Sanofi: Defense In Depth
54, Rue La Boetie
75008 Paris, France
Telephone: +33 (0)1 53 77 40 00
Website: sanofi.com
Best-Selling Products
| PRODUCT | 2013 SALES | 2012 SALES |
|---|---|---|
| Lantus | $7,590 | $6,587 |
| Plavix/Iscover | $2,466 | $2,744 |
| Lovenox | $2,262 | $2,514 |
| Polio/pertussis/Hib Vaccines | $1,525 | $1,572 |
| Influenza vaccines | $1,234 | $1,174 |
| Avapro/Aprovel, CoAprovel | $1,171 | $1,529 |
| Renagel, Renvela | $996 | $867 |
| Cerezyme | $914 | $841 |
| Myozyme, Lumizyme | $664 | $614 |
| Meningitis/Pneumonia vaccines | $659 | $863 |
| Taxotere | $543 | $748 |
| Allegra | $539 | $734 |
| Depakine | $538 | $545 |
| Adult booster vaccines | $519 | $659 |
| Ambien/Stilnox/Myslee | $519 | $660 |
| Fabrazyme | $509 | $388 |
| Travel and other Endemics vaccines | $508 | $483 |
All sales are in millions of dollars and were translated using the Federal Reserve Board’s average rate of exchange in 2013: €1.3281.
Financial Performance
| 2013 | 2012 | |
|---|---|---|
| Revenue | $43,762 | $46,413 |
| Net income | $5,146 | $6,718 |
| EPS | $3.69 | $4.89 |
| R&D expense | $6,335 | $6,514 |
| 1H 14 | 1H 13 | |
|---|---|---|
| Revenue | $21,139 | $21,332 |
| Net income | $2,553 | $2,020 |
| EPS | $1.87 | $1.45 |
| R&D expense | $3,090 | $3,110 |
All sales are in millions of dollars except EPS and were translated using the Federal Reserve Board’s average rate of exchange in 2013: €1.3281.
Unlike most of its American counterparts in the midst of various degrees of contraction and narrowing focus, Sanofi continues to do pretty much everything. The company is still competing across the entire scope of the pharmaceutical marketplace, from the broad-market blockbuster (Lantus, the word’s leading diabetes brand) to the old cardiovascular classics (Plavix and Lovenox remain popular overseas even after losing U.S. exclusivity) to specialty drugs (Renagel, closing in on blockbuster status) to rare disorders (Cerezyme, Myozyme, Fabrazyme) to vaccines (Sanofi Pasteur remains the largest company in the world devoted entirely to vaccines).
But even the broadest market approach does not spare a modern pharmaceutical company from the occasional run of patent expirations, and that is what happened to Sanofi in 2013. Executives estimate that the company lost about €1.27 billion ($1.69 billion) in revenue to generic competition in 2013, mostly related to flagship products such as Plavix, Avapro/Aprovel, Eloxatin, and Lovenox.
Sanofi’s “cliff” period, though, is largely over. And the company’s pipeline is, if anything, even broader in scope than its presently marketed portfolio, including late-stage compounds for ranging from autoimmune disorders and dermatitis to cholesterol and diabetes, not to mention new vaccines for Clostridium difficile and dengue. With all this in hand plus the continued growth of Lantus – which could exceed $8 billion in sales in 2014 – Sanofi executives sound confident about their company’s future.
“I think we were able to demonstrate that some of the issues that we faced in 2013 have been resolved and really I think we are able to demonstrate that return to growth,” says Sanofi CEO Christopher Viebacher. “Based on the solid momentum in our late-stage pipeline, we are actively preparing for a wave of new product launches that will further redefine Sanofi as a biopharmaceutical leader.”
Sanofi’s top-line revenue in 2013 totaled €32.95 billion ($43.76 billion), down 5.7 percent from the previous year. Net income for the year was €3.88 billion ($5.15 billion), a drop of 23.4 percent, while earnings per share decreased 90 cents to €2.78 ($3.69). Spending on research and development for the year was €4.77 billion ($6.34 billion), 2.8 percent less than 2013. In the first half of 2014, the company’s revenue was €15.92 billion ($21.14 billion), a decrease of 0.9 percent, while net income rose 26.4 percent to €1.92 billion ($2.55 billion) and EPS improved to €1.41 ($1.87). Company leaders are projecting full-year EPS at between €2.95 and €3.00 ($3.92 and $3.98).
