Friday Five – The week in review / FDA approvals continue apace

A busy FDA

In approving Neurocrine Biosciences' Ingrezza as the first available treatment for tardive dyskinesia this week, the FDA racked up its 14th novel drug approval of 2017. While it would be erroneous to extrapolate this approval rate over the remaining 7.5 months of the year, it is worth noting the agency approved just 22 NDAs in 2016; the catalyst of some debate centred around pharma's R&D productivity. Furthermore, approval of Eli Lilly's rheumatoid arthritis treatment Olumiant appears imminent.

FDA approvals in 2017 to date also encompass more than a handful of potential blockbuster drugs, including Roche's Ocrevus (multiple sclerosis) and Regeneron Pharmaceuticals and Sanofi's Dupixent (atopic dermatitis), an additional entrant to the PD-(L)1 class in Pfizer and Merck KGaA's Bavencio and important oncology approvals in other classes – Novartis' Kisqali, a CDK4/6 inhibitor for breast cancer, and Tesaro's PARP inhibitor Zejula for ovarian cancer.

Pending NDAs expected to subsequently achieve blockbuster status include AstraZeneca's PD-L1 inhibitor durvalumab and Novo Nordisk's GLP-1 agonist semaglutide. 


Ingrezza versus Austedo

Positive regulatory outcome for Ingrezza comes hot on the heels of FDA approval for Teva's Austedo, also a VMAT2 inhibitor, which was cleared for the treatment of chorea associated with Huntington's disease last week. While Neurocrine is not developing Ingrezza for this indication, Austedo has an August PDUFA date in the much larger tardive dyskinesia indication, where these two drugs will compete directly.

Ahead of Austedo's potential approval in tardive dyskinesia, Neurocrine appears to hold a considerable advantage: the lack of a black-box warning on Ingrezza's label. Whether Austedo's warning is warranted or not – this key opinion leader (KOL) expressed disappointment at the language used by the FDA – the commercial implications could be significant – ViewPoints: Ingrezza's label puts Neurocrine in the driver’s seat in movement disorders.


Keytruda versus Opdivo

Johnson & Johnson kicks of pharma's first-quarter earnings season next week, where one of the most keenly watched metrics will be the respective growth performances for Merck & Co.'s Keytruda and Bristol-Myers Squibb's Opdivo; a pair of competing PD-1 inhibitors both approved for the treatment of non-small-cell lung cancer, albeit with one critical difference – late last year Keytruda became the first and only PD-1 to be approved in first-line patients.

Our latest Physician Views snap poll seeks further clarity on utilisation dynamics of both products in NSCLC before first-quarter earnings season hits its stride in the next few weeks.

On a more positive note for Bristol-Myers Squibb, feedback from a leading oncology KOL indicates that new data presented by the company at the recent American Association for Cancer Research (AACR) annual meeting regarding combination use of Opdivo/Yervoy for the treatment of first-line melanoma is unlikely to significantly change prescribing habits. While not powered to compare use of this combination to Opdivo monotherapy, the latter demonstrated a competitive survival benefit with much lower toxicity.


Axovant's coup   

Axovant Sciences on Monday announced that former Medivation chief executive and founder David Hung has been selected as its next CEO effective April 7, sending the company's shares up as much as 28 percent.

It is unusual for a new CEO to cause a massive swing in market cap one way or the other, but once again Axovant has proven it is no ordinary biotech. The company wasted no time in monetising the sudden outburst of bullishness, pulling the trigger on a $100-million financing, though what exactly is driving investor sentiment is a little unclear. 

Some speculators are no doubt hoping that his success as a dealmaker – credentials burnished by a big-money licensing deal (in Alzheimer's disease no less) with Pfizer in 2008, even prior to the recent acquisition of Medivation by Pfizer – could translate into a near-term takeout if Axovant's intepirdine finds the mark in MINDSET.

At the same time though, Hung has also experienced success in building a commercial organisation from scratch, which he helped do after Medivation found success with Xtandi (enzalutamide), a prostate cancer drug that the company built into a blockbuster – albeit with the assistance of co-marketing partner Astellas. Indeed, media reports indicate that Hung has no interest in finding a buyer for Axovant, and is instead joining for the long haul.

This latter outcome would be more in keeping with the long-term plan outlined to FirstWord by former Axovant CEO Vivek Ramaswamy earlier when he suggested that the goal is to use intepirdine's success to help build the company into a fully integrated, global commercial organisation (JP Morgan 2017: Axovant's awe-inspiring ascendency faces year of reckoning in 2017, acknowledges CEO Vivek Ramaswamy).

Then again, as any skilled negotiator would recognise, Hung and Ramaswamy have nothing to gain from acknowledging an interest in selling Axovant at this point, and instead would simply be giving away some of their bargaining leverage.


OncoMed – down but not out?

OncoMed Pharmaceuticals is hopeful it can re-partner a pair of cancer stem cell (CSC)-targeting programmes that Bayer decided to return this week, but a simultaneous clinical disappointment with a separate compound from the same platform may complicate this endeavour.

It was not long ago that technologies designed to target CSCs to short-circuit a tumour's ability to metastasise and develop resistance was one of the hottest arenas in oncology, and OncoMed was one of the hottest names in it thanks in no small measure to the validation of big-money partnerships with the likes of BayerCelgene and GlaxoSmithKline.

This week, OncoMed announced that Bayer will not exercise its option to license a pair of "Phase II-ready" Wnt pathway inhibitors that have been evaluated in a variety of solid tumour settings. Vantictumab has completed Phase Ib trials in breast and pancreatic cancer, while ipafricept has been tested in ovarian and pancreatic cancer.

Paul Hastings, CEO of OncoMed, noted that Bayer cited "strategic reasons" for returning the programmes, and the decision was not related to any untoward signals observed with the agents. For all their promise though, OncoMed’s anti-CSC compounds have consistently underwhelmed in human testing thus far, which could make finding a new home for vantictumab and/or ipafricept more difficult. Among the many questions that will inevitably be asked in the wake of OncoMed’s latest disappointment is whether the problem is its choice of indications or the CSC platform itself – ViewPoints: Double whammy for OncoMed calls CSC platform into question.

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