2014 in review – New drug approvals: what's the story? Morning glory!

The FDA approved a total of 41 new molecular entity (NME) and biologic license application (BLA) submissions in 2014, making it the most prolific year for new drug approvals since 1996, beating the recent high water mark of 39 product approvals in 2012. In 2013, the agency green-lit a comparatively modest 27 new products.

Based on a recent blog post in which FDA commissioner Margaret Hamburg provided a brief update on the administration's performance, the FDA has approved 16 new drugs to treat rare diseases (versus a previous record of 13 such approvals in one year) and at least 16 drugs that are first-in-class molecules. Hamburg noted at the time of the post in early December that 34 of the first 35 approvals in 2014 occurred on or before designated PDUFA dates, while more than 80 percent of actionable NMEs have been approved over the course of the year.

It is impossible to fully assess the health of industry R&D based solely on the number of new drug approvals, but the signs are positive. This trend is further enhanced by the FDA's approval of at least nine new drugs in 2014 that had previously received Breakthrough Therapy Designation (BTD): Novartis' Zykadia, Gilead Sciences' Zydelig and Harvoni, Merck & Co.'s Keytruda, Boehringer Ingelheim's Ofev, Roche's Esbriet, Amgen's Blincyto, AbbVie’s Viekira Pak and Bristol-Myers Squibb’s Opdivo. Given BTD status, these products arguably compete as the most important new approvals of 2014.

Gilead's Harvoni – approved in October for the treatment of genotype 1 hepatitis C – will rightly be lauded as the 'biggest' new drug of 2014 (Spotlight On: Four important talking points to watch now that Gilead's Harvoni is approved).

Preceded by the launch of Sovaldi in late 2013, Harvoni combines the active ingredient in that drug – sofosbuvir – with a second compound – ledipasvir. The result is a once-daily treatment for genotype 1 hepatitis C patients, which requires no exposure to interferon (or ribavirin for the majority of patients) and which in many cases can be prescribed over a duration of just eight weeks.

In its first full year on the market, Sovaldi is forecast to generate a staggering $11.7 billion in global sales, according to consensus estimates. With many eligible patients switching to Harvoni, sales of the combined Sovaldi/Harvoni franchise are expected to remain consistent at around $12.3 billion next year and are forecast to stand at around $12 billion in 2019.

Identifying the most 'important' new drug approval of 2014 is more challenging. Harvoni looked to be a solid candidate; Gilead has radically improved the way that hepatitis C is treated in just a few years. However, AbbVie’s Viekira Pak, the newly approved rival to Harvoni, likely stole away the ‘most important’ award in the dying days of December as AbbVie almost immediately sent shockwaves through the entire industry by announcing a deal with Express Scripts that most observers believe represent the first shot in a price war – a marketing tactic that most analysts and investors had believed the drugmaker would not pursue (ViewPoints: This means war! Impact of AbbVie's HCV deal with Express Scripts goes well beyond Gilead).

By tapping into latent fears that drug pricing – upon which a fair amount of the sector’s recent rise has been built – may not be as sustainable as previously imagined, the emergence of Viekira Pak has forcefully raised the key long-term question that the pharmaceutical industry will need to address.

The compelling competition in the HCV space has grabbed the headlines recently, but some may argue that the dual approvals of Merck's Keytruda and Bristol-Myers Squibb’s Opdivo are the most important of the past 12 months (Physician Views Poll Results: The PD-1 inhibitor class lands – how do US oncologists expect to initially use Merck & Co.'s Keytruda?).

The FDA’s approval of the Opdivo to treat unresectable or metastatic melanoma on December 22 was accelerated in more ways than one as it came almost three months ahead of the PDUFA date of March 25, 2015. The PD-1 inhibitor looks to be the second ‘biggest’ approval of 2014 just ahead of Keytruda thanks to expectations that the Bristol-Myers Squibb product will be first-to-market in lung cancer, which is expected to carry it to an estimated $4.4 billion in global sales by 2019.

While Opdivo received the first worldwide approval in Japan in June, Keytruda became the first of the class to receive regulatory clearance by the FDA in September to treat second-line metastatic melanoma. This breadth of application underscores why analyst consensus forecasts for Keytruda in 2019 stand at $3.3 billion, positioning Merck's drug as the likely third 'biggest' approval of last year.

In fact, this class of PD-1/PD-L1 therapies appears poised to deliver a significant breakthrough in the treatment of cancer. While the agents have demonstrated significant advancement in the future treatment of solid tumours, 2014 has also seen dramatic progress in the development of new therapies for haematological cancers – as illustrated by the enthusiastic reaction to data recently presented at the American Society of Hematology (ASH) annual meeting (FirstWord Lists: Brief look at compelling themes from this year's ASH meeting).

From a regulatory perspective, approval of Gilead's Zydelig for three different blood cancers continued the trend that saw Roche's Gazyva and Pharmacyclics/Johnson & Johnson's Imbruvica approved in late 2013. Furthermore, recent approval of Amgen's Blincyto further demonstrated the FDA's willingness to work rapidly in this area.

A handful of other 2014 approvals are expected to generate blockbuster status by the end of the decade, one of which is Roche's Esbriet for the treatment of idiopathic pulmonary fibrosis (IPF). The Esbriet narrative has a number of sub-plots, one being that it is the drug that convinced Roche to acquire InterMune for $8.3 billion in August, and another being that the FDA approved Boehringer Ingelheim's competing IPF therapy Ofev on the same day as Esbriet in October. Next year should witness, therefore, a compelling commercial battle in the IPF market (Physician Views Poll Results: The idiopathic pulmonary fibrosis (IPF) market – let battle commence).

To date, Eli Lilly and Merck have secured the joint-highest number of innovative FDA approvals in 2014, at three each. While Keytruda and Opdivo are standout approvals – as discussed above – it is Eli Lilly for which this tally is arguably more important with regard to overall performance over the next five years.

Ramucirumab is expected to be the largest new approval in terms of end-of-decade revenue, while both Trulicity and Jardiance (partnered with Boehringer Ingelheim) will support the company's position in an increasingly competitive diabetes market. As demonstrated by GlaxoSmithKline's disappointing performance this year, however, regulatory success (GlaxoSmithKline achieved six NME approvals in 2013) provides no guarantee of strong top-line growth.

Meanwhile, the European Medicines Agency recommended 82 medicines for marketing authorisation last year, up from 79 in 2013 and 57 in 2012.

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