Acquisitions And Partnerships
In September 2013, Sanofi and Aviesan, the French National Alliance for Life Sciences and Health, renewed for a period of three years the cooperation protocol signed in 2010. The aim of the renewal is to contribute to the development of new treatments that target unmet medical needs, including those in the field of rare diseases, to participate to the excellence and consolidation of research in French industry on an international level. Special emphasis will be put on translational research projects that bring together clinical and medical teams with fundamental research teams to translate research successes into medical advances.
Several projects under this new protocol are under discussion, including the creation of centers of excellence as part of future investments, particularly in collaboration with IHUs (University Hospital Institutes) and IRTs (Technological Research Institutes). The new cooperation between Aviesan and Sanofi research teams will also spur the development of technology platforms to finance the work of researchers (e.g. the ATIP-Avenirs program), CIFRE fellows, post-docs, and staff secondment.
“With the signing of several projects between Sanofi and Aviesan during the past three years, Sanofi has become the leading private partner of academic research in the life sciences,” says Dr Elias Zerhouni, president, Global Research & Development, Sanofi. “Strategic and operational committees have worked tirelessly to achieve this convergence of the best in French academic excellence and our own teams. We all committed to pursuing these vital interactions in order to accelerate scientific discoveries for the benefit of patients.”
In October, Sanofi Pasteur – the vaccines division of Sanofi – launched a partnership with the Bill & Melinda Gates Foundation to explore and develop new platforms and methods intended to accelerate vaccine R&D, particularly in areas of global health. The Vaccine Discovery Partnership (VxDP) is a newly created, formal mechanism by which the Gates Foundation can directly collaborate with Sanofi Pasteur and other vaccine-pharmaceutical companies across disease areas of interest. It provides an integrated, straight-forward and sustained relationship based on a memorandum of understanding (MOU).
“The MOU with the Gates Foundation facilitates our working together to de-risk novel concepts, technologies, platforms, and approaches of mutual interest,” says John Shiver, Ph.D., senior VP of R&D for Sanofi Pasteur. “This program provides a mechanism to pursue R&D of new candidate vaccines for global health in the preclinical and clinical phases up to and including Phase IIa clinical trials.”
According to Shiver, the partnership allows the Gates Foundation and its pharmaceutical partners to accelerate the development of candidate vaccines for use in developing countries, while allowing the pharmaceutical partners to develop and test new technologies that also will advance their other R&D programs. This VxDP spearheaded by the Gates Foundation is expected to result in decreased cost and time required to develop successful vaccines. Sanofi Pasteur has already been working with the Gates Foundation on other projects such as HIV vaccine development and distributing inactivated (as opposed to oral) polio vaccines globally to eradicate the disease.
In December, Sanofi and Regeneron Pharmaceuticals Inc. announced a collaboration with the American College of Cardiology focused on enhancing clinical research with alirocumab, an investigational monoclonal antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9). PCSK9 is known to contribute to circulating low density lipoprotein cholesterol (LDL-C) levels. The compound is being jointly developed by Sanofi and Regeneron.
Under the terms of the agreement, the ACC will apply its expertise in clinical research and utilize its extensive registries to identify patients who might be appropriate candidates for the Phase III ODYSSEY OUTCOMES clinical trial. This Data Driven Trial Recruitment Program is a new approach to identification and recruitment of patients for the clinical trial. Additional activities under the collaboration include a comprehensive educational program for both physicians and patients.
“Through this collaboration, we hope to provide better access to our Phase III ODYSSEY OUTCOMES trial,” says Jay Edelberg, M.D., Ph.D., VP, PCSK9 Development and Launch Unit, Sanofi. “This is the first time that ACC’s PINNACLE Registry will be used for clinical trial recruitment, and we believe this novel approach will help trial sites meet and hopefully exceed their recruitment goals.”
