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MERCK & CO. 2014

Written by: | josh.slatko@medadnews.com | Dated: Wednesday, October 1st, 2014

One Merck Drive
Whitehouse Station, NJ 08889-0100
Telephone: 908-423-1000
Website: merck.com

Best-Selling Products

PRODUCT 2013 SALES 2012 SALES
Januvia $4,004 $4,086
Zetia $2,658 $2,567
Remicade $2,271 $2,076
Gardasil $1,831 $1,631
Janumet $1,829 $1,659
Isentress $1,643 $1,515
Vytorin $1,643 $1,747
Nasonex $1,335 $1,268
ProQuad/M-M-R II/ $1,306 $1,273
Varivax    
Singulair $1,196 $3,853
Cozaar/Hyzaar $1,006 $1,284
Zostavax $758 $651
Temodar $708 $917
NuvaRing $686 $623
Cancidas $660 $619
Pneumovax 23 $653 $580
Rotateq $636 $601
Fosamax $560 $676
Emend $507 $489
Simponi $500 $331

All sales are in millions of dollars.

Financial Performance

  2013 2012
Revenue $44,033 $47,267
Net income $4,517 $6,299
EPS $1.47 $2.00
R&D expense $7,503 $8,168
  1H14 1H13
Revenue $21,198 $21,681
Net income $3,764 $2,551
EPS $1.25 $0.82
R&D expense $3,238 $4,008

In millions of dollars, except EPS

Narrowing The Focus

The leaders of Merck have picked their priorities – immuno-oncology, Alzheimer’s, HCV, and externally sourced R&D – and are reshaping their company accordingly.

The Merck of today is looking decidedly more svelte than it looked a year ago. With the announcement of a major operations initiative last October, the company inaugurated a year of downsizing and narrowing R&D focus, in which some items – the company’s lead oncology immunotherapy, Alzheimer’s, and HCV and HPV programs – are clearly at the top of the priority list, and some others – Consumer Care, ophthalmics, APIs, a schizophrenia drug, and a healthy chunk of the in-house R&D staff – are not.

“In 2013 we took decisive action to sharpen our focus, reduce our cost structure and advance our innovative research and development,” says Kenneth C. Frazier, chairman and CEO of Merck. “This year we are excited about the potential of our near- and long-term pipeline, poised for long-term growth and committed to providing continued value to patients, customers and our shareholders.”

All this weight loss has thinned some of Merck’s other key numbers as well. In 2013 the company generated $44.03 billion in revenue, a decrease of 6.8 percent. Net revenue was down even more sharply, falling 28.3 percent to $4.52 billion, though this was impacted significantly by one-time acquisition and restructuring costs. R&D expense fell by 8.1 percent to $7.5 billion, and earnings per share were down 53 cents to $1.47. In the first half of 2014, Merck’s top line shed another 2.2 percent to $21.2 billion, but with most of the extraordinary expenses out of the way the bottom line rose 47.5 percent to $3.76 billion and EPS was up 43 cents to $1.25. R&D spending for the first half of the year was down 19.2 percent to $3.24 billion.

Operations Initiative

In October 2013 Merck announced a global initiative to sharpen its commercial and R&D focus. The multi-year initiative will enable Merck to better target its resources behind those opportunities that have the potential to deliver the greatest return on investment, including bolstering its pipeline and implementing a more agile operating model, with a significantly reduced, more flexible cost structure.

“These actions will make Merck a more competitive company, better positioned to drive innovation and to more effectively commercialize medicines and vaccines for the people who need them,” Mr. Frazier said on the announcement. “Today’s announcement further underscores that we are committed to improving our performance in the short term while also investing for the long term to create value for patients, customers and shareholders.”

Company leaders expect to realize about $2.5 billion in annual net cost savings by the end of 2015 and estimate that $1 billion, or 40 percent, of the savings will be realized by the end of 2014. The company anticipates that the substantial majority of savings will come from marketing and administrative expenses and R&D. These savings are off of the company’s full-year 2012 expense levels. By the end of 2015, the workforce reductions combined with previously announced reductions of about 7,500, were targeted to result in a decrease of about 20 percent in Merck’s total global workforce of 81,000 employees. Total pre-tax costs for the new restructuring program were estimated to range between $2.5 billion and $3 billion.

