Merck’s newest immuno-oncologic is providing much-needed hope to a portfolio full of stagnant sales numbers.
Merck & Co.
2000 Galloping Hill Road
Kenilworth, NJ 07033
|Product||2015 Sales||2014 Sales|
|Gardasil, Gardasil 9||
All sales are in millions of dollars.
In millions of dollars, except EPS
It would be difficult to call Merck’s product portfolio over the past several years anything but stagnant. The company’s revenue has declined every year since peaking at just over $48 billion in 2011, and in 2015 it fell below $40 billion for the first time since the Schering-Plough merger in 2009. Seven of Merck’s top 10 products, including heavyweights like Januvia, Zetia, Remicade, Isentress and Vytorin, suffered sales declines in 2015, and none had growth of more than 10 percent. In short, the weather has been rough in North Jersey.
There is one shining bright spot in Merck’s portfolio, though, and that is the promising new immuno-oncologic Keytruda. After earning its first FDA approval in September 2014, Keytruda generated more than $500 million in its first full year on the market, and looks like a strong bet to cross the billion-dollar mark this year. The ceiling for Keytruda remains to be determined, but Merck is clearly betting heavily on the drug, with a clinical program across more than 30 tumor types and more than 200 trials.
“As we accelerate the launch of Keytruda around the world, our researchers are continuing to study Keytruda with an extensive clinical development program that spans a multitude of cancer types,” said Merck CEO Kenneth Frazier during the company’s 2Q16 earnings call. “We’re confident that Keytruda will be a key treatment in cancer for many years to come.”
Merck’s top-line revenue was $39.5 billion in 2015, a decline of 6.5 percent. Net income declined by more than half, from $11.93 billion to $4.46 billion, though the 2014 number includes a one-time gain of more than $10 billion from the divestiture of Merck Consumer Care. In the first half of 2016, top-line revenue was basically stagnant, falling 0.3 percent to $19.16 billion. Net income rose 42.1 percent to $2.34 billion, though this too was impacted by a one-time event, a $715 million devaluation of Merck’s assets in Venezuela in the second quarter of 2015. Merck executives are projecting full-year EPS for 2016 at between $1.98 and $2.08.
The diabetes product Januvia remained on top of Merck’s portfolio in 2015 – but sales of the drug fell off again, by 1.7 percent to $3.86 billion. At the same time, Januvia’s sister drug Janumet grew its sales by 3.9 percent to $2.15 billion. According to company leaders, Januvia/Janumet’s sales performance reflected higher volumes and pricing in the United States, as well as volume growth in the emerging markets and Europe, minus a 7 percent unfavorable effect of foreign exchange. In the first half of 2016, sales of Januvia rose 2.2 percent to $1.97 billion, while sales of Janumet edged up 1.1 percent to $1.08 billion.
Sales of Merck’s two leading cholesterol drugs, Zetia and Vytorin, both declined in 2015, with Zetia dropping 4.7 percent to $2.53 billion and Vytorin down 17.5 percent to $1.25 billion. According to company leaders, this was driven by a 7 percent unfavorable effect of foreign exchange as well as the loss of market exclusivity in Canada in September 2014. In the first half of 2016, sales of Zetia rose 9.3 percent to $1.31 billion, while sales of Vytorin were down 10.9 percent to $570 million.
In February, FDA issued a Complete Response Letter regarding Merck’s Supplemental New Drug Applications for Zetia and Vytorin for the reduction of the risk of cardiovascular events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, or need for revascularization) in patients with coronary heart disease. The applications were based on the results of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial). Merck is reviewing the letter and will determine next steps.
Merck’s HPV vaccines Gardasil and Gardasil 9 generated combined sales of $1.91 billion in 2015, an improvement of 9.8 percent. Sales growth was driven primarily by higher sales in the United States resulting from higher pricing and increased volumes reflecting the timing of public sector purchases, as well as increased government tenders in the Asia Pacific region, partially offset by declines in Latin America due to both price and volume. In the first half of 2016, sales of the Gardasil vaccines declined by 1.9 percent to $770 million.