In January, Genzyme and Alnylam Pharmaceuticals Inc. expanded their strategic agreement to develop and commercialize treatments for rare genetic diseases. Genzyme will have significant rights to Alnylam’s portfolio of clinical and pre-clinical stage drug candidates. Alnylam will retain most product rights in North America and Western Europe, and will have significantly expanded development and commercial opportunities for its genetic medicine pipeline through Genzyme’s established global infrastructure in rare diseases.
“This collaboration is an important building block for our future,” says David Meeker, M.D., Genzyme’s president and CEO. “It strengthens our pipeline and provides us with the opportunity to meet the needs of patients with rare diseases around the world through our well-established global organization. This transaction also powerfully underscores Sanofi’s commitment to investing in Genzyme as one of the company’s key growth drivers. Our partnership with Alnylam has been highly collaborative, and their world-class RNAi technology holds the promise to provide a platform for sustained drug development for rare genetic diseases for years to come.”
In 2012, Alnylam and Genzyme formed an exclusive alliance to develop and commercialize Alnylam’s lead product, patisiran, which is in Phase III development for the treatment of transthyretin (TTR)-familial amyloid polyneuropathy, a rare life-threatening disease that damages the nervous system.
The expanded relationship between Genzyme and Alnylam includes four major components. First, Genzyme will obtain expanded rights to patisiran. Under the original agreement from 2012, Genzyme had rights to commercialize patisiran in Japan and the broader Asia-Pacific region. This disease has a disproportionately high prevalence in these territories. Under the expanded agreement, Genzyme will now commercialize patisiran in all territories outside of North America and Western Europe, which are retained by Alnylam for their commercialization.
Second, Genzyme will obtain rights to commercialize worldwide three products in Alnylam’s pipeline. Specifically, Genzyme and Alnylam will co-develop and co-commercialize ALN-TTRsc – a product in Phase II development for the treatment of familial amyloid cardiomyopathy – in North America and Western Europe, while Genzyme commercializes the product in the rest of world; Genzyme will have the rights to two additional products after the completion of early clinical trials and will be able to choose between full global rights or co-commercialization rights, depending on the product.
Third, Genzyme will have the option up until 2020, with the possibility of extension through the end of 2021, to develop and commercialize outside of North America and Western Europe all products being developed to treat rare genetic diseases from Alnylam’s pipeline. Alnylam retains its rights to co-develop and co-commercialize its genetic medicine pipeline in North America and Western Europe.
Additionally, Genzyme will become a major Alnylam shareholder with a stake of 12 percent through a $700 million investment at a price of about $80 per share, which represents a 27 percent premium as compared to the average share price over the 30 days before the transaction. Alnylam will receive R&D funding, starting on Jan. 1, 2015, for programs where Genzyme has elected to opt-in for development and commercialization. Further, Alnylam is eligible to receive milestones and royalties.
Also in January, Sanofi and Fraunhofer-Gesellschaft – one of Europe’s leading organizations for applied research – announced the creation of a natural product center of excellence to accelerate the discovery and development of new therapies to treat infectious diseases. Such diseases are the second leading cause of mortality worldwide.
Under the agreement, Sanofi and Fraunhofer IME (Institute for Molecular Biology and Applied Ecology) will collaborate to identify and optimize novel naturally occurring chemical or biological compounds, mainly in the field of infectious diseases. The approach may also be extended to other indications such as diabetes, pain, and rare diseases, where natural products derived substances have proven to play an important role in treatment and disease prevention. Sanofi will share its strain collection, which is one of the world’s largest with over 100,000 different microorganisms, with Fraunhofer, and in addition is bringing its know-how in anti-infective research.
“There is a great medical need in fighting infectious diseases globally,” Dr. Zerhouni says. “This is critical given the rise of antibiotic resistance worldwide especially in the hospital setting with increasingly frequent serious, often life-threatening infections, where few advances have been made in the recent years. This cooperation with Fraunhofer is unique as internal and external scientists will work together as one team on common projects, in shared labs to acquire new knowledge with the objective to bring new medicines to patients suffering from infectious diseases.”