Within the core human pharmaceutical and vaccine business, Merck plans to continue to support its in-line portfolio and prepare for promising launches in the pipeline. The company will increase its focus on the key therapeutic areas that meet unmet medical needs, provide the best opportunities for the business and deliver the greatest value for customers – diabetes, acute hospital care, vaccines, and oncology.

Merck also announced the creation of a new, integrated unit to ensure that the company is prepared to successfully bring MK-3475, its investigational anti-PD-1 immunotherapy, to patients throughout the world.

Geographically, the company will increase its focus in 10 prioritized markets, which account for the majority of revenue in its pharmaceutical and vaccine business. These markets are the United States, Japan, France, Germany, Canada, the United Kingdom, China, Brazil, Russia, and Korea.

As a part of the initiative, Merck has prioritized its R&D efforts to focus on candidates capable of providing unambiguous, promotable advantages to patients and payers. This focus will include programs such as the company’s anti-PD-1 immunotherapy program in oncology, BACE for Alzheimer’s disease (MK-8931), the company’s next generation HCV program, and V503, Merck’s 9-valent HPV vaccine.

Merck will pursue emerging product opportunities independent of therapeutic area or modality and build its biologics capabilities. The company will out-license or discontinue selected late-stage clinical development assets and reduce its focus on platform technologies, and will make externally sourced programs a greater component of its pipeline strategy.

“While these actions are essential to ensure that Merck can continue to fulfill its mission into the future, they are nevertheless difficult decisions because they affect our dedicated and talented colleagues,” Mr. Frazier said. “We appreciate the contributions of all our employees, and we will support them during this time of transformation.”

In the days and months after the operations initiative announcement, Merck also announced several related divestitures. In October, the company sold its active pharmaceutical ingredient business in the Netherlands along with several products in its Diversified Brands portfolio to Aspen Holdings. The annual sales associated with the API business and products totalled about $430 million. In November, Merck sold the U.S. rights to three branded ophthalmic products — AzaSite, Cosopt, and Cosopt PF – to Akorn Inc. for $52.8 million; the three products had annual sales of about $43 million. And in December, Merck entered into an agreement to sell the U.S. rights to Saphris, a treatment for adult patients with schizophrenia or acute bipolar mania. Under the terms of the agreement, Forest Laboratories Inc. made an upfront payment of $240 million and agreed to make additional payments to Merck based on defined sales milestones. Saphris’ annual U.S. sales have been about $150 million.

Acquisitions And Partnerships

In September 2013, Merck and AstraZeneca announced a worldwide licensing agreement for Merck’s oral small molecule inhibitor of WEE1 kinase, MK-1775. 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. WEE1 helps to regulate the cell-division cycle. The WEE1 inhibitor MK-1775 is designed to cause certain tumor cells to divide without undergoing normal DNA repair processes, ultimately leading to cell death. Preclinical evidence suggests that the combination of MK-1775 and DNA damage-inducing chemotherapy agents can enhance anti-tumor properties, in comparison to chemotherapy alone.

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 health-care provider in Israel, launched a new multi-year collaboration to take advantage of 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 health-care 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.

“Market forces are demanding that all of us involved in health care find ways to enhance the quality of care while also offering greater efficiency and value, including research-driven companies like Merck,” says Sachin Jain, M.D., chief medical information and innovation officer, Merck. “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.”

In December, Merck announced the initiation of a clinical trial to evaluate the combination of the company’s investigational anti-PD-1 immunotherapy MK-3475 and GlaxoSmithKline’s orally administered kinase inhibitor pazopanib, in advanced renal cell carcinoma. Merck and GlaxoSmithKline entered a collaboration to study MK-3475 with pazopanib and other agents in the GlaxoSmithKline portfolio in the future. This Phase I/II clinical trial is designed to evaluate the safety and efficacy of a combination of MK-3475 and pazopanib in treatment-naïve patients with advanced renal cell carcinoma.