The autoimmune product Remicade suffered a significant fall-off in 2015, with sales dropping 24.4 percent to $1.79 billion. This was partially due to a 14 percent unfavorable effect of foreign exchange, as well as Remicade’s dubious distinction of being the first autoimmune drug to encounter biosimilar competition, after the approval of Remsima in Europe in late 2013. At the same time, sales of Remicade’s follow-on Simponi were basically flat at $690 million. In the first half of 2016, sales of Remicade declined even more sharply, falling 28 percent to $688 million – FDA approved a biosimilar for the drug, Inflectra, in April, and the European Commission approved a second, Flixabi, the following month – while sales of Simponi rose 18.3 percent to $387 million.
Sales of the HIV product Isentress declined by 9.7 percent to $1.51 billion in 2015. This included an 8 percent unfavorable effect of foreign exchange plus lower volumes in the United States and lower demand and pricing in Europe due to competitive pressures, partially offset by higher volumes in Latin America and higher pricing in the United States. In the first half of 2016, sales of Isentress were $678 million, a decline of 10.8 percent.
In July, Merck announced efficacy and safety data in previously untreated adults with HIV-1 infection for the company’s investigational once-daily formulation of Isentress known as raltegravir 600 mg (to be given as 2 x 600 mg), from the ongoing Phase III pivotal trial called ONCEMRK. The study found that after 48 weeks of treatment, 1200 mg raltegravir (given as 2 x 600 mg once-daily) was statistically non-inferior (88.9 percent) to the marketed formulation approved dose of Isentress 400 mg twice-daily (88.3 percent), each in combination therapy with Truvada; with a treatment difference of 0.5, as assessed by the proportion of patients achieving less than 40 copies/mL of HIV RNA. Furthermore, the study showed comparable rates of reported drug-related clinical adverse events and rates of discontinuation between the two treatment groups. Based on these results from Week 48 of the ONCEMRK study, the European Medicines Agency has accepted the file for the investigational once-daily formulation of Isentress for review. Merck plans to submit applications in several countries, including the United States by year-end 2016.
The antibiotic Cubicin, acquired in the January 2015 Cubist transaction, generated $1.13 billion in sales for Merck in 2015. Cubicin is indicated for the treatment of complicated skin and skin structure infections or bacteremia, when caused by designated susceptible organisms. In the first half of 2016, Cubicin sales rose 35.2 percent to $649 million; however, the product lost U.S. patent protection in June, so sales for the rest of the year are expected to decline.
Merck’s most impressive rising star in 2015 was the immuno-oncology drug Keytruda. After earning its first FDA approval in September 2014, for the treatment of advanced melanoma in patients with disease progression after other therapies, Keytruda earned $566 million in its first full calendar year on the market and nearly matched that in the first half of 2016 alone, with another $563 million in sales. During the course of 2015, FDA approved Keytruda for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 as determined by an FDA-approved test and who have disease progression on or after platinum-containing chemotherapy, and approved an expanded indication to include the first-line treatment of patients with unresectable or metastatic melanoma. The European Commission also approved Keytruda for the treatment of advanced (unresectable or metastatic) melanoma in adults. Merck’s clinical trials program for Keytruda includes more than 30 tumor types in more than 200 clinical trials, including over 100 trials that combine Keytruda with other cancer treatments.
In April, FDA granted Breakthrough Therapy Designation to Keytruda for treating patients with relapsed or refractory classical Hodgkin lymphoma. This was the fourth Breakthrough Therapy Designation granted for Keytruda; it was previously granted breakthrough status for specific patients with advanced melanoma, advanced non-small cell lung cancer, and advanced colorectal cancer. The Breakthrough Therapy Designation in cHL was based on data from the ongoing Phase Ib KEYNOTE-013 and Phase II KEYNOTE-087 studies evaluating single agent Keytruda in patients with cHL.
In June, Merck announced that the KEYNOTE-024 trial investigating the use of Keytruda in patients with previously untreated advanced non-small cell lung cancer whose tumors expressed high levels of PD-L1 (tumor proportion score of 50 percent or more), met its primary endpoint. In this trial, Keytruda was superior compared to chemotherapy for both the primary endpoint of progression-free survival, and the secondary endpoint of overall survival. Based on these results, an independent Data Monitoring Committee recommended that the trial be stopped, and that patients receiving chemotherapy in KEYNOTE-024 be offered the opportunity to receive Keytruda.
In August, FDA approved Keytruda at a fixed dose of 200 mg every three weeks for treating patients with recurrent or metastatic head and neck squamous cell carcinoma with disease progression on or after platinum-containing chemotherapy. Under FDA’s accelerated approval regulations, this indication is approved based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. For HNSCC patients, PD-L1 testing is not needed prior to use of Keytruda.
