Although the market-exclusivity loss of Singulair has hurt the company’s top line of late, Merck has plenty of high-potential products on the market and in the pipeline with which to recover.
By Joshua Slatko firstname.lastname@example.org
As one of the world’s largest pharmaceutical companies, Merck has more than enough wherewithal to take a few punches and come back strong. The punches have been coming in flurries of late, with patent expirations for former sales leader Singulair as well as Cozaar and Hyzaar, plus the market withdrawal of Tredaptive and application withdrawal of ridaforolimus. But Merck has plenty of power left, led by the impressively successful diabetes product Januvia, the rapidly growing Zostavax and Victrelis, and several more high-potential compounds in the pipeline. Though the short-term effects of Singulair’s market-exclusivity loss supressed the company’s revenue in 2012 and will continue to do so during 2013, Merck’s leaderss are confident that their long-term vision will be vindicated.
“Ours is a business that requires a long-term focus, and Merck people have an unwavering commitment to our mission to save and improve lives around the world,” says Kenneth C. Frazier, chairman, president, and CEO of Merck. “We steadfastly believe that innovative research and development is the only sustainable way to create true and enduring value for customers, patients, and shareholders. By continuing to invest in the discovery and development of medicines and vaccines – though it is challenging and expensive – we believe Merck can have a profound impact on people’s lives for years to come.”
Merck’s top-line revenue in 2012 totaled $47.27 billion, a decrease of 1.6 percent compared with the previous year. Excluding the effects of Singular’s patent-protection loss, company executives project that Merck’s top line would have risen by 5 percent for the year. Net income dropped 1.7 percent to $6.17 billion, and earnings per share were down two cents to an even $2.00. In the first half of 2013 the company’s top line fell 9.8 percent to $21.68 billion, with income down 29.2 percent to $2.5 billion and EPS dropping 33 cents to $0.82. Company leaders are projecting full-year EPS for 2013 at between $1.84 and $2.05.
In its latest of a long list of impressive financial accomplishments, the diabetes product Januvia took over as Merck's best-seller in 2012, earning $4.09 billion in sales, a 22.9 percent improvement over the previous year. Including sales of the metformin-combination sister product Janumet, the Januvia family totaled $5.75 billion in sales for 2012, a 26.7 percent increase.
According to company leaders, this impressive performance reflected volume growth in the United States as well as in international markets, particularly in Japan. Sales of Januvia in the first half of 2013 totaled $1.96 billion, a 1.1 percent decrease compared with the first half of 2012; combined sales of Januvia and Janumet were $2.84 billion, an increase of 2.2 percent compared to the 2012 corresponding period.
Merck's previous top seller, the asthma and allergy product Singulair, lost its U.S. patent protection in August 2012; thus sales fell 29.7 percent for the year to $3.85 billion. In the first half of 2013, Singular sales tumbled to $618 million, a drop of 77.7 percent.
Sales of the cholesterol absorbtion inhibitor Zetia grew 5.7 percent to $2.57 billion in 2012, helped by a positive performance in the United States due to pricing, as well as volume growth in Japan, and partially offset by volume declines in the United States. The Zetia-Zocor combination product Vytorin generated $1.75 billion in 2012 sales, a decrease of 7.2 percent. In the first half of 2013, both of these trends continued; Zetia sales rose 2.6 percent to $1.28 billion, while Vytorin sales dropped 8.9 percent to $810 million.
Due to the loss of sales in markets relinquished to Johnson & Johnson in an arbitration settlement agreement in 2011, sales of the autoimmune drug Remicade fell 22.2 percent in 2012 to $2.08 billion. In the markets retained by Merck, Remicade sales declined 2 percent. In the first half of 2013, Remicade sales rose 3.7 percent to $1.08 billion, while sales of the Remicade follow-on Simponi were up 52 percent to $228 million.