“Collaborations like this are central to Merck’s strategy to evaluate the potential of MK-3475 for the treatment of cancer,” Mr. Dukes says. “We look forward to initiating further collaborations to investigate MK-3475 in combination with other anti-cancer agents across a range of tumor types.”

Expanding on this very point, in February, Merck signed separate clinical collaboration agreements with Amgen Inc., Incyte Corp., and Pfizer Inc. to evaluate novel combination regimens with MK-3475. Pfizer and Merck will evaluate in Phase I/II clinical studies the safety and efficacy of MK-3475 in combination with Pfizer’s small molecule kinase inhibitor Inlyta in patients with renal cell carcinoma, and separately MK-3475 plus PF-05082566, an investigational immuno-oncology agent that targets the human 4-1BB receptor, in multiple cancer types. Incyte and Merck will collaborate on a randomized, double-blind placebo-controlled Phase I/II study to evaluate the safety and efficacy of a regimen combining MK-3475 with Incyte’s investigational immunotherapy agent INCB24360, an indoleamine 2, 3-dioxygenase inhibitor, in patients with previously treated metastatic and recurrent NSCLC, among other advanced or metastatic cancers. Amgen and Merck will evaluate MK-3475 in combination with Amgen’s investigational oncolytic immunotherapy talimogenelaherparepvec in a Phase I/II study in patients with previously untreated advanced melanoma.

“Merck clinical scientists intend to explore the potential of our PD-1 inhibitor across a wide range of cancers, both as monotherapy and in combination,” says Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “These new collaborations with Amgen, Incyte, and Pfizer underscore our shared determination to evaluate treatment regimens with the potential to provide meaningful benefits to patients suffering from cancer.”

Also in February, Merck and Samsung Bioepis Co. expanded their collaboration with an agreement to develop, manufacture, and commercialize MK-1293, an insulin glargine candidate for the treatment of patients with type 1 and type 2 diabetes. Phase III clinical studies in type 1 and type 2 diabetes were expected to begin soon. Under the terms of the agreement, the companies will collaborate on clinical development, regulatory filings and manufacturing. If approved, Merck will commercialize this candidate. This collaboration builds on the agreement made by the two companies in February 2013 to develop and commercialize multiple biosimilar candidates.

“We look forward to collaborating with Samsung Bioepis on this insulin glargine candidate, as diabetes is a top priority for the company,” says Matt Strasburger, senior VP, Diabetes, Global Human Health, Merck. “Merck is strengthening its leadership in diabetes through our own work and in collaboration with others, and this agreement will help build our portfolio across the spectrum of the disease.”

In May, Merck entered into an agreement to sell its Merck Consumer Care business to Bayer AG for $14.2 billion. Under the terms of the agreement, Bayer acquires Merck’s existing OTC business, including the global trademark and prescription rights for Claritin and Afrin. The company also announced a worldwide clinical development collaboration with Bayer to market and develop its portfolio of soluble guanylatecyclase modulators. This includes Bayer’s Adempas, the first member of this novel class of compounds. Adempas is approved to treat pulmonary arterial hypertension and is the first drug treatment approved for patients with chronic thromboembolic pulmonary hypertension. The two companies will equally share costs and profits from the collaboration and implement a joint development and commercialization strategy.

“The sale of our consumer care business is part of our efforts to ensure that assets within our portfolio align with our core strategy, have industry-leading potential and generate long-term shareholder value,” Mr. Frazier says. “By unlocking value in Merck Consumer Care, we’re able to further our goal of being the premier research-intensive biopharmaceutical company through targeted investments that strengthen our product portfolio and enhance our pipeline.”

The collaboration also includes clinical development of vericiguat, which is in Phase II trials for worsening heart failure, as well as opt-in rights for other early-stage sGC compounds in development at Bayer. Merck will in turn make available its early-stage sGC compounds under similar terms.

