FirstWord Lists – Five key products in AstraZeneca's pipeline – can they deliver?

Pfizer's month-long pursuit of AstraZeneca has provided the backdrop to an earlier than expected 'R&D turnaround' narrative at the UK drugmaker. This story has continued to gain notable momentum over the past two weeks, as AstraZeneca has released a series of new data disclosures for mid- and late-stage pipeline compounds.

Bullish revenue forecasts have in part been shaped by the defensive posturing of AstraZeneca's senior management, but also appear to represent a shift in the company's internal R&D dynamics. Nevertheless, there remains some doubt as to whether the company can deliver on its aggressive targets; former head of R&D at Pfizer John LaMattina recently suggested that proposed organic growth of 75 percent over the next decade – largely driven by the pipeline – would represent a "remarkable" feat.

Analysts, however, are becoming increasingly comfortable with AstraZeneca's pipeline story. UBS' Alexandra Hauber wrote this week that "consensus looks increasingly outdated, as many market competitors may be restricted or are simply too slow to keep up with AstraZeneca's pace." The key for AstraZeneca now is to retain this momentum; not only to reinforce the view that its R&D turnaround is material, but to insulate against any weakness in its share price that could trigger a second opportunistic approach from Pfizer.

FirstWord takes a look at five pipeline products that AstraZeneca hopes will play a key role in its next stage of evolution...

MEDI4736

AstraZeneca's PD-L1 antibody is arguably the jewel in the crown of its pipeline and provides the company an opportunity to compete in the first generation of checkpoint inhibitor immuno-oncology (IO) products.

AstraZeneca's own non-risk adjusted peak sales for MEDI4736 are $6.5 billion, but the company remains behind Bristol-Myers Squibb, Merck & Co. and Roche in the development race. Whether all of these players can 'win' remains a moot point, meaning that the key question for AstraZeneca is how it can differentiate MEDI4736 from competing products?

A point of differentiation, argues the company, is the potential for MEDI4736 to become the first PD-1/PD-L1 antibody to be approved for stage III non-small-cell lung cancer (NSCLC) in patients who have undergone chemotherapy. This indication represents a peak $2 billion opportunity alone, adds Hauber, although she concedes that any of the other IO players could quickly follow AstraZeneca's lead with the PACIFIC study.

Tremelimumab

In detailing the commercial opportunity for MEDI4736, AstraZeneca CEO Pascal Soriot was at pains to stress that the company's $6.5 billion peak forecast encompasses the all-important combination opportunities that are expected to play a pivotal role in shaping the usage of PD-1/PD-L1 products.

According to some analysts, partially offsetting AstraZeneca's earlier-stage pipeline in IO is the breadth of checkpoint inhibitors that have rapidly emerged in early-stage clinical testing, with a particular focus on tremelimumab.

The drug – somewhat ironically in-licensed from Pfizer – is only the second anti-CTLA4 antibody in clinical testing (the other being Bristol-Myers Squibb's Yervoy, which is approved for the treatment of melanoma and is being tested in a range of other tumours as a combination agent).

The thesis that anti-CTLA4 products could emerge as 'backbone' therapies in IO has lost some of its appeal in recent months owing to weaker than expected data presented by Bristol-Myers Squibb in lung cancer. That said, the jury is very much still out and tremelimumab offers AstraZeneca a combination opportunity that Merck and Roche don't have.

AZD9291

The progression of AZD9291 into late-stage testing, through to regulators and subsequently into the commercial arena is expected to occur rapidly over the next 12-18 months. The irreversible EGFR-targeting tyrosine kinase inhibitor – designed essentially to treat those NSCLC patients who develop resistance to current EGFR inhibitors – is cast in a David and Goliath story with AstraZeneca's key competitor being Clovis Oncology, a much smaller biotech company who is developing CO-1686.

Both products have been granted breakthrough therapy status by the FDA, but it is with AZD9291 where AstraZeneca has shown tangible acceleration of its development efforts to close the gap with Clovis. Analysts are cautious towards a small number of interstitial lung disease cases in AstraZeneca's ASCO abstracts for AZD9291, which they suggest may provide Clovis a slight edge in terms of overall clinical profile. Full ASCO data and the speed at which AstraZeneca can push the drug towards regulators appears critical to its chances of success at this stage.

Combination diabetes product (SGLT-2/DPP-4)

AstraZeneca may have become a fully fledged diabetes player by virtue of buying out Bristol-Myers Squibb from its previously operated joint venture, but its credentials in the market – certainly as a pace-setter – remain unproven.

A recent disclosure illustrates, however, that AstraZeneca could potentially be the first player to deliver the combination of a SGLT-2 inhibitor and DPP-4 inhibitor (dapagliflozin and saxagliptin) to the market. With the company inferring that regulatory filing could occur by the end of the year, AstraZeneca appears to have leapfrogged Eli Lilly and Boehringer Ingelheim in this particular race.

Recently disclosed top-line data for the dapagliflozin/saxagliptin combination would appear to demonstrate comparable efficacy to Novo Nordisk's Victoza, but offer the added convenience of oral dosing. Thus a key disclosure to watch will be weight-loss data to be presented at next month's ADA meeting (June 13-17).

Benralizumab

One of the more interesting opportunities for AstraZeneca is in the respiratory space, where its long-established Symbicort franchise is currently enjoying something of a renaissance in the US market.

"While we believe (AstraZeneca's) $8 billion peak revenue estimate for overall respiratory sales may be optimistic given the sluggish launch of GSK's Breo [Ellipta] and competition within the LAMA/LABA and LAMA/LABA/ICS area, we continue to believe AstraZeneca's respiratory biologics franchise is widely underappreciated," suggests Leerink Swann analyst Seamus Fernandez.

One such product – the anti IL-5R antibody benralizumab, which is being developed for the treatment of severe asthma – is a potential $2 billion per-year drug, argues the company. Investors will have to wait some time to see if this prediction has substance, with Phase III data due to be published in 2016. Analysts at Bloomberg Industries have pointed out, however, that data from the recent American Thoracic Society (ATS) meeting is shaping a strong profile for the product; not only is the compound being developed with a "significantly differentiated" eight-week dosing schedule (versus monthly dosing for key rivals), but benralizumab "depletes offending immune cells rather than simply inhibiting their activation," potentially providing it a best-in-class profile.

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