Gardasil, Merck's HPV vaccine, enjoyed a nice sales bounce in 2012, rising 34.9 percent to $1.63 billion. This growth, company leaders say, was driven primarily by growth in the United States, reflecting continued uptake in males and about $45 million of government purchases for the U.S. Centers for Disease Control and Prevention Pediatric Vaccine Stockpile, as well as growth in the emerging markets – particularly in Latin America and the Asia Pacific region – and in Japan. In May, Merck was awarded a significant portion of the UNICEF human papillomavirus vaccine tender, and will provide sustained supply of Gardasil to GAVI-eligible countries. This agreement followed the GAVI Alliance’s earlier announcement that HPV vaccines would be included in its portfolio for the first time. GAVI (the Global Alliance for Vaccines and Immunization) is expected to support the introduction of HPV vaccination in 28 countries by the end of 2017. In the first half of 2013, Gardasil sales advanced 27.1 percent to $773 million versus the January-June 2012 result.
Sales of the HIV drug Isentress grew 11.5 percent in 2012 to $1.52 billion driven primarily by volume growth in the United States, Latin America, and the Asia Pacific region. In July, FDA approved new labeling for Isentress. The updated prescribing information now includes 240-week results from the STARTMRK study, the longest double-blind Phase III non-inferiority study evaluating an integrase inhibitor in treatment-naïve adult patients with HIV-1 infection. The results show that the regimen containing Isentress in combination therapy demonstrated long-term viral suppression and a greater immunologic response than the efavirenz-containing regimen, as well as a proven, long-term safety and tolerability profile through 240 weeks in previously untreated (treatment-naïve) adult HIV-1 infected patients. In the first half of 2013, Isentress sales rose 5.4 percent to $775 million.
The shingles vaccine Zostavax performed impressively for Merck in 2012, with sales nearly doubling from $332 million to $651 million. This improvement, company leaders say, came in part due to a resolution of difficulties Merck had been having for several years in producing its varicella zoster virus-containing vaccines; these difficulties suppressed sales performance in 2010 and 2011. Zostavax’s performance in 2012 reflected supply availability and increased promotional efforts in the United States. Merck anticipates limited launches outside of the United States later in 2013.
The most impressive sales jump by percentage in Merck's portfolio in 2012 came from the hepatitis C drug Victrelis, with the product's sales more than tripling from $140 million to $502 million in its first full year on the market. According to company leaders, this performance was driven by by post-launch growth in the United States and internationally, particularly in Europe.
Sales of Victrelis have dropped off of late, though; in the first half of 2013, the product generated $226 million in sales, a decrease of 5 percent. Victrelis is approved in 70 countries and has launched in at least 45 of those markets.
Partnerships and acquisitions
In July 2012, Merck announced two licensing agreements for investigational HIV drug candidates. The company signed a deal with Chimerix for CMX157, an investigational oral nucleoside reverse transcriptase inhibitor in Phase I clinical development. Under the agreement, Merck will receive an exclusive worldwide license and is responsible for development and commercialization of CMX157.
Merck signed an agreement with Yamasa Corp. to develop EFdA, a novel nucleoside reverse transcriptase inhibitor candidate that is in preclinical studies and has shown antiviral activity toward highly resistant HIV strains. As part of the agreement, Merck will pay an upfront fee and future milestones in return for exclusive worldwide license rights. This candidate was discovered in collaboration with a group led by the world renowned HIV research scientist Dr. Hiroaki Mitsuya of Kumamoto University’s Center for AIDS Research in Japan.
“Despite the tremendous advances made over the past 20 years, there remains considerable unmet need in the treatment of HIV infection,” says Robin D. Isaacs, M.D., VP, infectious disease clinical research, Merck Research Laboratories. “Merck remains committed to improving on the standard of care for HIV therapy.”
In October 2012, Merck and AiCuris entered into an exclusive worldwide licensing agreement for AiCuris’ novel portfolio of investigational medicines targeting human cytomegalovirus, including letermovir. The oral, late-stage antiviral candidate is being investigated for the treatment and prevention of HCMV infection in transplant recipients. Under the agreement, Merck, through a subsidiary, will gain worldwide rights to develop and commercialize candidates in AiCuris’ HCMV portfolio. AiCuris will receive a €110 million ($141.4 million) upfront payment and is eligible for milestone payments of up to €332.5 million ($427.6 million) based on successful achievement of development, regulatory and commercialization goals for HCMV candidates, including letermovir, an additional back-up candidate, and other Phase I candidates designed to act via an alternate mechanism. In addition, AiCuris will be entitled to receive royalty payments reflecting the advanced stage of the clinical program on any potential products that result from the agreement. Merck is responsible for all development activities and costs.