In return for these broad collaboration rights, Bayer will receive a $1 billion up-front payment with the potential for additional milestone payments upon the achievement of agreed-upon sales goals. For Adempas, Bayer will continue to lead commercialization in the Americas, while Merck will lead commercialization in the rest of the world. For vericiguat and other potential opt-in products, Bayer will lead in the ROW and Merck will lead in the Americas. For all products and candidates included in the agreement, both companies will share in development costs and profits on sales and will have the right to copromote in territories where they are not the lead.

In August, Merck entered into an agreement to explore the therapeutic potential of the combination of Pfizer’s Xalkori with MK-3475 – now named Keytruda (pembrolizumab) – in a Phase Ib clinical study evaluating the safety and tolerability of the combination in patients with ALK-positive advanced or metastatic non-small cell lung cancer. This multi-center, open-label clinical study is expected to begin in 2015. Pfizer will conduct the study.

“We are pleased to build upon our ongoing collaboration with Pfizer to evaluate potential combination regimens incorporating Merck’s investigational immunotherapy pembrolizumab,” said Dr. Eric Rubin, VP, Oncology, Merck Research Laboratories. “Evidence from early studies of pembrolizumabmonotherapy together with Xalkori’s proven targeted therapeutic approach provides the scientific rationale for evaluating this combination for the treatment of lung cancer.”

Product Performance

After several consecutive years of impressive growth, the performance of Merck’s leading product, the diabetes drug Januvia, finally slowed down in 2013, with sales dropping by 2 percent to $4 billion. Company leaders blamed this slowdown on the unfavorable effects of foreign exchange and decreasing demand in the United States. In the first half of 2014, Januvia sales edged downward again, falling another 2 percent to $1.92 billion. Sales of Januvia’s sister product Janumet, a combination of Januvia with metformin, have continued to grow; Janumet sales rose 10.2 percent in 2013 to $1.83 billion and 12.7 percent in the first half of 2014 to $995 million, driven primarily by volume growth outside the United States.

Sales of another pair of sister products – the cholesterol drugs Zetia and Vytorin – remained largely static for Merck in 2013, with Zetia sales up 3.5 percent to $2.66 billion and Vytorin sales dropping 6 percent to $1.64 billion; the two products’ combined sales decreased by 0.3 percent for the year. The story has been essentially the same in the first half of 2014; Zetia sales rose 3.8 percent to $1.33 billion while Vytorin sales fell 4.1 percent to $777 million, with a net positive change for the pair of 0.8 percent. Vytorin is a combination of Zetia with the statin Zocor.

The autoimmune product Remicade enjoyed 9.4 percent growth in 2013 in Merck’s markets, with sales up to $2.27 billion – the company is responsible for Remicade in Europe, Russia, and Turkey. But Merck’s Remicade run is coming to an end soon; in September 2013, the European Commission approved an infliximab biosimilar. While the company is experiencing generic competition in certain smaller European markets, Merck leaders anticipate a more substantial decline in Remicade sales following loss of market exclusivity in major European markets in February 2015. In the first half of 2014, Remicade sales for Merck rose 12.5 percent to $1.21 billion.

Remicade’s follow-on product, Simponi, is showing signs of inheriting its predecessor’s place at the top of Merck’s autoimmune portfolio. Simponi sales rose by an impressive 51.1 percent in 2013 to an even $500 million, and sales were up another 44.7 percent in the first half of 2014 to $330 million. In September 2013, the European Commission approved Simponi for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy or who are intolerant to or have medical contraindications for such therapies.

Gardasil, Merck’s vaccine for HPV, grew its sales by 12.3 percent in 2013 to $1.83 billion, driven primarily by volume growth in the United States and Latin America. This performance was particularly impressive given that the Japanese Health Ministry suspended all active promotion of HPV vaccines in June 2013, which meant that the vaccine recorded barely any sales at all in Japan in the second half of the year. In the first half of 2014, Gardasil sales rose 2.5 percent to $792 million.

Merck’s leading HIV product Isentress has been in the news frequently over the past year and more. Last July FDA approved new labeling for the drug, including 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.