In March, Sanofi and UCB entered into a scientific and strategic collaboration for the discovery and development of innovative anti-inflammatory small molecules, which have the potential to treat a wide range of immune-mediated diseases in areas such as gastroenterology and arthritis. Under the terms of the agreement, Sanofi and UCB will share costs and profits on a 50/50 basis. UCB will be entitled to initial upfront, preclinical and clinical development milestone payments from Sanofi, potentially exceeding €100 million.
“Immune-mediated diseases affect individuals, families, and communities and impact the economies of countries and nations, making this poorly understood category of diseases a significant public-health burden,” Dr. Zerhouni says. “Joining efforts with UCB, we will address a scientific challenge in immunology, and increase the chances of accelerating the discovery and development of future therapies.”
In June, Sanofi and Medtronic Inc. signed a memorandum of understanding to enter into a global strategic alliance in diabetes, aimed at improving patient experience and outcomes for people with diabetes around the world. The alliance will initially focus on two key priorities: the development of drug-device combinations and delivery of care-management services to improve adherence, simplify insulin treatment, and help people with diabetes better manage their condition.
The alliance will be structured as an open-innovation model, taking advantage of the capabilities, as well as the human and financial resources, of both companies. Based on the success of the two initial priorities, the companies may explore other areas for potential collaboration. Sanofi and Medtronic already have an agreement in place serving specific Type 1 diabetes patients in Europe with an implantable insulin delivery system, and intend to add this project and additional innovative projects to the alliance.
“We know that insulin and other medicines are only one element of treating the whole patient,” says Pascale Witz, executive VP of Global Divisions & Strategic Development, Sanofi. “There is no day off in managing diabetes, and lack of adherence is one of the major hurdles to optimal disease management. That is why Sanofi is committed to developing integrated care solutions that focus on making life easier for people with diabetes and improving clinical outcomes that may help reduce costs to the overall healthcare system. Through this important collaboration, Sanofi will tap into technology advances that aim to create holistic treatment solutions which take into account the individual patient’s needs.”
The alliance will pair Sanofi’s extensive insulin portfolio and drug development expertise with Medtronic’s expertise in insulin pumps and continuous glucose monitoring. One of the priorities of the alliance will be to deliver novel drug-device combinations, including new form factors that are affordable, convenient and easy to-use to increase therapy adherence and deliver better outcomes. These efforts will focus on improving the management of Type 2 diabetes, especially for people who cannot achieve glucose control even with multiple daily injections of insulin.
Care-management services, another priority area for collaboration, will be delivered through a program designed to guide people with Type 2 diabetes who are failing to achieve disease control on oral therapies through the initiation phase of insulin treatment. Insulin initiation can be challenging as a high number of patients drop insulin treatment in this early phase.
In August, Sanofi and MannKind Corp. entered into a worldwide exclusive licensing agreement for development and commercialization of Afrezza Inhalation Powder, a new rapid-acting inhaled insulin therapy for adults with type 1 and type 2 diabetes. The companies plan to launch Afrezza in the United States in the first quarter of 2015.
Sanofi is responsible for global commercial, regulatory, and development activities. Under a separate supply agreement, MannKind will manufacture Afrezza at its manufacturing facility in Danbury, Conn. In addition, the companies are planning to collaborate to expand manufacturing capacity to meet global demand as necessary.
MannKind will receive an upfront payment of $150 million and potential milestone payments of up to $775 million. The milestone payments are dependent upon specific regulatory and development targets, as well as sales thresholds. Sanofi and MannKind will share profits and losses on a global basis, with Sanofi retaining 65 percent and MannKind receiving 35 percent. Sanofi has agreed to advance to MannKind its share of the collaboration’s expenses up to a limit of $175 million.
“Afrezza is an innovative drug-device combination product consisting of a dry formulation of human insulin delivered through a small, discreet inhaler,” says Pierre Chancel, Sanofi senior VP Diabetes Division. “Afrezza is a further addition to our growing portfolio of integrated diabetes solutions. It is uniquely positioned to provide patients with another insulin therapy option to manage their diabetes but does not require multiple daily injections.”