The approval is based on data from the KEYNOTE-012 study, which included patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy or following platinum-containing chemotherapy administered as part of induction, concurrent, or adjuvant therapy and ECOG performance status of zero or one. The data showed an objective response rate of 16 percent and complete response rate of five percent, with responses of six months or longer observed in 82 percent of the responding patients. ORR and duration of response were similar regardless of human papilloma virus status.
Additionally in August, the European Commission approved Keytruda, at a dose of 2 mg/kg every three weeks, for patients with locally advanced or metastatic non-small cell lung cancer in patients whose tumors express PD-L1 and who have received at least one prior chemotherapy regimen. The approval was based on findings from KEYNOTE-010, a pivotal study which showed Keytruda significantly improved overall survival compared to standard of care chemotherapy.
During September, FDA accepted for Priority Review the supplemental Biologics License Application for Keytruda for the first-line treatment of patients with advanced non-small cell lung cancer whose tumors express PD-L1, with a PDUFA date of December 24, 2016. Additionally, the FDA granted Breakthrough Therapy Designation for this indication. The submission was based on data from the KEYNOTE-024 trial, referenced earlier.
Acquisitions & Collaborations
In January, Merck announced the acquisition of IOmet, a privately held UK-based drug discovery company focused on the development of innovative medicines for the treatment of cancer, with a particular emphasis on the fields of cancer immunotherapy and cancer metabolism. Under terms of the agreement, Merck, through a subsidiary, will acquire IOmet, including its comprehensive pre-clinical pipeline of IDO (indoleamine-2,3-dioxygenase 1), TDO (tryptophan-2,3-dioxygenase), and dual-acting IDO/TDO inhibitors. Based on the transaction, IOmet will become a wholly owned subsidiary of Merck.
IDO1 and TDO, the rate-limiting enzymes in the pathway that metabolizes the essential amino acid tryptophan, have emerged as key targets in the cancer immunotherapy field. Overexpression of these enzymes has been detected in a variety of cancers – including glioma, melanoma, lung, ovarian, and colorectal – and is associated with poor prognosis and survival. IDO1 and TDO overexpression leads to tryptophan depletion and high tumor levels of the breakdown product, kynurenine. This elevated kynurenine/tryptophan ratio suppresses the body’s immune response to cancer, thus facilitating tumor progression and metastasis. Extensive preclinical evidence, and emerging clinical data, suggest that inhibition of IDO1 and/or TDO may synergize with, and help overcome resistance to, existing clinical cancer therapies, in particular other immunotherapy-based treatments.
In March, Merck and Sanofi Pasteur announced their intent to end their joint vaccines operations in Europe. Upon concluding their joint venture, both companies plan to integrate their respective European vaccine businesses into their operations, independently manage their product portfolios, and pursue their own distinct growth strategies in Europe. The joint venture Sanofi Pasteur MSD, owned on a 50/50 basis by Sanofi Pasteur and MSD, was created in 1994 to develop and commercialize vaccines originating from both companies’ pipelines to improve and promote public health in 19 European countries. According to company leaders, the conclusion of the joint venture should be complete by the end of 2016.
During June, Merck signed a definitive agreement to acquire Afferent Pharmaceuticals. According to company executives, Afferent is a leader in the development of therapeutic candidates targeting the P2X3 receptor for the treatment of common, poorly-managed, neurogenic conditions. Afferent’s lead investigational candidate, AF-219, is a selective, non-narcotic, orally-administered P2X3 antagonist currently being evaluated in a Phase IIb clinical trial for the treatment of refractory, chronic cough as well as in a Phase II clinical trial in idiopathic pulmonary fibrosis with cough.
Merck, through a subsidiary, will acquire all outstanding stock of Afferent in exchange for an upfront payment of $500 million in cash. Also, Afferent shareholders will be eligible to receive a total of up to an additional $750 million associated with the attainment of certain clinical development and commercial milestones for multiple indications and candidates, including AF-219.
Also in June, Merck and Moderna Therapeutics announced a strategic collaboration and license agreement to develop and commercialize novel messenger RNA-based personalized cancer vaccines. According to company leaders, the collaboration combines Merck’s established leadership in immuno-oncology with Moderna’s pioneering mRNA vaccine technology and GMP manufacturing capabilities to advance individually tailored cancer vaccines for patients across a spectrum of cancers.