Then, in January 2014, FDA approved Isentress for pediatric use, expanding the drug’s indication to include patients 4 weeks of age and older. And in June, Merck announced that the first patient had been enrolled in the company’s global Phase III clinical trial, ONCEMRK, assessing a once-daily investigational formulation of Isentress as part of combination HIV therapy for treatment-naïve HIV-1-infected adults. Isentress film-coated tablets are currently administered twice daily. Alongside all these new developments, Isentress’ sales have improved too, rising 8.4 percent to $1.64 billion in 2013 and 8.8 percent to $843 million in the first half of 2014.

In The Pipeline

The top of Merck’s pipeline has been particularly busy in recent months, with a number of prominent new compound approvals. In April, FDA approved Grastek. The newly approved product is an allergen extract indicated as immunotherapy for the treatment of grass pollen-induced allergic rhinitis with or without conjunctivitis confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies for timothy grass or cross-reactive grass pollens. A few days after the approval of Grastek, FDA also approved Ragwitek, an allergen extract indicated as immunotherapy for the treatment of short ragweed pollen-induced allergic rhinitis with or without conjunctivitis confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies for short ragweed pollen.

“The FDA approval of Grastek brings an important new sublingual tablet for allergy specialists treating adults and children with allergic rhinitis with or without conjunctivitis caused by timothy or cross-reactive grass pollens,” says Dr. Sean Curtis, VP, Respiratory and Immunology, Merck Research Laboratories. “This important milestone marks another opportunity for Merck to build on our respiratory heritage with allergy specialists.”

In May, FDA approved Zontivity for the reduction of thrombotic cardiovascular events in patients with a history of heart attack (myocardial infarction) or in patients with narrowing of leg arteries, called peripheral arterial disease. For patients with a history of heart attack or with PAD who had no history of stroke or transient ischemic attack, Zontivity added to standard of care produced a significant 17 percent relative risk reduction over the three years of the study for the combined events of cardiovascular death, myocardial infarction, stroke, and urgent coronary revascularization. For the key secondary composite efficacy endpoint of CV death, MI, and stroke alone, Zontivity produced a significant 20 percent relative risk reduction in these patients. These results were driven by an 18 percent relative risk reduction in MI and a 33 percent relative risk reduction in first stroke. Zontivity is the first therapy shown to inhibit the protease-activated receptor-1 (PAR-1), the primary receptor for thrombin, which is considered to be the most potent activator of platelets. The PAR-1 pathway participates in the formation of blood clots through the activation and aggregation of platelets. Zontivity addresses this additional pathway that is not targeted by aspirin or P2Y12 inhibitors, like Plavix.

In August, FDA approved Belsomra for adults with insomnia who have difficulty falling asleep and/or staying asleep. Belsomra is a highly selective antagonist for orexin receptors. Orexin is a neurotransmitter found in a specific part of the brain that can help keep a person awake. The mechanism by which Belsomra exerts its therapeutic effect is presumed to be through antagonism of orexin receptors. In the clinical trials to support efficacy, the compound was superior to placebo for sleep latency and sleep maintenance as assessed both objectively by polysomnography and subjectively by patient-estimated sleep latency. FDA has recommended that Belsomra be classified by the U.S. Drug Enforcement Administration as a scheduled product. Earlier this year, the DEA proposed a Schedule IV drug classification under the Controlled Substances Act. The DEA has not yet issued a final decision on the scheduling for Belsomra and therefore product cannot become available before that decision.

“Today’s approval of Belsomra allows for the introduction of a new treatment option for patients suffering from insomnia,” said Dr. David Michelson, VP, Neurosciences, Merck Research Laboratories, on announcement of the approval. “Belsomra is the result of more than a decade of Merck research in neuroscience and provides tangible evidence of our long-standing commitment to innovation.”

Most prominently of all, in September FDA approved Keytruda for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. The indication was granted under accelerated approval based on tumor response rate and durability of response; an improvement in survival or disease-related symptoms has not yet been established.