In September, Sanofi and MyoKardia Inc., a privately held company developing precision therapies for genetic heart disease, launched a worldwide collaboration to discover and develop first-of-its-kind targeted therapeutics for heritable heart diseases known as cardiomyopathies, the most common forms of heart muscle disease. The collaboration encompasses three MyoKardia programs. Two of these programs are focused on hypertrophic cardiomyopathy and the other is focused on dilated cardiomyopathy. The collaboration provides up to $200 million in equity investments, milestone payments, and research and development services through 2018, of which $45 million has already been received in an upfront licensing fee and an initial equity investment. In addition, Sanofi and MyoKardia will equally share development costs on the HCM programs following initial demonstration of efficacy in patients, with Sanofi fully covering the development costs of the DCM program. The collaboration is an outgrowth of Sanofi’s Sunrise initiative, a strategic partnership model that seeks to invest in early-stage opportunities that align with Sanofi’s expert development and commercialization abilities.
“This collaboration illustrates Sanofi’s research and development philosophy for Sunrise projects,” Dr. Zerhouni says. “It combines in a meaningful way the unique expertise in rare and cardiovascular diseases of our top scientists with that of the best innovators in the world, like MyoKardia’s founders and scientists, to achieve real breakthroughs in medicine.”
Product Performance
Lantus remained solidly atop Sanofi’s revenue charts in 2013, enjoying 15.2 percent growth and rolling up a total of €5.72 billion ($7.59 billion) in sales. The product is the No. 1 selling insulin brand in the world in terms of both sales and units and is available in more than 120 countries. The clock may soon run out on Lantus’ growth, though; Sanofi’s exclusivity is set to expire in February 2015 in the United States, May 2015 in Europe, and November 2014 in Japan. Since Lantus is a biologic though, the impact of its exclusivity cliff remains to be seen. Several companies are working on Lantus generics, but Sanofi has already launched litigation against one of them – Lilly – and, according to published reports, a Lantus bioequivalent will likely not see the light of day until at least 2016. In the first half of 2014, sales of Lantus were up another 9.4 percent to €3.01 billion ($3.99 billion).
Sales of the cardiovascular drug Plavix/Iscover fell by 10.1 percent in 2013 to €1.86 billion ($2.47 billion), but Sanofi executives are likely viewing this as a victory given that the drug lost its U.S. exclusivity back in May 2012. The impact of the U.S. exclusivity loss was largely made up by growth in China (14.3 percent) and Japan (13.3 percent), which together now account for nearly two-thirds of Plavix sales worldwide. In the first half of 2014, Plavix sales fell another 3.3 percent to €912 million ($1.21 billion), with growth in China and Japan again wiping out most of the negative impact of generic competition, this time in Western Europe.
The low molecular weight heparin Lovenox was another victim of generic competition in 2013, with sales dropping by 10 percent to €1.7 billion ($2.26 billion) due to generics in the U.S. market. The United States accounts for only 11 percent of the Lovenox market, though; in Western Europe (just over 50 percent of the total), sales actually rose by 0.9 percent. In the first half of 2014, Lovenox sales totalled €837 million ($1.11 billion), a drop of 3.1 percent, with growth in Western Europe and emerging markets largely offsetting the decline in the United States.
Sales of Sanofi’s polio/pertussis/Hib vaccine portfolio fell off slightly in 2013, dropping 3 percent to €1.15 billion ($1.53 billion). This reflected a good performance in emerging markets, which grew by 33.9 percent and accounted for more than half the total, but also a decline in sales of 23.8 percent in the United States triggered by supply limitations for Pentacel and Adacel lasting from April 2012 until October 2013. This situation nearly reversed itself in the first half of 2014; sales of the portfolio dropped 12.1 percent to €495 million ($657 million) on lower sales in emerging markets due to delays in shipments of Pentaxim, partially offset by the resumption of Pentacel supplies in the United States.