Moderna and Merck are developing personalized cancer vaccines that utilize Moderna’s mRNA vaccine technology to encode a patient’s specific neoantigens, unique mutations present in that specific patient’s tumor. When injected into a patient, the vaccine will be designed to elicit a specific immune response that will recognize and destroy cancer cells. The companies believe that the mRNA-based personalized cancer vaccines’ ability to specifically activate an individual patient’s immune system has the potential to be synergistic with checkpoint inhibitor therapies, including Merck’s anti-PD-1 therapy Keytruda. In addition, Moderna has developed a rapid cycle time, small-batch manufacturing technique that will uniquely allow the company to supply vaccines tailored to individual patients within weeks.
Under the terms of the agreement, Merck will make an upfront cash payment to Moderna of $200 million, which Moderna will use to lead all research and development efforts through proof of concept. The development program will entail multiple studies in several types of cancer and include the evaluation of mRNA-based personalized cancer vaccines in combination with Keytruda. Moderna will also use the upfront payment to fund a portion of the build-out of a GMP manufacturing facility in suburban Boston for the purpose of personalized cancer vaccine manufacturing.
Following human proof of concept studies, Merck has the right to elect to make an additional undisclosed payment to Moderna. If exercised, the two companies will then equally share cost and profits under a worldwide collaboration for the development of personalized cancer vaccines. Moderna will have the right to elect to co-promote the personalized cancer vaccines in the United States. The agreement entails exclusivity around combinations with Keytruda. Moderna and Merck each have the ability to combine mRNA-based personalized cancer vaccines with other (non-PD-1) agents.
Also in June, Merck and Premier Inc., a healthcare improvement company, agreed to collaborate on the co-development of solutions to help improve population health. Initially, the companies are focused on reducing fracture rates for at-risk osteoporosis patients. According to company leaders, the collaboration agreement combines expertise and assets from Merck, Premier’s performance improvement framework and analytics, Premier’s alliance of health systems, and other healthcare leaders to jointly develop and test effective solutions to help improve patient care and wellness, and lower healthcare spending.
Merck and Premier are working with the National Osteoporosis Foundation to co-develop and test performance improvement solutions, including educational initiatives that are designed to help improve the quality of care for diagnosed untreated patients at risk of osteoporotic fracture. By finding ways to better identify, assess, and treat these patients at risk for fractures, this collaboration seeks to reduce the incidence and burden of osteoporotic fractures for both patients and society.
As part of the project, the organizations are working to identify a core set of metrics for osteoporosis care and fracture prevention that align with measures endorsed by the National Quality Forum, as well as other quality measures such as Physician Quality Reporting System measures. The collaboration integrates Premier’s CECity quality improvement analytics platform, the measure set, as well as interventions for improvement such as virtual collaboration community tools and performance reports, into a cloud-based application to be automated and tested within volunteer Premier member health systems.
Recent Approvals/In The Pipeline
In January, FDA accepted for review the biologics license application for bezlotoxumab, an investigational antitoxin for prevention of Clostridium difficile infection recurrence. FDA granted Priority Review for bezlotoxumab, with a Prescription Drug User Fee Act action date of July 23, 2016. In July, FDA requested the submission of new data and analyses from the MODIFY I and MODIFY II clinical trials. The additional data and analyses constituted a major amendment to the BLA, resulting in an extension of the PDUFA goal date by three months to October 23, 2016. Merck has also filed a marketing authorization application for bezlotoxumab with the European Medicines Agency that is currently under review. The application for bezlotoxumab is based in part on data from the pivotal MODIFY I and MODIFY II clinical trials.
Also in January, Merck confirmed the completion of enrollment for the EPOCH trial, a Phase II/III randomized, placebo-controlled, parallel-group, double-blind study of the company’s investigational oral small molecule selective beta secretase inhibitor verubecestat – formerly known as MK-8931 – in patients with mild-to-moderate Alzheimer’s disease. The ongoing study, begun in November 2012, completed enrollment in the fourth quarter of 2015 and is estimated to reach primary trial completion in July 2017.