Keytruda is the first anti-PD-1 (programmed death receptor-1) therapy approved in the United States and received FDA’s Breakthrough Therapy designation for advanced melanoma, which was granted based on the significance of early study findings and the unmet medical need. For the recommended two milligrams per kilogram dose based on data in 89 patients, the overall response rate was 24 percent, with one complete response and 20 partial responses. At the time of analysis, 86 percent of patients with objective responses had ongoing responses with durations ranging from 1.4-plus to 8.5-plus months, including eight patients with ongoing responses of six months or longer. Fourteen percent had progression of disease 2.8, 2.9, and 8.2 months after initial response. The compound remains in development for a number of other cancer types, including bladder, colorectal, gastric, head and neck, melanoma, non-small cell lung, renal, triple negative breast, and hematological malignancies.

“Keytruda embodies Merck’s unwavering commitment to pursue breakthrough science to help people who are facing the most challenging diseases,” Mr. Frazier says. “We are grateful to the people with advanced melanoma who participated in our trials, and the scientific and medical community for the shared effort that has led to the accelerated approval of Keytruda.”

Several other Merck compounds are still awaiting decision by regulatory authorities. In September 2013, the company submitted an NDA for its investigational fertility treatment corifollitropinalfa. Merck is seeking FDA approval of corifollitropinalfa for controlled ovarian stimulation in women participating in assisted reproductive technology. If approved, corifollitropinalfa would be the first sustained follicular stimulant for use in a fertility treatment regimen. 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 corifollitropinalfa 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.”

In February, the biologics license application for V503, Merck’s investigational 9-valent human papillomavirus vaccine, was accepted for standard review by FDA. The application was based on results from a pivotal Phase III study, reported in November 2013, showing that V503 prevented approximately 97 percent of cervical, vaginal, and vulvar pre-cancers caused by HPV types 31, 33, 45, 52, and 58. V503 also generated immune responses to HPV types 6, 11, 16, and 18 that were non-inferior to those generated by Gardasil.

V503 includes five more HPV types (31, 33, 45, 52, 58) in addition to the four original HPV types (6, 11, 16, 18) in Gardasil.

Also, in June, FDA accepted an NDA for a fixed-dose combination of Isentress with lamivudine for the treatment of HIV-1 infection. Merck is seeking FDA approval for 150 milligrams lamivudine/300 milligrams Isentress, in combination with other antiretroviral agents, for the treatment of HIV-1 in adults, adolescents (16 years of age and older) and pediatric patients (6 through 16 years of age and weighing at least 30 killograms).

“We are pleased that the FDA has accepted our application for a fixed-dose combination of raltegravir [Isentress] and lamivudine,” says Dr. Nick Kartsonis, executive director, clinical research, Merck Research Laboratories. “This combination pairs two HIV medications and, if approved, will offer prescribers an additional option in the treatment regimens of HIV-1 patients. This filing is another example of Merck’s commitment to HIV.”

Several other compounds are still brewing in Merck’s late-stage development pipeline. In October 2013, FDA granted MK-5172/MK-8742 Breakthrough Therapy designation for the treatment of chronic hepatitis C virus infection. MK-5172/MK-8742 is an all-oral combination regimen consisting of MK-5172, an investigational HCV NS3/4A protease inhibitor, and MK-8742, an investigational HCV NS5A replication complex inhibitor. Then, in April, interim results from the ongoing C-WORTHy study, a Phase II clinical trial evaluating the efficacy and safety of the combination regimen showed that hard-to-cure patients administered MK-5172/MK-8742 with and without ribavirin for 12 or 18 weeks showed sustained viral response four to eight weeks after the completion of therapy.

“The designation of MK-5172/MK-8742 as a Breakthrough Therapy for chronic hepatitis C is an important milestone for Merck,” Dr. Perlmutter says. “There remains significant unmet medical need in hepatitis C, and we are looking forward to working with the FDA to advance this program as quickly as we can to bring this investigational combination to HCV specialists and their patients.”