“There is a significant need for additional medicines for the treatment of HCMV infection, which is one of the most common viral infections affecting organ and bone marrow transplant patients,” says Dr. Roger Pomerantz, senior VP, Worldwide Licensing and Knowledge Management, and Infectious Disease Franchise Head, Merck Research Laboratories. “AiCuris has built a leading portfolio of innovative antiviral HCMV candidates that are designed to address novel targets and offer the potential for HCMV prophylaxis. This portfolio complements Merck’s broad antiviral portfolio.”
In November 2012, Merck and the Regenstrief Institute signed a five-year agreement to collaborate on a range of projects that will use clinical data to inform personalized delivery of healthcare. Regenstrief is a medical research organization closely associated with the Indiana University School of Medicine. The work will explore novel methods for studying diseases and interventions for chronic conditions such as diabetes, cardiovascular disease, and osteoporosis. The Regenstrief-Merck collaboration, company leaders say, seeks to improve the health of patients through data analytics, healthcare innovation, education, and research that supports evidence-based healthcare.
“This type of novel academic-industry collaboration can advance our understanding of a number of critical therapeutic areas, enabling novel use of health information technology to enhance drug development, medication safety and the personalization of therapeutics,” says Sachin H. Jain, M.D., chief medical information and innovation officer at Merck.
In December, Merck and GE Healthcare announced a clinical study collaboration, license, and supply agreement for use of [18F]Flutemetamol, an investigational positron emission tomography imaging agent, to support Merck’s development of MK-8931, a novel oral beta amyloid precursor protein site cleaving enzyme inhibitor and Merck’s lead investigational candidate for Alzheimer’s disease. Under the terms of the agreement, GE Healthcare will supply [18F]Flutemetamol to help select patients for clinical trials and evaluate this investigational agent as a companion diagnostic tool. A joint Merck and GE Healthcare Imaging Advisory Committee will oversee the planned imaging studies.
“There is a serious unmet need for a reliable method for measuring beta amyloid deposits to help physicians diagnose Alzheimer’s disease at its different stages and study its progression,” says Darryle Schoepp, Ph.D., senior VP, head of neuroscience and ophthalmology, Merck Research Laboratories. “This agreement will allow us to employ an investigational imaging agent to help identify patients who might benefit from an anti-amyloid therapy and enable clinical evaluation of our lead BACE inhibitor candidate for Alzheimer’s disease, MK-8931.”
During February 2013, Merck and Samsung Bioepis entered into an agreement to develop and commercialize multiple pre-specified and undisclosed biosimilar candidates. Under the agreement, Samsung Bioepis is responsible for preclinical and clinical development, process development and manufacturing, clinical trials, and registration. Merck is responsible for commercialization. Samsung Bioepis will receive an upfront payment from Merck, product supply income, and is eligible for additional payments associated with pre-specified clinical and regulatory milestones. Samsung Bioepis, which is a joint venture between Samsung Biologics and Biogen Idec, aims to develop affordable and high-quality biopharmaceutical and biosimilar products.
“The combination of Merck’s global commercial presence with Samsung Bioepis’ biologic development and manufacturing capabilities positions the two companies well to increase access to biosimilars to improve human health,” says Rich Murray, Ph.D., senior VP, biologics and vaccines research, Merck Research Laboratories. “We look forward to this collaboration and its potential to complement our expanding internal biologics portfolio.”
In March, Merck and Luminex signed a collaboration and license agreement to develop a companion diagnostic device that will be evaluated to help screen patients for recruitment into Merck’s clinical development program for MK-8931. Luminex is responsible for development, regulatory submission, and commercialization of the candidate companion diagnostic device, which will employ Luminex’s xMAP Technology to measure concentrations of two candidate biomarkers (AB42 and t-tau) in cerebrospinal fluid samples from patients with mild cognitive impairment. The candidate device will be evaluated as a means to identify subjects with MCI who have a higher risk of developing AD to support patient selection for Merck’s therapeutic BACE inhibitor clinical program.