The ongoing EPOCH study is designed to evaluate the safety and efficacy of two oral doses of verubecestat (12 mg and 40 mg) administered once daily versus placebo in patients with mild-to-moderate AD currently using standard of care treatment. The primary efficacy outcomes of the study are the change from baseline in the Alzheimer’s Disease Assessment Scale Cognitive Subscale score, as well as the change from baseline in the Alzheimer’s Disease Cooperative Study – Activities of Daily Living score, following 78 weeks of treatment. Merck is also investigating the safety and efficacy of verubecestat in the earlier, prodromal phase of AD in an additional Phase III clinical trial called APECS.
Also in January, FDA approved Zepatier (elbasvir and grazoprevir) for the treatment of adult patients with chronic hepatitis C virus genotype 1 or GT4 infection, with or without ribavirin, following priority review. Zepatier is a once-daily, fixed-dose combination tablet containing the NS5A inhibitor elbasvir (50 mg) and the NS3/4A protease inhibitor grazoprevir (100 mg). FDA previously granted two Breakthrough Therapy designations to Zepatier, for the treatment of chronic HCV GT1 infection in patients with end stage renal disease on hemodialysis, and for the treatment of patients with chronic HCV GT4 infection. Across multiple clinical studies, Zepatier achieved high rates of sustained virologic response ranging from 94 to 97 percent in GT1-infected patients, and 97 to 100 percent in GT4-infected patients.
Merck’s broad clinical trial program supporting the efficacy of Zepatier included six studies in 1,373 patients with chronic HCV GT1 or GT4 infection. These studies assessed the rate of sustained virologic response 12 weeks after the completion of treatment with Zepatier. The clinical development program for Zepatier enrolled diverse groups of HCV GT1 and GT4-infected patients, including treatment-naïve patients and those who had failed prior therapy with peginterferon alfa and RBV, as well as patients suffering with meaningful co-morbidities and health complications, such as compensated cirrhosis and HIV-1 co-infection. GT1-infected patients with severe renal impairment on hemodialysis and those who previously failed therapy with PegIFN and RBV in combination with an HCV NS3/4A protease inhibitor (boceprevir, simeprevir, or telaprevir) also were studied.
In February, Merck and Pfizer Inc. announced that a Phase III study (VERTIS SITA2) of ertugliflozin, an investigational oral SGLT2 inhibitor for the treatment of patients with type 2 diabetes, met its primary endpoint. Both 5 milligram and 15 milligram daily doses of ertugliflozin showed significantly greater reductions in A1C of 0.69 percent and 0.76 percent, respectively, compared with placebo, when added to patients on a background of sitagliptin (100 mg/day) and stable metformin (≥1500 mg/day). Merck and Pfizer plan to submit NDAs to FDA for ertugliflozin and two fixed-dose combinations (ertugliflozin plus Januvia and ertugliflozin plus metformin) by the end of 2016, with additional regulatory submissions outside of the U.S. to follow in 2017.
In this double-blind, randomized, placebo-controlled study, 463 patients with type 2 diabetes and a baseline A1C of 7 – 10.5 percent were randomized to receive ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo in a 1:1:1 ratio. In addition to meeting the primary endpoint of reducing A1C at 26 weeks, a greater proportion of patients taking ertugliflozin 5 mg and 15 mg achieved the A1C treatment goal of less than 7 percent (32.1 percent and 39.9 percent, respectively) compared with the placebo group (17 percent).
In April, FDA accepted for review the Biologics License Application for MK-8237, Merck’s house dust mite sublingual allergy immunotherapy tablet. The BLA for Merck’s investigational house dust mite SLIT-tablet was supported by a comprehensive clinical program involving more than 4,000 patients, including two Phase III in-field trials that evaluated the efficacy and safety of MK-8237 in house dust mite-induced allergic rhinitis with or without conjunctivitis. Merck’s house dust mite SLIT-tablet is an investigational sublingual immunotherapy dissolvable tablet designed to help treat allergic rhinitis with or without conjunctivitis caused by house dust mite-specific allergens. Merck has partnered with ALK-Abelló to develop its house dust mite SLIT-tablet in North America.
In May, FDA accepted for review a Biologics License Application submitted by Samsung Bioepis Co. for SB2 (infliximab), an investigational biosimilar candidate of Remicade. This BLA is the first application filed in the United States by Samsung Bioepis as part of its partnership with Merck to offer biosimilar alternatives to existing biologic medicines. The application seeks approval for use in all therapeutic indications currently approved for Remicade for which marketing exclusivity has expired.
