FirstWord Lists – The drugs that will shape 2014

Sovaldi – Hepatitis C (Gilead Sciences)

Approved by the FDA in December and the EMA on Friday, Gilead Sciences' Sovaldi is almost certain to become the fastest ever new drug launch over the next 12 months. Consensus estimates point to global sales of $2.5 billion in 2014.

Short-term performance will be driven in part by the notable warehousing of hepatitis C patients prior to the launch of Sovaldi, which will provide a virtual cure to many patients at a notably reduced duration of therapy (and in some cases without the need for interferon).

This year is also likely to witness the approval of Gilead's fixed-dose combination of Sovaldi and ledipasvir, which will dispense the requirement for interferon and ribavirin in most patients and may offer many the opportunity to be treated for just eight weeks.

Spotlight On: Biotechs are shunning biologics, say analysts; but will investors care if small molecules deliver big returns?

Physician Views Poll Results – No wonder payers are concerned; physicians enthused by labelling that allows Gilead Sciences' sofosbuvir/ribavirin combo to be administered to GT1 patients

Copaxone – multiple sclerosis (Teva)

Copaxone is not a new drug; indeed, it is coming to the end of its lifecycle. Nevertheless, the multiple sclerosis therapy is expected to play a prominent role in 2014 given the distinct possibility that generic competitors could finally emerge.

With patent exclusivity expiring in May in the US, debate as to whether the FDA will approve one or more generic Copaxone products rumbles on with no clear outcome, although analyst sentiment suggests that at least one approval should occur.

The future of Copaxone intersects two important narratives; the evolution of Teva (Copaxone accounts for around 20 percent of sales and 50 percent of profits) and the FDA's willingness to approve generic versions of more complex small-molecule pharmaceuticals. Teva's hopes to gain FDA approval for a less frequently dosed version of Copaxone by the end of the month.

Spotlight On: Teva steps up efforts to protect Copaxone brand as Mylan calls foul

Physician Views Poll Results – Generic Copaxone may struggle to gain market share in light of Teva's new formulation and oral switching trends

Kadcyla/Perjeta – HER2-positive breast cancer (Roche)

Roche investors are eagerly anticipating results from the MARIANNE study, which are due to be published in the second half of 2014.

Positive data – as is widely anticipated by analysts – should position the combination of Roche's newer therapies Kadcyla and Perjeta as the new gold-standard therapy for the first-line treatment of HER2-positive breast cancer, displacing the company's blockbuster product Herceptin in the process.

Not only would this outcome see the Swiss company once again improve the standard of available care for breast cancer patients, but positioning of a Kadcyla/Perjeta combination would significantly raise the bar for biosimilar developers; a strategy Roche is looking to replicate in the chronic lymphocytic leukaemia (CLL) market with Gazyva.

2013 In Review – Roche's biosimilar defence strategy gains momentum

Obeticholic acid (OCA) – Nonalcoholic steatohepatitis (Intercept Pharmaceuticals)

Is it too early to already consider Intercept Pharmaceuticals' nonalcoholic steatohepatitis (NASH) treatment obeticholic acid (OCA) one of the key drugs of 2014 in light of the company's recent surge in share price?

Cooler heads have prevailed since Intercept's shares shot up nearly 545 percent over a two-day period earlier this month, but the underlying fundamentals remain compelling. With NASH estimated to be prevalent in up to 10 percent of the US population, Intercept CEO Mark Pruzanski described the condition as "the next tsunami of liver disease," and bullish analysts describe NASH as being one of the last significant untapped disease areas. It's early days, but the prospect of further data and Phase III trial design for OCA later in 2014 – not to mention a notable partnering opportunity – make it one to watch.

ViewPoints: Intercept's staggering ascent provides early riposte to biotech rally doubters

Alirocumab (Regeneron Pharmaceuticals/Sanofi) and evolocumab (Amgen) – dyslipidaemia

The success of statins has largely precluded the pharma industry from making further strides in the dyslipidaemia market, but a number of companies are on the cusp of launching a new class of product that could provide a significant benefit to those patients in which statins are not effective.

This year is poised to deliver key news flow for the front-running products in the PSCK-9 inhibitor race being developed by Amgen and Sanofi/Regeneron Pharmaceuticals. Both products are expected to reach the market in late 2015, according to Bernstein analyst Geoffrey Porges, but the next few months will see data from up to a dozen Phase III studies released. The key objective? – to confirm the impressive mid-stage data that has seen analysts ascribe multi-billion sales potential to the PSCK-9 inhibitors.