“Evaluation of biomarkers that may provide an indicator of disease onset and enable earlier diagnosis is an important goal toward facilitating early intervention and potentially improving the treatment of Alzheimer’s disease,” Dr. Schoepp says. “We look forward to working with Luminex to advance our ongoing clinical development program for MK-8931.”
In April, Merck entered into a non-exclusive agreement with Bristol-Myers Squibb to conduct a Phase II clinical trial. The study is evaluating the safety and efficacy of a once-daily oral combination regimen consisting of Bristol-Myers Squibb’s investigational NS5A replication complex inhibitor daclatasvir and Merck’s investigational NS3/4A protease inhibitor MK-5172 for the treatment of chronic hepatitis C virus infection, genotype 1. The planned initiation of the Phase II clinical trial follows the completion of a Phase I safety evaluation of the investigational combination regimen. Under the agreement, Merck is conducting the Phase II clinical trial. Further clinical development activities beyond the Phase II study are not covered as part of this agreement.
“In HCV, agreements like this that combine novel investigational candidates are important to evaluate the potential of novel oral regimens early in the development cycle,” says Eliav Barr M.D., VP, Infectious Diseases, Project Leadership and Management, Merck Research Laboratories. “We are pleased to collaborate with Bristol-Myers Squibb to advance this potential all-oral combination.”
Also in April, Merck and Pfizer entered into a worldwide (except Japan) collaboration agreement for the development and commercialization of Pfizer’s ertugliflozin, an investigational oral sodium glucose cotransporter inhibitor being evaluated for the treatment of type 2 diabetes. Ertugliflozin is Phase III ready, with trials expected to begin later in 2013. Under the terms of the agreement, Merck, through a subsidiary, and Pfizer will collaborate on the clinical development and commercialization of ertugliflozin and ertugliflozin-containing fixed-dose combinations with metformin and Januvia tablets. Merck continues to retain the rights to its existing portfolio of sitagliptin-containing products. Pfizer has received an upfront payment and milestones of $60 million and will be eligible for additional payments associated with the achievement of pre-specified future clinical, regulatory and commercial milestones. Merck and Pfizer will share potential revenues and certain costs on a 60/40 percent basis.
“Merck continues to build upon our leadership position in the oral treatment of type 2 diabetes through our own research and business development,” says Nancy Thornberry, senior VP and Diabetes and Endocrinology franchise head, Merck Research Laboratories. “We believe ertugliflozin has the potential to complement our strong portfolio of investigational and marketed products, and we look forward to collaborating with Pfizer on its development.”
In September, Merck and AstraZeneca announced a worldwide licensing agreement for MK-1775, Merck’s oral small molecule inhibitor of WEE1 kinase. MK-1775 is being evaluated in Phase IIa clinical studies in combination with standard-of-care therapies for the treatment of patients with certain types of ovarian cancer. Under the terms of the agreement, AstraZeneca will pay Merck a $50 million upfront fee. In addition Merck will be eligible to receive future payments tied to development and regulatory milestones, plus sales-related payments and tiered royalties. AstraZeneca is responsible for all future clinical development, manufacturing, and marketing.
“Merck is committed to advancing potentially meaningful therapeutic options promptly for patients with cancer,” says Iain D. Dukes, senior VP and head of licensing and external scientific affairs, Merck. “We are pleased to enter this agreement with AstraZeneca to realize the potential of MK-1775 while we focus on advancing our later stage oncology programs, MK-3475 and vintafolide.”
Also in September, Merck and Maccabi Healthcare Services, a 2 million member healthcare provider in Israel, launched a multi-year agreement to use real-world data from Maccabi’s longitudinal database to inform novel, patient-centered health approaches. Maccabi and Merck will apply technical and information research capabilities to draw insights from Maccabi’s data to support personalized healthcare delivery strategies across several therapeutic areas, including prevalent and costly chronic diseases. Specifically, the parties seek to enable better understanding of unmet patient needs, real-world outcomes achieved with medical treatments, and optimal approaches for improving patient adherence. A pioneer in electronic medical records, Maccabi has gathered and maintained an electronic medical record database since 1993, providing a valuable picture of longitudinal patient health that tracks how visits to primary care physicians, hospitals, and pharmacies, plus demographic shifts during the past 20 years, influence health outcomes.
