The Friday Five – Five of the past week's stories you can't afford to ignore...

Cholesterol guidelines continue to spur much debate

Since being announced earlier this month, new treatment guidelines issued by the American Heart Association (AHA) and American College of Cardiology (ACC) have stimulated much debate.

The latest suggestion is that the new 'risk calculator' designed to assess which patients should receive therapy with a statin could overestimate the number of patients who fall into this category. Donald Lloyd-Jones, a cardiologist involved in writing the guidelines, has defended the calculator and also suggested that physicians should not be a 'slave' to it when making their decisions on who to treat – more here.

Data from a Physician Views poll run by FirstWord earlier this week indicates that cardiologists, general practitioners and internal medicine specialists are likely to take a cautious and measured approach to implementing the new guidelines - see Physician Views Poll Results – Implementation of new cholesterol guidelines likely to see moderate increase in statin prescription rate at best, alongside more caution towards PCSK9 inhibitors.

As such, respondents indicated that they expect only a moderate increase in the use of statins, although there did appear to be a strong view that new cholesterol-reducing drugs – such as the PCSK9 inhibitors – will be treated with more caution once launched, albeit until results from longer-term outcomes studies is published.

New data published on Wednesday by Amgen for its PCSK9 inhibitor evolocumab in combination with statin therapy further validates the clinical profile of these drugs, although uncertainties continue to cloud their regulatory and commercial outlook.

The FDA has suggested that LDL-cholesterol reduction remains a suitable endpoint for approval of drugs within the PCSK9 inhibitor class, but it may be that initial approval only occurs in specific patient populations with broader approval dictated by outcomes studies.

An earlier poll run by FirstWord suggests that physicians would be prepared to treat sizeable proportions of patient subsets who are 'not at goal' via statin therapy or whom are intolerant to these products (see Physician Views Poll Results – Awareness of PCSK9 inhibitors could be higher, but physicians ready to prescribe in hard-to-treat cardiovascular patients. Some analysts have noted, however, that not only is the statin-intolerant population poorly defined, but that the new guidelines may have also complicated the definition of patients who are 'not at goal,' given their shift away from treating towards a LDL-C target.

Anticipation builds for sofosbuvir approval – all eyes on early performance

FDA approval of Gilead Sciences' hepatitis C treatment sofosbuvir is imminent – it has a PDUFA date of December 8, but much speculation focuses on a potential green-light before the end of the month.

Although considered to be the key backbone therapy for the development of all-oral, interferon-sparing treatment regimens that could reach the market by late 2014, a Physician Views poll run by FirstWord this week indicates that significant uptake of sofosbuvir in combination with interferon and ribavirin could occur in the large genotype 1 patient subset prior to this - see Physician Views Poll Results – Convenient dosing and stronger than expected launch in 2014 to drive Gilead Sciences' dominance of hepatitis C market?

This is the second such poll to indicate that a larger than expected proportion of warehoused patients could be treated prior to the emergence of interferon-free therapies, which could reshape expectation for the 2015-16 period. Analysts at Wells Fargo also indicated in a note to investors this week that Gilead's own market research indicates notable pent up demand for sofosbuvir for use in genotype 1 patients. See also Physician Views Poll Results – Gilead Sciences' sofosbuvir could take significant share of warehoused HCV population prior to launch of interferon-free regimens.

Accurately gauging the warehoused population remains a challenge, although given that sales of Vertex's Incivek fell by nearly half between Q2 and Q3, anticipation for new therapies is clearly growing - see also Vertex Sells INCIVO Product Royalty Rights for $152 Million.

Biogen Idec faces European D-Day for Tecfidera

Friday should see the European Medicines Agency announce whether Biogen Idec has been successful in gaining regulatory data protection (RDP) for its multiple sclerosis treatment Tecfidera. A smash-hit with neurologists in the US – where it launched at the end of Q1 – the European data decision is widely seen as a binary event that will dictate whether Biogen Idec launches the drug in the region.