ViewPoints: New treatment guidelines reshape the cardiovascular market opportunity; provide another challenge for the much touted PCSK9 inhibitor class

ViewPoints: Physician feedback indicates sizeable market for PCSK9 inhibitors, but more Phase III data needed to confirm efficacy in combination with statins

Nivolumab (Bristol-Myers Squibb), MK-3475 (Merck & Co.) and MPDL3280A (Roche) – melanoma, non-small-cell lung cancer and renal cancer

The revolutionary nature of the PD-1/PD-L1 inhibitors – and the obvious commercial opportunity of immunotherapy as a future treatment for multiple cancer types – means that leading drug candidates from Bristol-Myers Squibb, Merck & Co. and Roche will remain a key focus not only in 2014, but for many years to come.

June's ASCO annual meeting will see a wealth of new data presented across the immunotherapy space, but accurately predicting the regulatory movements of the front-running PD-1 inhibitors may prove difficult. Merck caught analysts and rivals unaware last week when it confirmed that a rolling submission for MK-3475 in Yervoy-refractory melanoma patients is under way, potentially leading to approval by year-end. On its part, the FDA is expected to move quickly given the tumour-shrinking credentials of MK-3475 and its race mates - ViewPoints: With something to prove, Merck & Co. comes out fighting in cancer immunotherapy race.

At a company level, for Bristol-Myers Squibb and Merck in particular, the PD-1 inhibitors represent key strategic catalysts; helping to shift the former to a more fully integrated specialty care model and providing the latter with a major fillip to R&D productivity.

In Focus: Bristol-Myers Squibb's R&D shake-up – A tale of two acquisitions

Imbruvica – Mantle cell lymphoma and chronic lymphocytic leukaemia (Johnson & Johnson/Pharmacyclics)

A noted key approval in 2013, and a poster child for the FDA's much discussed Breakthrough Therapy designation (it has received three), Imbruvica has been co-developed by Johnson & Johnson and Pharmacyclics and was approved by the FDA for the treatment of mantle cell lymphoma in December.

The next key short-term catalyst for Imbruvica is expected approval in chronic lymphocytic leukaemia (CLL) – a larger indication for which further positive clinical data were recently published and significant off-label use is thought to be occurring already. Imbruvica looks poised to emerge as one of a new generation of exciting products in the haematological malignancies space.

VX-809 (with Kalydeco) – Cystic fibrosis (Vertex Pharmaceuticals)

Vertex Pharmaceuticals revolutionised the treatment of cystic fibrosis with the launch of Kalydeco in 2012. The drug treats the approximate 2000 CF patients worldwide with the G551D gene mutation. Data released in December – which were designed to demonstrate efficacy in a further subset of around 1100 patients (R117H mutation) – was disappointing, but a key catalyst awaits in mid-2014.

Positive results from two Phase III studies – TRAFFIC and TRANSPORT – which are investigating Kalydeco in combination with a second drug, VX-809, would open up usage to the much larger F508del homozygous mutation (approximately 26,000 patients); the commercial implications of which are potential peak sales of $6 billion, estimate analysts.

Januvia – diabetes (Merck & Co.)

An unusual choice, perhaps, but as the most established type 2 diabetes treatment, the performance of Januvia over the next 12 months should act as something of a barometer for the dynamics of the broader 'oral' diabetes market.
Key catalysts in 2014 include the anticipated launch of new products from Eli Lilly (the GLP-1 agonist dulaglutide and the SGLT-2 inhibitor empagliflozin), GlaxoSmithKline's albiglutide (another GLP-1 agonist) and AstraZeneca's Farxiga; the recently approved and expected second-to-market SGLT-2 inhibitor.

AstraZeneca will assume control if its former joint venture from Bristol-Myers Squibb and will also look to revive its Bydureon franchise with the launch of a more convenient dual chamber pen device. Increased competition and a greater ability for payers to extract discounts will be key trends to watch.

Physician Views Poll Results – Aggressive formulary placing key to Farxiga's success in US diabetes market despite anticipated strong growth for SGLT-2 inhibitor class

Palbociclib – breast cancer (Pfizer)

The proposed – and much talked about – split of Pfizer would certainly allow new innovative products to have a greater impact on the revenue line. With recent launches Xeljanz (rheumatoid arthritis) and Eliquis (stroke; with Bristol-Myers Squibb) disappointing, however, the world's largest drug company also requires a compelling pipeline narrative.

Palbociclib is being tested across a number of tumour types, but its development has been prioritised in ER-positive, HER2-negative breast cancer, where initial Phase II studies have been completed (and data are due to be presented at ASCO). Phase III data should read-out in 2015, but some analysts maintain that palbociclib could be submitted for approval based on its mid-stage results, particularly as the drug has been granted Breakthrough Therapy status by the FDA. Analysts are bullish, some more than others; those at Morgan Stanley recently suggesting the drug could be bigger than Lipitor.

In Focus: Palbociclib – Pfizer's next blockbuster?

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