“Market forces are demanding that all of us involved in healthcare find ways to enhance the quality of care while also offering greater efficiency and value, including research-driven companies like Merck,” Dr. Jain says. “In order to actually reduce costs and optimize quality, we’re going to need to have new breakthroughs – in medicines and vaccines, as well as how we structure and organize and deliver care to patients. By harnessing the power of large data sets such as Maccabi’s, we have an opportunity to derive new insights about diseases, treatment paradigms and patients – so we can work to address the most important medical needs of patients as well as the needs of payers.”
Research and development
In July 2012, the data monitoring committee for the Phase III trial assessing fracture risk reduction with odanacatib, Merck’s investigational cathepsin K (cat-K) inhibitor, completed its first planned interim analysis for efficacy and recommended that the study be closed early due to robust efficacy and a favorable benefit-risk profile. As a result, Merck began taking steps to close the trial. The DMC noted that safety issues remain in certain selected areas and made recommendations with respect to following up on them. Merck’s previously announced plan to conduct a blinded extension trial will allow further monitoring of the issues. The extension trial will also continue to measure efficacy.
In October 2012 Merck announced results from the PURSUE Phase III study of 1,390 women, aged 35-42 years, for corifollitropin alfa, the company’s investigational fertility treatment for controlled ovarian stimulation in women participating in vitro fertilization or intracytoplasmic sperm injection. The study met its primary endpoint of achieving vital pregnancy rates with data revealing that a single injection of 150 micrograms of corifollitropin alfa was non-inferior to seven daily injections of 300 IU recombinant follicle stimulating hormone. The study also evaluated key secondary endpoints of ongoing pregnancy rates and the number of oocytes (the female reproductive cell prior to fertilization) retrieved. An NDA for corifollitropin alfa was accepted for review by FDA in September. The compound is already approved in more than 50 markets outside the United States, including the European Union.
“Infertility is an issue faced by many couples in the United States,” says Barbara Stegmann, M.D., reproductive endocrinology and infertility specialist, and principal scientist and clinical lead fertility, Merck. “The filing of corifollitropin alfa is an example of Merck’s commitment to patients and scientific innovation. We thank the patients and physicians who have participated in the clinical trials that are so essential to developing innovative fertility treatment options.”
Also in October, Merck published Phase IIb data for MK-3102, the company’s investigational once-weekly DPP-4 inhibitor in development for the treatment of type 2 diabetes. MK-3102 significantly lowered blood sugar in this 12-week study compared with placebo, with an incidence of symptomatic hypoglycemia that was similar to placebo, in patients with type 2 diabetes. Phase III trials of the compound are already under way.
“Since the discovery of the DPP-4 inhibitor class, Merck has been actively committed to advancing the science of how to treat type 2 diabetes,” Ms. Thornberry notes. “We are encouraged by these Phase IIb results in patients with type 2 diabetes, and we are initiating Phase III studies to move MK-3102 forward in the development process.”
In November, Merck formally notified the European Medicines Agency that the company was withdrawing the marketing authorization application for ridaforolimus, an investigational small-molecule inhibitor of the mTOR protein. mTOR acts as a central regulator of protein synthesis, cell proliferation, cell cycle progression and cell survival, integrating signals from proteins such as PI3K, AKT and PTEN known to be important to malignancy. The application for ridaforolimus had been accepted by the EMA in August 2011. At the time of the withdrawal it was under review by the regulatory agency’s Committee for Medicinal Products for Human Use. In its letter to the EMA, Merck said the withdrawal of ridaforolimus was based on the provisional view of the CHMP that the data available to date and provided in the MAA were not sufficient to permit licensure of ridaforolimus in the European Union for the maintenance treatment of patients with soft tissue sarcoma or primary malignant bone tumor. Although the application for these uses was withdrawn, Merck is studying ridaforolimus in combination with other drugs in other tumor types.
