Friday Five – The week in review

Merck & Co. proves its IO credentials once again

With the immuno-oncology market proving to be anything but predictable, Merck & Co. has shown itself to be the most adept among the front-running players at navigating the landscape. The company has previously achieved success by taking a more measured approach versus rivals and has also shown a willingness to pull surprises out of the hat. FDA approval of Keytruda this week – for combination use with chemotherapy in previously untreated non-small-cell lung cancer (NSCLC) patients, irrespective of PD-L1 status – is the culmination of one such strategy. Merck's decision to file its application on the strength of impressive data from a Phase II trial in January caught all off-guard; its reward is the most commercially significant approval for any immuno-oncology product to date – JP Morgan 2017: Stealing their thunder? – Merck & Co. does it again

Events this week will also fuel speculation that Merck's success in the immuno-oncology market is not driven only by management's strategising. Could Keytruda simply be a better product than other drugs in the PD-1 and PD-L1 inhibitor class? Failure of Roche's Tecentriq to show a survival benefit in second-line bladder cancer patients – where Keytruda has already set a benchmark – represents a second case where Merck's product has outperformed a rival in a pivotal-stage trial –  ViewPoints: Merck & Co. continues to win the key plays in immuno-oncology race

Head scratching at Roche and the FDA

It's difficult to assess Tecentriq's failed pursuit of a survival benefit in previously treated bladder cancer patients without the benefit of full data from Roche's Phase III trial; now likely to be presented at the annual European Society of Medical Oncology (ESMO) meeting in September.

Looking at the broader picture, this indication represents a small slice of the overall immuno-oncology market and Roche has bigger fish to fry. Indeed, management has likely welcomed FDA endorsement of Merck's 'chemo-combo' approach, with Roche prioritising a similar strategy for Tecentriq in first-line NSCLC, data for which is expected to readout later this year.

The FDA too finds itself in a pickle, having granted accelerated approval to Tecentriq and three other PD-(L)1 inhibitors in second-line bladder cancer on the strength of tumour response rates and duration of response data. The only drug in the class yet to be approved in this indication is the only one to have demonstrated a survival benefit – Keytruda. Merck wins again – ViewPoints: Roche throws an immuno-oncology curveball as the FDA is left to ponder what it does next

Hikma's setback casts a warm glow on Teva's AirDuo strategy   

Teva's recent decision to launch two versions of its AirDuo product in the US market looks like an increasingly smart one. Both products, one of which is an in-house authorised generic, will compete as non-substitutable competitors to GlaxoSmithKline's blockbuster asthma and chronic obstructive pulmonary disease (COPD) treatment Advair Diskus – ViewPoints: A generic by any other name – will stakeholders buy in on Teva’s kinda sorta generic equivalent to Advair?

Following prior speculation, Hikma Pharmaceuticals announced on Thursday that it has received a complete response letter from the FDA for its AB-rated generic Advair product and suggested there is a low-likelihood the product will be approved this year. GlaxoSmithKline's flagship product will not face true generic competition in the US market until 2018 at the earliest it seems.

The primary beneficiary of this delay is new GlaxoSmithKline CEO Emma Walmsley, who gains some breathing space in terms of financial performance over the remainder of 2017. That said, in the short term, Walmsley is likely to be judged primarily on the strategic outlook she unveils for GlaxoSmithKline in the summer; the company's commitment to asthma and COPD remains intact and could prove to be sustainable revenue stream. What it lacks, however, is high-level innovation. 

Physician Views Poll Results: Teva's authorised generic AirDuo strategy looks set to deliver a material impact in asthma market

KOL Views: Leading pulmonologist sees Teva’s AirDuo as a legitimate threat to GlaxoSmithKline’s Advair and other ICS/LABA combos

What about the respiratory biologics?   

GlaxoSmithKline and a handful of other players are seeking to innovate in the respiratory market through the development of biologic therapies for more severe forms of asthma and COPD; indeed both GlaxoSmithKline and Teva can boast recent approvals in the asthma market for their respective IL-5 antagonist monoclonal antibodies Nucala and Cinqair.

Further question marks over a competing class of biologic have been raised this week, however, by AstraZeneca's announcement that its IL-13 antagonist tralokinumab failed to achieve its primary endpoint in the first of two Phase III trials. This setback follows mixed data last year for Roche's IL-13 lebrikizumab; a drug since abandoned by the Swiss player. Future approvability of tralokinumab will now be dependent on efficacy in patients with specific biomarkers; a justifiable approach agree key opinion leaders, albeit one that could significantly curtail the commercial opportunity of AstraZeneca's product – ViewPoints: Following AstraZeneca's tralokinumab setback, are IL-13 inhibitors in the last chance saloon?

GlaxoSmithKline was also dealt a blow this week in its efforts to expand approval of Nucala into severe COPD patients. Preliminary data from two pivotal-stage trials showed Nucala had met the primary endpoint of a significant reduction in moderate to severe exacerbations in one study, but failed in the other. The results endorse a view among experts that the IL-5 class is likely to be less effective in COPD versus asthma patients.

A familiar foe to CAR-T development, but Kite should keep sailing says expert    

Just when the CAR-T story was ticking along nicely – on the back of both Novartis and Kite Pharma successfully submitting their first products to the FDA – the latter confirmed this week the death of a non-Hodgkin's lymphoma patient from cerebral oedema who was treated with Kite's KTE-C19 in the pivotal Phase II ZUMA-1 trial.

Prior to this week there had been no reported deaths in patients treated with Kite's CAR-T product attributed to cerebral oedema. Onset of this condition has been at the forefront of investors' minds when it comes to CD19-directed CAR-T cell therapies, given it was the cause of a handful of deaths in a study of Juno Therapeutics' JCAR015, ultimately causing the company to shelve that programme late last year.

Thus, a fatal case of cerebral oedema tied to KTE-CD19 – which like JCAR015 was designed using a similar CD28-based co-stimulatory domain to boost T-cell response – inevitably set off alarm bells in the minds of many investors.

Marco Davila, an associate member at the Moffitt Cancer Center and physician-scientist who has been a clinical investigator on trials involving CAR-T therapies, told FirstWord that he does not believe the death will derail KTE-CD19's bid for approval, though the FDA may choose to be more conservative about the population for which the agent would be indicated – ViewPoints: KOL weighs in on impact of patient death on prospects for Kite Pharma’s KTE-C19

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