Marketing proficiency and sales in the United States are important, of course, and Merck grew sales of Januvia/Janumet by
15 percent in 4Q of 2012, in the United States. But the brands grew by 25 percent ex-US during the same period. On an earnings
call in February, Adam Schechter, Merck's EVP, president, global human health, said 2012 full-year global sales of Januva/Janumet
hit $5.7 billion, making it the best selling product franchise in company history. Future growth will depend on key global
markets, and Merck appears to have the network and resources to make it happen. "There are only a couple of countries where
Januvia hasn't done spectacularly well" already, says Murray Aitken, executive director, IMS Institute for Healthcare Informatics.
Recognizing the higher instance of diabetes among Hispanic communities in the US, Merck created promotional and educational
materials tailored to Hispanic patients.
Thornberry says Merck put a focus on emerging markets, and has studied Januvia in Asian populations. This makes sense, given
the extraordinary number of diabetic patients in Asia. According to the International Diabetes Federation, China has the largest
diabetic population in the world, at over 92 million in 2012; in India, 63 million people have diabetes. El-Dada notes that
Merck has done additional studies in some Asian populations to gain approval, notably in Japan, where the dose for Januvia
is different. "We still have very robust double-digit growth in Europe, despite all of the austerity challenges there," says
El-Dada. "But if you look at where we're growing the fastest, from a regional perspective, it's Japan." El-Dada says Latin
America and the Middle East, in addition to Asia, are also areas of pronounced growth for Januvia.
In 2008, Merck partnered with Siemens for a diagnostic program to quickly identify potential Januvia patients outside of the
United States. The Siemens point-of-care program allows physicians working in clinics or private practices to measure a patient's
A1c levels—the key benchmark in determining whether the disease is being adequately controlled—in real-time. In the United
States, patients and physicians must wait for blood work to be processed in a lab to access A1c levels. Merck has since "rolled
[the Siemens partnership] out to 35 countries worldwide," says El-Dada. Since the program allows physicians to identify patients
with poorly-controlled diabetes during the first visit, Januvia can be prescribed on the spot, cancelling the need for a follow-up
appointment with the lab results.
In terms of reaching new markets, El-Dada says Januvia and Janumet have received approval in all of the major markets, although
the drug isn't approved in certain African geographies. "These are relatively small markets in terms of revenue impact, but
over the longer run, they'll matter more…we're continuing to do work [in African markets]." The company is also pursuing approval
for Janumet XR, as well as Juvicor (also called Juvisync), the sitagliptin/simvastatin combo, and is looking to enter emerging
markets with both products.
Januvia's autumn years: golden age or mid-life crisis?
Since Januvia's initial approval in 2006, FDA has approved a dozen new treatments for Type 2 diabetes, proof that better products
are still needed in the category. The agency approved three new drugs for Type 2 in the first month of 2013. Also in January,
an FDA advisory committee recommended (10-5) approval of J&J's canagliflozin. If approved, canagliflozin would become the
first in a new class of drugs—the much ballyhooed SGLT2 inhibitor class— and would compete directly with Januvia.
In such an increasingly competitive landscape, will middle-aged Januvia be able to continue building on its past success?
Both Januvia and Janumet have patent protection until 2022, says Thornberry. El-Dada and Thornberry cite Merck's clinical
study database, which includes outcomes data on over 20,000 patients globally, as critical to supporting the brand's future
success. A second pooled analysis of that data, covering safety and tolerability, will be published shortly, according to
Kim Hamilton, Merck's director of global human health communications. But questions about comparative efficacy with respect
to new products, in addition to new worries about pancreas-related side effects, have already begun to surface.
Based on post-market data, FDA added a warning about pancreatitis to Januvia's label in 2009, and at least two studies have
suggested a possible link to pancreatic inflammation and cancer. In a warning letter issued a year ago, FDA criticized Merck
for missing its deadline to conduct an animal study on pancreatitis risk associated with Januvia and Janumet. Merck has said
it will cooperate with FDA. As this article goes to press, a JAMA study analyzing insurance records concluded that Januvia "was associated with increased odds of hospitalization for acute
pancreatitis." Much has also been made about new competition to Januvia, including new DPP-4s, GLP-1s like Novo Nordisk's
Victoza, and the possibility of superior efficacy rates with canagliflozin (proposed brand name Invokana), should that drug
Despite unpredictable competitive market forces, safety scares and regulatory actions, most analysts remain bullish on the
Januvia franchise. Last summer, EvaluatePharma predicted that in 2018, Januvia/Janumet would be the world's top selling products,
with combined global revenues nearing $10 billon. The "Januvia family" currently holds over a 70 percent share of the global
DPP-4 market, Schecter said on the earnings call. "We know that this molecule maximally inhibits DPP-4, so we really don't
anticipate that any DPP-4 inhibitors will come along that have a greater efficacy than Januvia," says Thornberry, who also
alluded to post-hoc analyses and meta-analyses that point to a potential cardiovascular benefit for the DPP-4 class. Hamilton
hastens to add that the cardiovascular benefit is not conclusive as of yet. Is it possible that Januvia could one day, post-expiry,
be turned OTC? "I suppose it's possible," says Thornberry. "I think a drug like this where you have such a well-established
safety and tolerability profile…I wouldn't rule it out."