Merck and Samsung Bioepis announced in February 2013 a development and commercialization agreement under which Merck will commercialize multiple biosimilar candidates in certain partnered territories. Under terms of the agreement, Samsung Bioepis is responsible for preclinical and clinical development, process development and manufacturing, clinical trials and regulatory registration. Merck has full responsibility for commercialization of approved products resulting from the agreement.
In June, Merck announced that a Phase II study of the company’s investigational beta-lactamase inhibitor relebactam in combination with imipenem/cilastatin (an approved carbapenem antibiotic) in patients with complicated urinary tract infections met its primary endpoint. The addition of relebactam is designed to restore activity of imipenem against certain imipenem-resistant strains of Gram-negative bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae.
In the multicenter, double-blind Phase II study, 302 adult patients with complicated urinary tract infections (51.7 percent) or acute pyelonephritis (48.3 percent) were randomized to receive either relebactam 250mg, relebactam 125mg, or placebo, each given intravenously in combination with imipenem/cilastatin (IMI) 500mg every six hours for 4 to 14 days. Efficacy was evaluated at discontinuation of IV therapy, early follow-up, and late follow-up. The primary endpoint was the proportion of microbiologically evaluable patients with a favorable microbiological response at DCIV, assessed by non-inferiority testing with a 15 percent margin. Results were similar across treatment groups: relebactam 250mg + IMI (95.5 percent), relebactam 125mg + IMI (98.6 percent), and placebo + IMI (98.7 percent). Among microbiologically evaluable patients, 10.5 percent had imipenem-resistant Gram-negative infections at baseline.
In July, Merck announced two regulatory milestones for the company’s investigational vaccine for Ebola Zaire, V920. FDA granted the vaccine candidate Breakthrough Therapy Designation, and the European Medicines Agency has granted PRIME (PRIority MEdicines) status.
“The granting of Breakthrough Therapy Designation by the FDA and PRIME status by the EMA will enable us to continue to accelerate development of V920, and we greatly appreciate the collaboration of these agencies in moving this vaccine candidate forward in potentially meeting this public health need,” says Paula Annunziato, M.D., VP for clinical research, Merck Research Laboratories.
V920 was initially engineered by scientists from the Public Health Agency of Canada’s National Microbiology Laboratory and subsequently licensed to a subsidiary of NewLink Genetics Corp. In late 2014, when the peak of the Ebola outbreak in western Africa was at its worst, Merck licensed V920 from NewLink Genetics, with the goal of accelerating the development, licensure, and availability of this candidate vaccine. Since that time, Merck has worked closely with NewLink Genetics and a number of external collaborators to enable a broad clinical development program with funding from the U.S. government including the Department of Health and Human Service’s Biomedical Advanced Research Development Authority and the Department of Defense’s Defense Threat Reduction Program/Joint Vaccination Acquisition Program among others. Additional research evaluating V920 is under way.
In August, FDA accepted for review the New Drug Application for MK-1293, an investigational follow-on biologic insulin glargine candidate for the treatment of people with type 1 and type 2 diabetes, which is being developed by Merck with partial funding from Samsung Bioepis.The development program for MK-1293 was designed to meet rigorous regulatory standards for follow-on biologics of clinical and nonclinical safety, efficacy, and quality. In addition to Phase I studies assessing its pharmacokinetic and pharmacodynamic properties, the NDA submission for MK-1293 includes results of two Phase III studies , one conducted in people with type 1 diabetes, and one in people with type 2 diabetes; Lantus, the originator insulin glargine, was the active comparator in both studies.
The NDA was filed through the 505(b)(2) regulatory pathway, which allows FDA to reference previous findings of safety and efficacy for an already-approved product, in addition to reviewing findings from studies of MK-1293. Separately, the Marketing Authorization Application for MK-1293, which Merck submitted to the European Medicines Agency in December 2015, is currently under review.
In September, Merck announced that it is discontinuing the development of odanacatib, an investigational cathepsin K inhibitor for osteoporosis, and will not seek regulatory approval for its use. Merck previously reported a numeric imbalance in adjudicated stroke events in the pivotal Phase III fracture outcomes study in postmenopausal women. The company has decided to discontinue development after an independent adjudication and analysis of major adverse cardiovascular events confirmed an increased risk of stroke.