Friday Five – The week in review / 2017 – year of the IDO inhibitor?

2017 – year of the IDO inhibitor?

Focus on IDO inhibitors has been sharpening for some time, and the coming months could see an accumulation of data to suggest this drug class will emerge as an important backbone therapy in the field of immuno-oncology.

This week, the annual meeting of the American Association of Cancer Research (AACR) provided the backdrop for further updates, including disclosure of additional details about a late-stage collaboration between Incyte and Merck & Co., previously confirmed in January – focused on combination studies of Incyte's IDO inhibitor epacadostat and Merck's PD-1 inhibitor Keytruda – and the announcement of an additional late-stage collaboration with Bristol-Myers Squibb (ViewPoints: Incyte plots an agnostic approach into the immuno-oncology big league).

Raising the profile of IDO inhibition in the process, epacadostat has become the first 'second generation' immuno-oncology agent to advance to Phase III studies and with some momentum; across the two collaborations with Merck and Bristol-Myers Squibb, epacadostat will be pushed into at least eight pivotal-stage trials, in combination with either Keytruda or Bristol-Myers Squibb's competing PD-1 inhibitor Opdivo, across six tumour types.

Enthusiasm for this approach has been driven by Phase II data from Incyte and Merck's ECHO-202 study in first-line melanoma, presented at last year's annual meeting of the European Society for Medical Oncology (ESMO); the combination of epacadostat and Keytruda showed comparable efficacy to Bristol-Myers Squibb's pairing of Opdivo and Yervoy (a CTLA-4 inhibitor), but with notably reduced toxicity. A second set of IDO inhibitor Phase II data were presented at this week's AACR meeting for NewLink Genetics' indoximod, also in combination with Keytruda in first-line melanoma. Investors were unimpressed that indoximod failed to quite match the efficacy of epacadostat, with NewLink's share price closing down 10 percent on Tuesday. With a limited amount of data for the class as a whole, however, it may be too premature to draw conclusions (ViewPoints: NewLink data help to validate IDO inhibitor class, but Incyte collaborations have raised the bar).

Focus is actually on the data investors are yet to see; the suggestion being that both Merck and Bristol-Myers Squibb must have seen impressive Phase II results behind closed doors prior to committing to pivotal-stage collaborations with Incyte, particularly as both companies also have internal IDO inhibitors in development (albeit at an earlier stage of study).   

The American Society of Clinical Oncology (ASCO) annual meeting could represent a 'coming out' party for the class if mid-stage data for the various epacadostat/Keytruda cohorts are presented, suggested Bernstein's Tim Anderson this week. Positive data would reaffirm the view – which has gained further credibility this past week – that IDO inhibitors could potentially replace CTLA-4 inhibition as a 'cleaner' combination pairing with PD-(L)1 inhibitors; an outcome that would further shake-up the immuno-oncology landscape.

See also Spotlight On Interview: FirstWord discusses Incyte's long term growth plans with CEO Hervé Hoppenot

 

More pressure on Bristol-Myers Squibb?

Any emergence of the IDO inhibitors as a more favourable drug class to pair with PD-(L)1 inhibition could have profound implications for Bristol-Myers Squibb, which has banked heavily on the success of its Opdivo/Yervoy combination; both as a marketed treatment for melanoma and a development-stage pairing in other tumour types, with Phase III data in non-small-cell lung cancer due to read out in the next 12 months.

Spotlight On: Bristol-Myers Squibb finds few favours at AACR as uncertainty around immuno-oncology outlook persists

At the AACR meeting this week, Bristol-Myers Squibb presented new survival data for the combination of Opdivo and Yervoy in previously untreated advanced melanoma patients, but results proved somewhat inconclusive regarding clinical rationale for use of this pairing instead of Opdivo monotherapy; an issue FirstWord polled oncologists about this week.

 

The low-down on Ocrevus

In response to last week's approval of Roche's Ocrevus – a new treatment for relapsing remitting multiple sclerosis and the first approved therapy for primary progressive forms of the disease – FirstWord snap-polled US neurologists to better understand where this therapeutic will fit into the treatment paradigm (Physician Views Poll Results: Ocrevus set to slot in a second-line, but first-line aspirations in MS remain intact).

Our latest KOL Views interview reinforces the suggestion that Ocrevus will be a disruptive addition to the multiple sclerosis market (KOL Views: Leading neurologist expects Roche’s Ocrevus to make a big splash, with ripples likely being felt by all competing MS drugs).

 

Teva gets there first with Austedo, but what about the competition?

A spate of recent novel drug approvals continued this week with FDA clearance of Teva's Austedo for the treatment of chorea associated with Huntington's disease. Approval comes nearly a year after Austedo's originally scheduled PDUFA date and could play a key role in reviving Teva's growth trajectory as generic erosion of its Copaxone franchise intensifies.

That is if Austedo lives up lofty internal expectations; Teva having paid $3 billion to acquire Auspex Pharmaceuticals and Austedo two years ago, with management previously suggesting the drug could generate peak annual sales of around $2 billion if approval can be expanded into a number of additional indications.

Some analysts are sceptical, pointing to inclusion of a black-box label on Austedo's newly-approved label (warning of its potential for causing depression and suicidality) and the emergence of competitor therapies; specifically Neurocrine Biosciences' Ingrezza, which could be approved later this month (ViewPoints: Teva’s Austedo passes regulatory hurdle but several more loom large).

Those with an interest in Austedo and the Huntington's disease landscape should keep an eye out for our latest KOL Views interview – KOL Views: Teva’s movement disorder drug Austedo approved in US but with a black box – implications for next-gen tetrabenazine tussle?

 

Every little counts for Ibrance

Focus on the CDK4/6 inhibitor class has been recently sharpened on approval of Novartis' second-to-market product Kisqali, but Pfizer's Ibrance secured an important label update late last week, which should help it fend off competition.

In converting Ibrance's approval from an accelerated to regular nod, the FDA also modified its label to include use with any aromatase inhibitor as a therapy for previously untreated HR-positive, HER2-negative breast cancer. Ibrance was previously approved for use only in combination with Novartis' aromatase inhibitor Femara.

Pfizer has previously said that Ibrance's upgrade to full approval, in incorporating results from the Phase III PALOMA-2 trial, will help to drive uptake of the drug in later-adopting oncologists. The company is hopeful that this will build on strong utilisation in early adopters, which has pushed global sales above the $2 billion mark just under two years since launch.

Flexibility on how Ibrance can be prescribed with any aromatase inhibitor will also help matters, and was recently cited by Novartis as one advantage in favour of Kisqali. In response to approval of Novartis' drug FirstWord snap-polled 30 US-based oncologists, 93 percent of whom said use with any aromatase inhibitor was a compelling proposition; 33 percent described this flexibility as 'significantly' compelling and 7 percent as 'extremely' compelling.

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