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

Battle lines continue to be drawn in the immuno-oncology race

The past week has seen a number of events that illustrate the growing influence of immuno-oncology development on the pharmaceutical sector.

Bristol-Myers Squibb confirmed late last week plans to exit early-stage R&D in hepatitis C, diabetes and neurology. The company described the move as a "slight" shift in focus (which will reduce Bristol-Myers Squibb's headcount by just 1 percent), but did suggest that it would allow further investment in its immuno-oncology pipeline.

Some have suggested that Bristol-Myers Squibb go further and exit the diabetes market altogether by selling its portion of the joint venture it operates with AstraZeneca to the UK drugmaker. Funds raised would provide a significant investment opportunity, which could enhance Bristol-Myers Squibb's leadership of the immuno-oncology market. Speculation that the US drugmaker is weighing up this type of strategy may continue for some time, particularly in light of recently announced senior management changes.

For further analysis see In Focus: Bristol-Myers Squibb's R&D shake-up – A tale of two acquisitions and ViewPoints: Talk of diabetes JV split illustrates divergent paths of AstraZeneca, Bristol-Myers Squibb.

The past 12 months have certainly validated this approach to treating cancer, and strategies implemented now could have significant implications over the next few decades if immuno-oncology delivers on its commercial promise. Roche also looked to add another string to its immuno-oncology bow this week by announcing a collaboration with the German biotech immatics (see ViewPoints: Cancer immunotherapy gold rush gathers pace as Roche signs agreement with vaccine player), while AstraZeneca has also made a number of related acquisitions. Merck & Co. investors may be getting jittery; the US pharma giant may need to strike out on its own in-licensing path in order to support its own offerings.

Long-awaited cholesterol management guidelines announced

New guidelines issued on Tuesday by the American Heart Association (AHA) and the American College of Cardiology (ACC) offer a radical change in thinking towards how cholesterol should be managed. How quickly these guidelines are adopted, and what impact they have on the sale of branded products, remains conjecture at this point.
The key conclusion, however, is that the guidelines further cement the role of statin therapy at the heart of cholesterol management, thus potentially raising the barriers-to-entry (or more accurately physician uptake) for new cholesterol-reducing therapies.

An early suggestion is that the AHA and ACC may have delivered a blow to the multi-billion dollar potential of the PCSK9 inhibitor class, but even this outlook is tinged with uncertainty. The new guidelines may mean that uptake of the new therapies is slower until data from outcomes studies are available (expected in 2018).

However, some analysts argue that a potential two-fold increase in the use of statins will simply expose a greater number of patients who are intolerant or fail to respond to this gold-standard treatment. This in turn expands the likely patient population for the PCSK9 inhibitor class.

Confusion surrounds potential Lemtrada approval

Good luck for anyone trying to guess whether the FDA will approve Sanofi's multiple sclerosis treatment Lemtrada. Briefing documents released ahead of Wednesday's advisory committee were among "the most critical I have ever seen," Bloomberg Industries analyst Andrew Berens told FirstWord. The FDA reviewers in particular questioned the design of Genzyme's Phase III study, and specifically its decision to un-blind patients.

Fast forward past the AdCom meeting itself and chances of approval are "certainly better," says Berens, but by no means secured. At the crux of a difficult decision for the FDA is weighing up whether to enforce its view that late-stage studies were not designed as they should have been, against a strong opinion from physicians within the MS community that Lemtrada should be made available. Given that Sanofi's drug is not likely to be used in a large proportion of MS patients – but rather carve out a niche position – approval with a limited label is one potential outcome. Other analysts have suggested, however, that the FDA's stance in the AdCom dictates that the likely outcome is a second complete response letter.

Given the challenges of this submission, a final FDA decision on approving Lemtrada is likely to go "above division and up the food chain," suggests Berens. He also adds that the impact of recent European approval of Lemtrada – with a surprisingly broad label – will have some influence on the FDA's decision making.

Oncologists keen for Gazyva

Having gained rapid approval for its chronic lymphocytic leukaemia (CLL) treatment Gazyva, uptake of Roche's drug is also expected to be rapid, according to oncologists polled by FirstWord at the beginning of the week - see Physician Views Poll Results – Uptake of Roche's Gazyva expected to be rapid; additional data with other chemotherapy regimens will be critical in driving usage, however.

Familiarity with Roche's older Rituxan franchise will act as one barrier to uptake – as will Gazyva's initial approval with a less aggressive form of chemotherapy – but recently published headline data that is to be presented at the forthcoming annual meeting of the American Society of Haematology (ASH) look poised to drive quick penetration in the CLL setting.

Should poll results prove accurate, launch of Gazyva will further validate Roche's strategy to both enhance and defend its leadership of key cancer segments, following the successful launches of Perjeta and Kadcyla in HER2-positive breast cancer.

FDA "shows its teeth" with rapid approval for Pharmacyclics' Imbruvica

Approval of Gazyva came earlier than expected (around seven weeks), but given its advanced nature was not seen as indicative of the increased speed to market bestowed by the FDA's Breakthrough Therapy designation. Approval of Pharmacyclics and Johnson & Johnson‘s Imbruvica (ibrutinib) – for patients with mantle cell lymphoma (MCL) who have received at least one prior therapy – may be more indicative, however.

Analysts at Morgan Stanley suggested that an "aggressive approval timeline" 107 days before Imbruvica's PDUFA date "reveal the FDA’s Breakthrough designation has teeth."

Despite the speediness of approval in MCL, some intrigue surrounds Imbruvica’s progression towards a green-light for relapsing/remitting chronic lymphocytic leukaemia (CLL), with regulatory submission for both indications made under a single new drug application.

A clean label in MCL bodes well for broader approval despite the delay, note analysts, while an early approval for MCL would appear to preclude the FDA’s requirement for any advisory committee, note’s Morgan Stanley’s Yigal Nochomovitz.

One key question is whether the FDA will approval Imbruvica in CLL ahead of (or independent of) interim Phase III data due in January, or whether a request for the results could delay approval. Given that the CLL indication did not have Breakthrough Theray status, the FDA has set a PDUFA date of February 28. Analysts at JP Morgan note that even if data from the RESONATE study did cause the FDA to extend its review of Imbruvica, assuming the results are positive, it would most likely prompt off-label use in CLL prior to approval.

See also ViewPoints: Will the FDA send out message on breakthrough therapy status with speedy approval for Johnson & Johnson, Pharmacyclics' multi-billion dollar candidate ibrutinib?

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