The company’s influenza vaccine portfolio enjoyed 5.1 percent growth in 2013, rising to €929 million ($1.23 billion) in sales with the assistance of 20.4 percent growth from the Fluzone family in the United States. The portfolio performed even better in the first half of 2014, with sales up by 12.8 percent to €194 million ($258 million) due to seasonal vaccination campaigns in the emerging markets.
Sales of the antihypertensives Avapro/Aprovel and CoAprovel dropped 23.3 percent to €882 million ($1.17 billion) in 2013, mainly due to generic competition in Western Europe. The first half of 2014 has brought more of the same, with franchise sales down 22.3 percent to €372 million ($494 million).
Renagel, used to treat hyperphosphatemia in patients with chronic kidney disease, generated sales of €750 million ($996 million) for Sanofi in 2013, an improvement of 14.9 percent. This was driven primarily by growth of 22 percent in the United States, which accounted for more than two thirds of Renagel sales. In the first half of 2014, Renagel sales were down 10.7 percent to €309 million ($410 million), reflecting the impact of an agreement with Impax that allowed that company to sell a limited number of authorized generics of the drug in the United States from April 2014 onwards.
The Gaucher disease drug Cerezyme improved its sales by 8.7 percent to €688 million ($914 million) in 2013, pushed along by 36.3 percent growth in emerging markets, which now account for more than a third of the product’s sales. In the first half of 2014, Cerezyme sales totaled €343 million ($456 million), an improvement of 0.3 percent.
Fabrazyme, indicated for the treatment of Fabry disease, enjoyed an impressive 31.2 percent bounce in 2013 with total sales of €383 million ($509 million), mainly due to an increase in the number of new patients in the United States and Western Europe. In the first half of 2014, Fabrazyme sales rose another 20.8 percent to €221 million ($294 million).
In The Pipeline
The cholesterol drug alirocumab, being developed jointly by Sanofi and Regeneron, has been piling up the positive study results of late. In October 2013, the partners announced that the Phase III ODYSSEY MONO trial of alirocumab met its primary efficacy endpoint. The mean low density lipoprotein-cholesterol (LDL-C, or “bad” cholesterol) reduction from baseline to week 24, the primary efficacy endpoint of the study, was significantly greater in patients randomized to alirocumab, as compared to patients randomized to ezetimibe (47.2 percent versus 15.6 percent). In the trial, which employed a dose increase (up-titration) for patients who did not achieve an LDL-C level of 70 milligrams/deciliter, the majority of patients remained on the initial low dose of alirocumab of 75 milligrams.
“We are excited with the findings from the first Phase III trial with alirocumab,” Dr. Edelberg says. “While the majority of our clinical program is investigating alirocumab in combination with lipid-lowering therapies, these monotherapy results are encouraging. We look forward to results from the remaining Phase III trials, which are investigating alirocumab in a variety of patient populations, combinations with different background therapies, and dosing regimens.”
Then, in July, the partners announced that nine new Phase III ODYSSEY trials of alirocumab in people with hypercholesterolemia met their primary efficacy endpoint of a greater percent reduction from baseline in low-density lipoprotein cholesterol (LDL-C) at 24 weeks compared to placebo or active comparator. In the nine ODYSSEY trials, the mean percent reduction in LDL-C from baseline at 24 weeks in alirocumab-treated patients was consistent with results seen in previous alirocumab trials.
“The robust data from these studies in more than 5,000 patients is the basis of our global regulatory submissions, which we expect in the U.S. and EU by year end,” Dr. Zerhouni says. “We look forward to potentially providing a new treatment option for patients who may need a more aggressive cholesterol-lowering treatment on top of standard of care.”
The following month, the partners announced detailed positive results from four Phase III ODYSSEY trials of alirocumab in people with hypercholesterolemia. Across the four trials, alirocumab showed significant and sustained reductions in LDL-C over one year on top of standard-of-care statin therapy across different patient types. Sanofi and Regeneron anticipate alirocumab regulatory submissions in the United States and EU by the end of 2014. In the United States, the companies intend to use a Priority Review Voucher to obtain priority review status for the alirocumab regulatory submission.
