The Global Drug-Lag Problem

Tuesday, May 26, 2015

The Pulse on Global Trials by Matthew Howes

For all the advancements in medical research, certain regions of the world still wait to benefit from timely access to new drugs.

In a survey I conducted last fall, one respondent bemoaned the fact that Brazil still does not have crizotinib, Pfizer’s treatment for non-small cell lung cancer. The FDA cleared the drug for market in the U.S. under the brand name Xalkori in 2011. Drug lag, the time between when a product is approved and marketed in one country and when it is finally available in other countries, is a real problem.

Groundbreaking new medicines for hepatitis C (HCV) and drug-resistant tuberculosis (DR-TB) are two more examples of important medical innovations that remain out of reach for regions with the largest need. While these new drugs offer the potential to substantially simplify and improve treatment of the diseases, high prices and regulatory obstacles threaten to limit access. Often, the only way patients can gain access to new drugs outside the U.S. and Europe is through compassionate use or clinical access programs.

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For Middle Income Countries (MICs), the concern is particularly troubling. MICs collectively account for a large portion of global incidents of these diseases. Of the estimated 150 million people worldwide with HCV, for example, about 75% live in MICs.

While voluntary license agreements between manufacturers and foreign governments to produce affordable versions of their products are helpful, they often exclude MICs because they have passed the thresholds for per capita income. As countries expand their economies, changing status from emerging market to MIC, they effectively disenfranchise their populations from much needed, costly medicines. 

Pricing, though, is just one barrier to access. Equally challenging for all countries, not only MICs, are internal regulatory hurdles and lack of a single, global regulatory body to streamline the approval process. Optimizing time to approval has been a struggle for regulators for decades.

A recent study in Japan investigated the status of drug lag for oncology products. In a review of 120 applications, the median difference over a 13-year period in the approval date between the U.S. and Japan was 29 months. The lag peaked in 2002 and leveled out at nine months in 2014.

The reduction in lag time from 2001 to 2014 can be attributed to the emergence of molecularly targeted drugs as the predominant focus of oncology R&D and the shift from full development in Japan to global simultaneous development by Japan’s participation in global clinical trials.

The U.S. arguably has made the biggest strides in improving access to novel therapies. In the 1980s, less than 10% of all new compounds were launched first in the U.S. before anywhere else in the world. Today, more than two thirds of new drugs are approved in the U.S. first. According to the Center for Innovation in Regulatory Science, the FDA approves new drugs more quickly than any other regulator, and has consistently done so for the past 10 years.

But just because the time to approval has decreased in countries such as the U.S. and Japan doesn’t mean the effects of drug lag are limited to emerging markets and MICs. There are several examples in which this challenge is felt in the U.S. 

Bexsero, a vaccine to prevent invasive meningococcal disease caused by N. meningitidis serogroup B, was approved in Europe, Australia and Canada in 2012.  It took the FDA nearly three years longer to approve it in the U.S.

Esbriet, a treatment for Idiosyncratic Pulmonary Fibrosis, went on the market in Europe in 2011, but wasn’t approved by the FDA until late 2014, on the same day it approved a different drug for the same indication that had not yet been approved outside of the U.S.

Drug lag has a clear impact on patients. In the time between the approval of Esbriet in Europe and its approval in the U.S., some 150,000 patients with idiopathic pulmonary fibrosis in the U.S. did not have sanctioned access to the drug.

There’s also an economic impact. The inefficiency of requiring manufacturers to repeat studies and applications means precious R&D dollars are wasted undertaking multiple trials of the same medicines for different regulators.

In March, Congress introduced legislation that would require the FDA to expedite the review and approval of pharmaceutical products already approved in Europe. Should it become law, the bill would necessitate a form of reciprocity between regulators in the U.S. and E.U.

The FDA currently works in limited fashion with international bodies to harmonize regulations, but this new mandate would encourage regulatory and scientific competition between agencies. Some economists believe this would benefit consumers, who would gain faster access to new medicines, potentially at lower prices. 

Matthew Howes is senior vice president, marketing innovation for PALIO, an inVentiv Health company. A leader in digital strategy, he has provided the fuel for digital businesses visited by over 100 million people every month. Email

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