In December, the company provided an update on the development program for MK-8931, a novel investigational oral beta-amyloid precursor protein site-cleaving enzyme (BACE) inhibitor. The data monitoring committee for the Phase II/III EPOCH study of MK-8931 in patients with mild to moderate Alzheimer’s disease had recently completed its planned interim safety analysis and recommended that the trial continue to recruit patients, with no changes to the protocol. The DMC recommendation was made following a planned analysis of interim safety data that included a safety cohort of 200 patients treated with MK-8931 for at least three months. Based upon the DMC’s recommendations, Merck will continue enrollment of the EPOCH study. In addition, Merck will initiate dosing in a new Phase III study (APECS study) evaluating MK-8931 in patients with amnestic mild cognitive impairment due to Alzheimer’s disease, also known as prodromal Alzheimer’s disease.

“We are pleased to receive the DMC’s recommendation and look forward to continuing the clinical development program for MK-8931,” Dr. Michelson says. “Studies to evaluate potential new treatment options are critical as the global health and financial burden of Alzheimer’s disease grows.”

In March, Merck presented data from the dose-ranging portion of an ongoing Phase IIb clinical trial of doravirine, the company’s investigational next generation non-nucleoside reverse transcriptase inhibitor, demonstrating potent antiretroviral activity for four doses (25, 50, 100, and 200 milligrams) of once-daily, oral doravirine in combination with tenofovir/emtricitabine in treatment-naïve, HIV-1 infected adults after 24 weeks of treatment. Based on these findings as well as other data from the doravirine clinical program, Merck plans to initiate a Phase III clinical trial program for doravirine in combination with ARV therapy in the second half of 2014.

In June, Merck announced results from a global, investigational Phase III study to evaluate the safety and efficacy of Emend in the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients, aged 6 months to 17 years. In this study in pediatric cancer patients undergoing very highly, highly, or moderately emetogenic (vomit-inducing) chemotherapy, the use of the Emend regimen for CINV prevention was significantly more effective than a control regimen in achieving complete response, defined as no vomiting or retching and no use of rescue medication for nausea and vomiting, in all phases of CINV (acute, delayed, and overall). Emend is already indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin; and for prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

In July, the company launched a global Phase III clinical study of letermovir (MK-8228), an investigational antiviral agent. The multicenter, randomized, placebo-controlled study is evaluating the efficacy and safety of letermovir for the prevention of clinically significant cytomegalovirus infection in adult CMV seropositive recipients of allogeneic hematopoietic stem cell transplants. In the study, letermovir is being administered once daily, either as an oral tablet or IV formulation, for 14 weeks after transplant. The dose is 240 milligrams once daily for participants receiving concomitant cyclosporin A and 480 milligrams once daily for participants not receiving cyclosporin A. The primary outcome measure of the study will be the percentage of participants with clinically-significant CMV infection through 24 weeks after transplant who were administered letermovir compared to placebo. The estimated study completion date is July 2017.

“There remains a need for additional therapeutic options in the prevention of CMV infection in high-risk patients,” says Dr. Michele Trucksis, executive director, Infectious Diseases, Merck Research Laboratories. “Merck is pleased to initiate this global Phase III study with letermovir.”

In September 2014, Merck announced data from the pivotal Phase III fracture outcomes study for odanacatib in postmenopausal women with osteoporosis. Odanacatib is Merck’s investigational once-weekly cathepsin K inhibitor. In the Long-Term Odanacatib Fracture Trial (LOFT), odanacatib met its primary endpoints and significantly reduced the risk of osteoporotic hip, spine and non-vertebral fractures compared with placebo. The rates of adverse events overall in LOFT were generally balanced between patients taking odanacatib and placebo. Adjudicated events of morphea-like skin lesions and atypical femoral fractures occurred more often in the odanacatib group than in the placebo group. Adjudicated major adverse cardiovascular events were generally balanced overall between the treatment groups. There were numerically more adjudicated stroke events with odanacatib than with placebo.

“Merck believes the currently available data support a favorable benefit/risk profile for odanacatib,” says Dr. Keith Kaufman, vice president, Clinical Research, Diabetes and Endocrinology, Merck. “We want to thank our investigators who conducted the study and the thousands of patients who participated in this study, which is yielding critical insights into the potential of odanacatib in the treatment of postmenopausal osteoporosis.”

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