Also brewing in the Sanofi/Regeneron partnership pipeline is dupilumab, being developed for atopic dermatitis. In July, the two companies announced positive results from a Phase IIb dose-ranging study of dupilumab. In the trial, all five subcutaneous doses of dupilumab showed a dose-dependent improvement in the primary endpoint, the mean percent change in EASI score from baseline to week 16. The improvements in EASI score ranged from a high of 74 percent for patients in the highest dose group, who received 300 milligrams weekly, to a low of 45 percent in patients who received the lowest dose of 100 milligrams monthly, compared to 18 percent for patients in the placebo group. Dupilumab is also in development for asthma and nasal polyposis.
“Atopic dermatitis is known to have a profoundly negative effect on quality of life and people with more severe forms of this disease have limited therapeutic choices,” Dr. Zerhouni says. “These latest results are consistent with what was observed in the earlier clinical studies and add to the body of evidence that investigational dupilumab may have a role to play for patients with moderate-to-severe atopic dermatitis. We are now able to select the optimal doses for the Phase III studies, which we anticipate to begin later this year.”
A third product of the Sanofi/Regeneron partnership, the autoimmune compound sarilumab, is also getting closer to the market. Last November the partners announced that in the SARIL-RA-MOBILITY Phase III clinical trial in adult patients with active rheumatoid arthritis who were inadequate responders to methotrexate therapy, sarilumab treatment in combination with MTX improved disease signs and symptoms as well as physical function, and inhibited progression of joint damage. In June, new data from the same study showed that sarilumab increased major clinical response rates defined as achieving an ACR70 for at least 24 consecutive weeks and showed sustained improvement in signs and symptoms of RA after 52 weeks, which were secondary endpoints of the trial.
“Irreversible joint damage can be a consequence for patients suffering from rheumatoid arthritis, and this is accompanied by reduced physical function in these patients,” says Tanya M. Momtahen, Sarilumab Global Project head, Sanofi. “This remains a major concern for rheumatoid arthritis patients. We are encouraged by these Phase III results and the impact sarilumab demonstrated on inhibition of progression of structural damage assessed radiographically in this study.”
The Genzyme developmental multiple sclerosis drug Lemtrada, on the other hand, has had more of a roller-coaster ride lately. In September 2013, the European Commission approved Lemtrada for the treatment of adult patients with relapsing remitting multiple sclerosis with active disease defined by clinical or imaging features. In December, though, FDA sent Sanofi a Complete Response Letter regarding the company’s Lemtrada application. The agency took the position that Genzyme had not submitted evidence from adequate and well-controlled studies that demonstrated the benefits of Lemtrada outweigh its serious adverse effects. According to company leaders, that conclusion is related to the design of the completed Phase III active comparator studies of Lemtrada in relapsing-remitting MS patients. FDA has also taken the position that one or more additional active comparator clinical trials of different design and execution are needed prior to the approval of Lemtrada. In May, the agency accepted for review a resubmission of the Lemtrada application.
Aubagio, Sanofi and Genzyme’s other developmental MS compound, has enjoyed more success. In August 2013, the drug earned marketing authorization from the European Commission – it had been approved by FDA in September 2012. Then, in October 2013, the companies announced positive new data from the TOPIC study of once-daily, oral Aubagio showing that the drug had significantly reduced the risk of a new clinical relapse or MRI lesion over the two-year study period. Aubagio generated €166 million ($220 million) in sales for Sanofi in 2013, mostly in the United States. In the first half of 2014, the product generated another €175 million ($232 million).
In December, Sanofi announced the results of a 24-week Phase IIIb clinical study showing that Lyxumia met the primary endpoint of non-inferiority in blood sugar lowering (HbA1c) when administered either before breakfast or the main meal of the day. These results indicate that Lyxumia can effectively lower blood sugar at either time of administration. Lyxumia is already approved in Europe for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medicinal products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control. Sanofi plans to resubmit the NDA for Lyxumia with FDA in 2015, after completion of the ELIXA cardiovascular outcomes study.