Physician Views poll data suggests notable warehousing of patients in anticipation for Tecfidera, which should result in a strong early performance for the drug should it launch in Europe - see FirstWord Physician Views: As Tecfidera approaches a critical juncture in Europe, how are neurologist perceptions towards Biogen Idec's MS drug shaping up?

Furthermore, analysts at Bank of America Merrill Lynch also pointed out this week that given the RDP issues, European consensus sales forecasts for Tecfidera have not increased since Q1, despite US sales being more than two-times higher than consensus estimates for 2013.

Merck & Co. delivers positive data for its key pipeline compound

Merck & Co. presented impressive melanoma survival data for MK-3475 this week and provided a timely reminder that it remains a key player in the immuno-oncology race.

Across all doses of MK-3475 in melanoma, the 12-month survival rate is tracking at around 81 percent, said International Strategy & Investment analyst Mark Schoenebaum in a note to investors on Monday. Crucially, this compares to an approximate 62 percent 12-month survival rate for Bristol-Myers Squibb's competing nivolumab and an 82 percent rate for nivolumab in combination with Bristol-Myers Squibb's approved melanoma therapy Yervoy.

The data certainly provide new context for the nivolumab plus Yervoy data, which generated both enthusiasm and debate in equal measure when released at the ASCO annual meeting earlier this year. Bristol-Myers Squibb used mWHO criteria (a bi-dimensional method) to measure tumour reduction, whilst Merck used RECIST criteria (a uni-dimensional method).

At ASCO, Antoni Ribas, lead investigator for Merck's MK-3475, argued that a 55 percent reduction using RECIST is approximately equivalent to an 80 percent reduction using mWHO, which Bristol-Myers Squibb defined as "near complete response." Ribas believes that MK-3475 monotherapy may have a comparable depth of response versus nivolumab and Yervoy in combination; a view supported to some extent by Merck's new interim data.

For further analysis see ViewPoints: New data give credibility to Merck & Co.'s bullishness in PD-1 race.

Key drugs in the news this week...

GlaxoSmithKline secured European approval for Relvar Ellipta (Breo Ellipta in the US). The European Commission has green-lighted the drug for use in asthma and chronic obstructive pulmonary disorder (COPD) versus a single COPD approval in the US. See also Physician Views Poll Results – European pulmonologists appear less receptive to once-daily LABA/ICS therapies than US counterparts for COPD.

Roche also secured European approval of Kadcyla as a second-line therapy for the treatment of HER2-positive breast cancer, some 8 months after the drug was approved by the FDA. Gilead Sciences' HIV portfolio was also boosted by European approval of its integrase inhibitor elvitegravir, which will be sold under the brand name Vitekta.

Bayer bolstered its portfolio of newly launch products via European approval of Xofigo for prostate cancer; the drug was approved in the US earlier this year - see ViewPoints: Combination use beckons for Bayer's newly approved prostate treatment Xofigo say experts, if radioactivity concerns can be overcome.

Health Canada approved Johnson & Johnson's protease inhibitor simeprevir – to be sold as Galexos – for hepatitis C ahead of an imminently expected approval in the US.

Amgen unveiled positive data for its PCSK9 inhibitor evolocumab against the back-drop of a debate as to the commercial opportunity for these products (see above).

Daiichi Sankyo looks set to enter the market for 'next-generation' oral anticoagulant products after the publication of compelling data for its Xa inhibitor edoxaban. However, the Japanese company – which will most likely seek a US marketing partner – may face an uphill task in the face of entrenched competition, namely Bayer's Xarelto (see ViewPoints: Agree to disagree – Bristol-Myers Squibb plays down once-daily dosing of Bayer's Xarelto as Eliquis continues to slow burn.

Sanofi said Monday that it discontinued all clinical trials of fedratinib, previously referred to as SAR302503, and also cancelled plans for regulatory filings of the investigational JAK2 inhibitor. Following a risk-benefit analysis, including consultation with the FDA, Sanofi stated that "the risk to patient safety outweighed the benefit that fedratinib would bring."

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