at reducing the annualized rate of relapses, according to the trial results published in The Lancet. Also, the "accumulation of disability" was slower in the Lemtrada arm while an improvement in disability scores "suggested" a reversal of disability in some patients. Lemtrada is the commercial name for alemtuzumab, which had also been approved as Campath to treat leukemia. That cheaper drug, though, was shelved to make way for what is expected to be a far more expensive MS therapy.
If Lemtrada gets a green light from the FDA, though, it will be entering a roiled marketplace. Biogen Idec is likely nearing an OK for the oral MS drug Tecfidera (BG-12), which has been overshadowing Genzyme's new drugs--oral Aubagio and the infusion therapy Lemtrada. Aubagio, approved last September, has been prescribed by 80% of all MS specialists, says Bill Sibold, senior vice president, head of multiple sclerosis for the big Sanofi subsidiary. Most of those new patients are being switched from other treatments, with half coming from Avonex (Biogen Idec) and Copaxone, a mainstay at Teva Pharmaceutical Industries.
"I don't see any effect of Tecfidera on Lemtrada," says Sibold. "I consider them completely different animals." Lemtrada has had a "profound impact on disability, where patients not only slowed (the disease), some had improvements. That's something we haven't seen."
A thumb's up from the FDA in the second half of 2013 would come later than Genzyme had initially expected. Its first application to the agency was handed back last year for a rewrite, shoving the Sanofi drug further back in the queue. The FDA recently accepted the revised NDA for review.
Source: FierceBiotech © 2013 FierceMarkets (22/03/13)
Patients with rapid recovery of CD4-positive T cells after alemtuzumab treatment for multiple sclerosis (MS) are at risk for disease progression or relapse, research suggests.
The difference was apparent from 3 months after treatment, implying the potential for individualized treatment protocols based on CD4+ counts, say lead researcher Neil Robertson (Cardiff University, UK) and colleagues.
"The association between disease activity and early lymphocyte recovery is not surprising, as MS is primarily a cell-mediated disorder," they write in Neurology. "However, this relationship has not been demonstrated in vivo before."
The researchers assessed 56 patients (40 women) given alemtuzumab 12 mg daily for 5 days to treat symptoms of MS. They observed an initial "profound depletion" of lymphocyte subsets, followed by gradual recovery.
CD19+ cells were the first to recover, reaching the 25th percentile of average pretreatment levels at 3-6 months after treatment. These were followed by CD8+ cells, which reached a similar level after 6-9 months.
Patients' average CD4+ cell counts remained below the 25th of pretreatment levels for up to 24 months of follow up (they received a second alemtuzumab course 12 months after initial treatment). However, recovery of CD4+ cells differed between patients who did and did not exhibit disease activity during follow up.
In all, eight patients had a relapse, five had progressive disability, and four had asymptomatic lesions on magnetic resonance imaging. CD4+ cells were significantly higher at 6 and 24 months in patients with than without clinical relapse, and in those with than without new lesions.
CD4+ counts diverged from 3 months between patients who remained stable and those with any clinical or imaging measure of new disease activity, remaining significantly higher in those with disease activity through 24 months.
Having a 12-month CD4+ count above 400x106/mL was 81.1% sensitive and 73.7% specific for new disease activity by 24 months. "Current practice is to routinely image all patients at 24 months and to base treatment decisions on these scans and available clinical data," say Robertson et al.
They note that the high negative predictive value of a low CD4+ count suggests that retreatment could potentially be restricted to patients with higher counts. "Inevitably this would be attractive in managed care programs and environments where access to imaging is difficult and this economic argument could be built on if larger studies support this assertion."
Source: News-Medical.Net (19/12/12)
Medical journal The Lancet warned that Sanofi's experimental multiple sclerosis drug Lemtrada may be too costly for patients and health insurers once it gets approved by regulators.
The journal, which published the encouraging results of two late-stage Lemtrada tests on Thursday, also criticized the drugmaker's decision to withdraw leukemia therapy Campath, the same drug given at a different dosage, depriving MS patients who had been using it off-label.
In an editorial accompanying the test results, The Lancet voiced concerns that Lemtrada would be priced higher than current MS drugs on the market and said the discontinuation of Campath may mean patients who had used it for MS would not be able to continue their treatment.
The injectable drug, chemically known as alemtuzumab, was sold until September 2012 under the name Campath as treatment for leukemia and given more frequently at a higher dosage.
"There is concern that with a license for multiple sclerosis, the cost of alemtuzumab could rise and might become too expensive for many patients and health systems," the editorial said.
Although Campath remains available free of charge to leukemia patients, Sanofi's rare disease unit Genzyme pulled it off the market in September to prevent its unauthorized use as an MS drug.