Also in December, Sanofi announced the full results from the EDITION II study showing that investigational new insulin U300 demonstrated similar blood sugar control with 23 percent fewer patients experiencing night-time low blood sugar compared with Lantus. EDITION II met its primary endpoint by showing similar reductions in HbA1c from baseline between U300 and Lantus at six months in people with type 2 diabetes who had challenging baseline characteristics.
“We are encouraged by these results which suggest that U300 could be a viable treatment option for a wide range of people with type 1 and type 2 diabetes,” Mr. Chancel says.
In June, Sanofi announced that in a pooled analysis, the investigational therapy Toujeo consistently showed significantly fewer low blood sugar events (hypoglycemia) at any time of day, including night-time events, compared with Lantus. The pooled analysis comprised data from three differing type 2 patient populations. In this analysis, more pronounced, significant reductions in low blood sugar rates at any time of day, including nighttime, were observed with Toujeo during the 8-week titration period when compared with Lantus. Marketing applications for Toujeo were accepted by EMA in May and FDA in July.
In August 2014, FDA approved Cerdelga capsule, the only first-line oral therapy for certain adult Gaucher disease type 1 patients. The Cerdelga clinical development program was the largest ever conducted in Gaucher disease, with about 400 patients treated in 29 countries. The FDA approval was based on efficacy data from two positive Phase III studies for Cerdelga, one in patients new to therapy, and the other in patients switching from approved enzyme replacement therapies. The filing also incorporated four years of efficacy data from the Cerdelga Phase II study.
“More than 20 years ago, Genzyme introduced the world’s first treatment for Gaucher disease,” Dr. Meeker says. “We are proud to build on this legacy and continue to improve Gaucher patients’ lives through ongoing research and new therapies. The approval of Cerdelga represents our unwavering commitment to the Gaucher patient community.”
In August 2013, Sanofi Pasteur initiated a Phase III clinical program called Cdiffense to evaluate the safety, immunogenicity, and efficacy of an investigational vaccine for the prevention of primary symptomatic Clostridium difficile infection (CDI). C. difficile (C. diff) is a potentially life-threatening, spore-forming bacterium that causes intestinal disease. The risk of C. diff increases with age, antibiotic treatment, and time spent in hospitals or nursing homes, where multiple cases can lead to outbreaks. The investigational vaccine is designed to help protect at-risk individuals from C. diff, which is emerging as a leading cause of life-threatening, healthcare-associated infections worldwide.
“With the emergence of difficult-to-manage strains of C. diff, CDI has become more frequent, more severe and more difficult to treat in recent years, raising concerns about how to control it and prevent transmission”, says John Shiver, Ph.D., senior VP for Research & Development at Sanofi Pasteur. “Vaccination could be an efficacious, cost-effective and important public-health measure to protect individuals from C. diff.”
In April 2014, Sanofi Pasteur reported more good news about one of its developmental vaccines, this one for dengue disease. The company announced that the first of two pivotal Phase III efficacy studies with its dengue vaccine candidate had achieved its primary clinical endpoint. The efficacy study showed a significant reduction of 56 percent of dengue disease cases. Sanofi Pasteur’s dengue vaccine is the first ever to complete a Phase III efficacy study.
Then, in September 2014, the company announced that the final landmark Phase III efficacy study of its dengue vaccine candidate in Latin America successfully achieved its primary clinical endpoint. Results showed an overall significant reduction of 60.8 percent of dengue disease cases in children and adolescents 9 to 16 years old after a three-dose vaccination schedule. Importantly, efficacy was observed against each of the four dengue serotypes.
Additional observations of the results showed a clinically important reduction by 80.3 percent in the risk of hospitalization due to dengue during the study. The results also showed in the study population an efficacy against dengue hemorrhagic fever, the severe form of dengue, which is consistent with the results released from Sanofi’s Phase III dengue study in Asia. The results suggest better protection in case of prior exposure to dengue.
“For the first time ever, after 20 years of research and industrial commitment, dengue is set to become a vaccine preventable disease,” says Olivier Charmeil, president and CEO, Sanofi Pasteur. “The data generated from our comprehensive research and clinical program involving 40,000 children, adolescents, and adults from 15 countries, will be submitted to the health authorities in countries where dengue is a public health priority.”