Also in November, the European Commission accepted for review the marketing authorization application from Merck and partner developer Endocyte for the novel investigational cancer candidate vintafolide and the investigational companion diagnostic imaging agent etarfolatide, for the targeted treatment of patients with folate-receptor positive platinum-resistant ovarian cancer in combination with pegylated liposomal doxorubicin. Both vintafolide and etarfolatide have been granted orphan drug status by the European Commission.
Vintafolide is a proprietary, injectable, conjugate consisting of folate (vitamin B9) linked to a potent vinca alkaloid anticancer agent, desacetylvinblastine hydrazide (DAVLBH). Folate is essential for cell division, and cancer cells generally consume higher levels of folate than normal cells to fuel their rapid rate of growth and division. In order to satisfy the demand for folate, some cancer cell types – including ovarian – express high concentrations of folate receptors on their surface. Vintafolide is designed to exploit this characteristic by selectively targeting the folate receptor to deliver the anticancer agent DAVLBH intracellularly to the tumor. The compound is being evaluated in a Phase III randomized, double-blind clinical trial for platinum-resistant ovarian cancer.
In December 2013, Merck announced that the HPS2-THRIVE study of MK-0524A/Tredaptive did not meet its primary endpoint. In the study, adding the combination of extended-release niacin and laropiprant to statin therapy did not significantly further reduce the risk of the combination of coronary deaths, non-fatal heart attacks, strokes, or revascularizations compared to statin therapy. In addition, there was a statistically significant increase in the incidence of some types of non-fatal serious adverse events in the group that received extended-release niacin/laropiprant compared to statin therapy. Merck does not plan to seek regulatory approval for the medicine in the United States. In January 2013, based on the understanding of the preliminary data from the HPS2-THRIVE study and in consultation with regulatory authorities, the company began taking steps to suspend the availability of Tredaptive, which had been approved for use in certain countries outside of the United States.
Additionally during December, Merck launched a Phase II/III clinical trial designed to evaluate the safety and efficacy of MK-8931 versus placebo in patients with mild-to-moderate Alzheimer’s disease. The novel investigational oral B-amyloid precursor protein site-cleaving enzyme inhibitor MK-8931 is the first with this mechanism to advance to this stage of clinical research. The global, multi-center study called EPOCH is designed to initially evaluate the safety of MK-8931 in a cohort of 200 patients prior to advancing into a larger Phase III study.
“Merck is committed to advancing the understanding and treatment of Alzheimer’s disease,” Dr. Schoepp says. “As the global health and financial burden of Alzheimer’s disease grows, innovative research is critically needed, and we need to accelerate this research wherever possible. This new study is an important step in our overall strategy to understand the potential of the BACE inhibitor mechanism and MK-8931, our lead compound, in multiple stages of Alzheimer’s disease.”
In March 2013, FDA accepted for review Merck’s biologics license application for its investigational Timothy grass pollen (Phleum pratense) allergy immunotherapy tablet. The BLA for Merck’s grass pollen AIT was supported by Phase III trials that evaluated the safety and efficacy of the investigational product, including a long-term, multi-season trial. A BLA for Merck’s investigational ragweed pollen (Ambrosia artemisiifolia) sublingual allergy immunotherapy tablet was subsequently accepted for review by FDA in May.
“We are pleased to have achieved this important milestone in the development of our investigational grass pollen AIT, which, if approved, would represent a potential new option for allergy specialists to offer appropriate allergic rhinitis patients,” says Jeffrey A. Chodakewitz, M.D., senior VP, Global Scientific Strategy, franchise head, Infectious Diseases and interim franchise head, Respiratory & Immunology, Merck Research Laboratories.
In April, FDA designated lambrolizumab (MK-3475) as a Breakthrough Therapy for the treatment of patients with advanced melanoma. Lambrolizumab is Merck’s investigational antibody therapy targeting programmed death receptor (PD-1) that is currently being evaluated for the treatment of patients with advanced melanoma, and other tumor types.