Analysts said the move would allow the company to adjust the price to match that of rival MS drugs on the market.
A full course of Campath, which in 2011 had sales of $76 million, cost around $60,000 when given three times a week for up to 12 weeks, according to Genzyme.
Lemtrada, instead, is given at less than half the dose of Campath for 5 consecutive days and then again for 3 days a year later. Since the drug has yet to be approved, it remains unclear how much Sanofi will charge for it.
The drug, which works by resetting a person's immune system, has shown in late-stage trials to be an effective treatment for MS patients who have failed to respond to other therapies.
It has also shown to benefit people not previously treated for the disease, suggesting it could be used as a first-line MS therapy.
But patients need regular monitoring for serious side effects that can include infections and autoimmune diseases.
"It's important that the appropriate safety monitoring is in place for patients who are prescribed Lemtrada," Genzyme's head of MS, Bill Sibold, told Reuters, responding to questions about the Lancet editorial. "Until an approved risk-management program is established, we believe the use of Lemtrada should only occur in clinical trials."
Lemtrada remains available to patients who are taking part in clinical tests.
Sibold declined to discuss pricing plans for Lemtrada, but said Genzyme has set up programs to make its approved drugs available to patients who cannot afford them. "With Lemtrada it would be no different," he said.
But there are concerns that cash-strapped European governments may balk at funding the drug through their public healthcare systems.
Doug Brown, Head of Biomedical Research at U.K. charity MS Society said that while Lemtrada's results are great news for patients, the drug would only be useful to them if it were available through the country's publicly funded National Health Service.
"We urge Genzyme to price the treatment responsibly so that if it's licensed, it's deemed cost effective on the NHS," he said.
The U.K.'s cost-effectiveness body National Institute for Health and Clinical Excellence (NICE), whose opinions are also watched closely in other countries, initially rejected Novartis' MS pill Gilenya, only to make a U-turn after the company agreed to a discounted price.
Sanofi launched its MS pill Aubagio in the U.S. at a price of $45,000 for a year's treatment, making it cheaper than rivals.
Gilenya - the only other MS pill currently on the market - costs 28 percent more, while injectable treatments such as Biogen Idec Inc's Avonex and Teva Pharmaceutical Industries Ltd's Copaxone are 8 and 6.5 percent higher respectively.
Source: Reuters © 2012 Thomson Reuters (01/11/12)
Two new trials offer proof that a leukemia drug long used to treat multiple sclerosis works better than a common treatment.
When compared with the widely used drug interferon beta, the leukemia drug alemtuzumab reduced relapse rates by half, researchers say.
Alemtuzumab Reverses Disability in Some
Alemtuzumab has been used to treat MS for close to two decades, but it has never been approved for this use. It is given by IV infusion.
The drug not only reduced relapses, but improved disability associated with MS, such as loss of coordination or difficulty walking, in some patients.
Side effects include infusion reactions, infections, and potentially serious autoimmune disorders. Patients taking it must be followed closely.
“In the menu of treatment choices for MS patients, I think alemtuzumab falls into the ‘high-reward, high-risk’ category,” says Alasdair Coles, MD, of Britain’s University of Cambridge, who led one of the newly published studies.
“No other drug has been shown to offer the benefits in terms of disability improvement that this drug shows,” he says. "It comes with problems, but these problems are manageable.”
400,000 MS Patients in U.S.
The National MS Society estimates that about 400,000 people in the United States have been diagnosed with multiple sclerosis, and most (85%) have the relapsing-remitting form of the disease, in which symptoms come and go.
These symptoms can include loss of feeling, coordination, and mobility, problems with thinking and vision, and depression.
In one of the two newly published studies, University of Cambridge researchers followed 563 previously untreated patients treated with either alemtuzumab or interferon beta.
Two years later, 22% of the alemtuzumab-treated patients had relapsed, compared to 40% of those treated with interferon beta.
In the second study, which included 840 patients whose MS symptoms were not being controlled with other treatments, treatment with alemtuzumab was associated with 35% of patients relapsing over two years, compared to a 51% relapse rate among those treated with interferon beta.
Patients in this study were also less likely to have additional MS-related disabilities after two years when they took alemtuzumab; 13% had disabilities compared to 20% of interferon-treated patients.
1 in 3 Users Develop Autoimmune Disease
In clinical practice, alemtuzumab has most often been used to treat patients who don't respond to other treatments or are no longer responding to them.
Coles says he believes this is how the drug will continue to be used if it is approved as an MS drug in the U.K. and the U.S.
He adds that about 1 in 3 patients who take the drug for MS develop an autoimmune disorder that affects the thyroid, and about 1 in 100 develop a disorder that involves blood platelets, which are involved in clotting and stopping bleeding.
He says both conditions, while potentially serious, can be easily managed if patients are followed closely.
“Close monitoring is critical because these side effects tend to appear a year or two after treatment, when MS symptoms are often under control and patients want to get on with their lives,” he says.
National MS Society Chief Research Officer Tim Coetzee, PhD, says he does not see this as a big deterrent, since many of the newer drugs for multiple sclerosis also require close monitoring.
“Given the choice between having a treatment that requires aggressive monitoring and not having that treatment at all, I believe that most patients will take the treatment any day of the week,” he says.
Drug’s Cost as MS Treatment in Question
The drug maker Genzyme plans to market alemtuzumab as an MS treatment in the U.S. and Europe, pending approval by government regulators. The drug will not be available to MS patients during the approval process.
In an editorial published with the two studies, editors of the journal Lancet express concerns that the drug will be too expensive for patients and health systems when it is reintroduced as an MS treatment.
“Finding promising treatments such as alemtuzumab is important,” they write. “But so is keeping alemtuzumab accessible and affordable if its early success in these trials proves to be of enduring value.”
Source: WebMD ©2005-2012 WebMD, LLC (01/11/12)
Pharmaceutical giant Sanofi withdraws existing treatment to boost profits with rebranded Lemtrada.
A pharmaceutical company stands accused of putting profit before patients after withdrawing a drug used in the treatment of a chronic debilitating disease – ahead of relaunching it at a price predicted to be up to 20 times higher.
Three of Britain's leading neurologists have written to the Health Secretary, Jeremy Hunt, to protest at Genzyme, part of the multinational drug company Sanofi, halting supplies of the drug alemtuzumab for multiple sclerosis.
The drug is currently licensed for the treatment of leukaemia. But it has been known for 20 years also to be effective in MS patients suffering from an aggressive form of the disease.
Neurologists have used the drug in these patients "off label" – prescribing it on their own initiative even though it was not licensed for multiple sclerosis – following encouraging results from a large placebo-controlled trial published in the New England Journal of Medicine in 1998. Alemtuzumab, which is given in two courses a year apart, costs markedly less than other drugs for multiple sclerosis to which it is thought to be superior – around £2,500.
Genzyme has now applied for a licence for the drug in multiple sclerosis to regulators in Europe and the US and is expected to relaunch it under the trade name, Lemtrada, at what could be many times its current price. In the meantime the company has withdrawn the drug from MS patients' off-label treatment, pending the granting of the licence, on the grounds that "any adverse event outside a clinical trial … may complicate the regulatory process".
In the neurologists' letter to the Health Secretary, professors Neil Scolding of the University of Bristol, Neil Robertson of the University Hospital of Wales and John Zajicek of the University of Plymouth say that Genzyme's decision has "serious implications for vulnerable UK patients with MS". They say patients who have already started treatment will "not be able to get their vital second course", and new patients may "miss their window of therapeutic opportunity" putting them at risk of "progressive, severe disability".
When licensed, they say, the drug's price is expected to be "15 to 20 times greater", and its withdrawal sets an "inappropriate precedent". They add: "It shows little regard for patients whose opportunity to alter the course of their disease is time-limited, and may represent an over-enthusiastic attempt by the parent company to profit from the current situation."
Professor Zajicek said he had personally treated about 150 patients with the drug, and 400 to 500 had received it across the UK. "Many of us think it is the best drug for patients with aggressive MS in the early stages of the disease. It's the greedy behaviour of the drug company that upsets me. They are just trying to rebrand it and put the price up. It is morally corrupt."
A spokesperson for Genzyme said: "Our goal is to ensure that Lemtrada is approved by regulatory authorities and made available to multiple sclerosis patients as quickly as possible. Until approved risk-management programmes are established, the use of Lemtrada for MS should occur only in clinical trials. Off-label use of alemtuzumab in MS has always been at the discretion of individual clinicians without reference to the company."
"In the UK, our price for Lemtrada and the value it brings to patients will be subject to the usual health economic evaluation by the National Institute for Health and Clinical Excellence."
Doug Brown, Head of Biomedical Research at the Multiple Sclerosis Society, said: "Alemtuzumab shows real promise as a potentially new medicine for many people with relapsing-remitting MS. There is no good reason why people with MS who have been allowed to benefit from the treatment should now be denied it.
"Genzyme need to come up with a scheme, quickly, that makes their product available to all those people currently being treated and, if it's licensed, price the drug reasonably so it is deemed cost effective on the NHS."
A Department of Health spokesperson said: "We know how important this drug is for some MS sufferers and are working closely with the company and the NHS to help make sure these patients can still access it."