“We are pleased that the FDA has designated lambrolizumab a Breakthrough Therapy for patients with advanced melanoma,” said Gary Gilliland M.D., Ph.D., senior VP and oncology franchise head, Merck Research Laboratories. “The FDA’s decision to place lambrolizumab in a category that may enable expedited development and review is an important milestone for Merck as we advance ongoing programs in multiple cancer indications.”
During May 2013, FDA approved Merck’s Liptruzet tablets for the treatment of elevated low-density-lipoprotein cholesterol in patients with primary or mixed hyperlipidemia as adjunctive therapy to diet when diet alone is not enough. Liptruzet contains Zetia, an efficacious LDL cholesterol lowering therapy, and Lipitor, one of the most widely prescribed statins in the United States. Once-daily Liptruzet treats two sources of cholesterol by inhibiting both the absorption of cholesterol in the digestive tract – through Zetia – and the production of cholesterol in the liver – through Lipitor.
Also in May, Merck announced that an initial review of data from three separate Phase III trials did not provide evidence of efficacy for preladenant, the company’s investigational adenosine A2A receptor antagonist for the treatment of Parkinson’s disease, compared with placebo. Based on these results, Merck is taking steps to discontinue the extension phases of these studies and no longer plans to pursue regulatory filings for preladenant.
In July 2013, Merck announced that the NDA for its investigational anti-thrombotic medicine vorapaxar had been accepted for standard review by FDA. Merck is seeking U.S. regulatory approval of vorapaxar for the secondary prevention of cardiovascular events in patients with a history of heart attack and no history of stroke or transient ischemic attack.
Also in July, Merck received a complete response letter from FDA for suvorexant, the company’s investigational medicine for the treatment of insomnia. In the letter, FDA advised Merck that the efficacy of suvorexant has been established at doses of 10 milligrams to 40 milligrams in elderly and non-elderly adult patients; that 10 milligrams should be the starting dose for most patients, and must be available before suvorexant can be approved; that 15-milligram and 20-milligram doses would be appropriate in patients in whom the 10-milligram dose is well-tolerated but not effective; and, for patients taking concomitant moderate CYP3A4 inhibitors, a 5-milligram dose would be necessary. In addition, FDA determined that the safety data do not support the approval of suvorexant 30 milligrams and 40 milligrams.
Based on initial review of the letter, Merck has determined that additional clinical studies of suvorexant 10 milligrams will not be necessary. However, manufacturing studies will be required to advance the 10-milligram dosage form. Merck will discuss with FDA whether additional studies will be required to support the 5-milligram dose.
A number of other Merck compounds are undergoing Phase III clinical development. These compounds include anacetrapib for atherosclerosis, actoxumab/bezlotoxumab for Clostridium difficile infection, vaniprevir for hepatitis C, V503 for HPV-related cancers, the investigational pediatric hexavalent combination vaccine V419, and tildrakizumab. The latter is an investigational therapeutic antibody that is designed to target Interleukin-23 (IL-23). Tildrakizumab is being evaluated for the treatment of psoriasis.
Product sales and financial performance
Product sales sales
Januvia $4,086 $3,324
Singulair $3,853 $5,479
Zetia $2,567 $2,428
Remicade $2,076 $2,667
Vytorin $1,747 $1,882
Janumet $1,659 $1,363
Gardasil $1,631 $1,209
Isentress $1,515 $1,359
Hyzaar $1,284 $1,663
M-M-R II,Varivax $1,273 $1,202
Nasonex $1,268 $1,286
Temodar $917 $935
Fosamax $676 $855
PegIntron $653 $657
Zostavax $651 $332
Maxalt $638 $639
NuvaRing $623 $623
Cancidas $619 $640
RotaTeq $601 $651
Pneumovax $580 $498
Victrelis $502 $140
All sales are in millions of dollars.
Revenue $47,267 $48,047
Net Income $6,168 $6,272
Diluted EPS $2.00 $2.02
R&D $8,168 $8,467
Revenue $21,681 $24,041
Net Income $2,499 $3,531
Diluted EPS $0.82 $1.15
R&D $4,008 $4,026
All figures are in millions of dollars except EPS.
Posted: October 2013