Case study: 'I have seen the way my mother is suffering'
Oritse Williams, 25, of the platinum-selling boyband JLS, knows the suffering caused by multiple sclerosis since his mother, Sonia, 54, was diagnosed over a decade ago. He and his brother pledged when in their teens that they would do all they could to help her.
"We decided that when we grew up, my brother would become a scientist and I would try to make money from my music. That way we would have both the means and the ability to find a cure." Williams cared for his mother through his childhood and until he appeared in the final of The X Factor in 2008.
The drugs company: Sanofi
Sanofi, based in Paris, is the world's fourth-largest pharmaceutical company, employing 113,000 people worldwide.
Last year the company made a profit of almost €6bn on revenue of €33b. Its products include Clomid, for female infertility, the anti-clotting agent Plavix and the cancer drug Taxotere.
The company is the world's largest producer of vaccines through its subsidiary Sanofi Pasteur. It acquired Genzyme, a US biotech company based in Cambridge, Massachusetts, in 2011.
In 2010 Sanofi sacked 1,700 US employees citing growing competition from non-branded generic manufacturers. It denied the action was related to its purchase of Genzyme.
Last week, the Paris-based company announced plans to cut almost 1,000 jobs in France despite protests condemning the move.
Source: The Independent © independent.co.uk (15/10/12)
FDA refuses MS drug Lemtrada filing(28/08/12)
Genzyme, a Sanofi company, announced it has received a Refuse to File letter from the U.S. Food and Drug Administration (FDA) in response to the supplemental Biologics License Application (sBLA) for the approval of Lemtrada™ (alemtuzumab) as a treatment for relapsing multiple sclerosis.
After collaborative consultations with the FDA, the agency requested that the company modify the presentation of the data sets to enable the agency to better navigate the application. The FDA has not requested additional data or further studies. Genzyme will work with the FDA over the coming weeks to resubmit the application as soon as possible.
“We have had constructive dialogue with the FDA, and we are very confident in our ability to address the agency’s request and resubmit rapidly,” said David Meeker, President and CEO, Genzyme.
The company’s marketing authorization application submitted to the European Medicines Agency has been accepted and the review process is underway.
Genzyme is developing Lemtrada in MS in collaboration with Bayer HealthCare.
Alemtuzumab is a monoclonal antibody that selectively targets CD52, a protein abundant on T and B cells. Treatment with alemtuzumab results in the depletion of circulating T and B cells thought to be responsible for the damaging inflammatory process in MS. Alemtuzumab has minimal impact on other immune cells. The acute anti-inflammatory effect of alemtuzumab is immediately followed by the onset of a distinctive pattern of T and B cell repopulation that continues over time, rebalancing the immune system in a way that potentially reduces MS disease activity.
Genzyme holds the worldwide rights to alemtuzumab and has primary responsibility for its development and commercialisation in multiple sclerosis. Bayer HealthCare retains an option to co-promote alemtuzumab in multiple sclerosis. Bayer HealthCare has notified Genzyme of its intention to co-promote under this option. Upon regulatory approval and commercialization, Bayer would receive contingent payments based on sales revenue.
*LemtradaTM is the proprietary name submitted to health authorities for the company’s investigational multiple sclerosis agent alemtuzumab.
Source: Therapeutics Daily ©2011 UBM Canon (28/08/12)
Sanofi's rare disease unit Genzyme is pulling leukaemia drug Campath to prepare for its launch under a different dosage and as a multiple sclerosis treatment that will be branded as Lemtrada.
The withdrawal, meant to prevent the off-label use of Campath as a multiple sclerosis drug, is already under way in some European countries and will be effective in the United States on September 4, a Genzyme spokesman said.
Lemtrada, which Sanofi submitted for approval with health regulators in Europe and the United States in June, could be launched in 2013 if it wins approval.
If approved, it will be given far less frequently and in lower doses than Campath, and is one of the new products the French drugmaker is betting on to restore growth after losing several aging blockbusters to generic rivals.
"We think that this stoppage shows Sanofi's confidence in the approval of Lemtrada in multiple sclerosis," said Bryan Garnier analyst Eric Le Berrigaud, who estimates the drug could generate sales of $400 million in 2018, if approved.
The withdrawal will also enable Sanofi to adjust Lemtrada's price closer to that of rival multiple sclerosis drugs, Le Berrigaud said. Rivals include Tysabri, an injectable drug sold by Biogen Idec and Elan, while Novartis markets MS pill Gilenya.
Campath, which last year had sales of $76 million, will continue to be available through patient access programs in the 50 countries where it has been available since its launch in 2001.
"In most countries we will provide the drug for free, where this is permitted," the Genzyme spokesman said.
The news was first reported by trade publication BioCentury.
Source: Chicago Tribune © Chicago Tribune 2012 (22/08/12)