Friday Five – Your weekly pharma review

Novo Nordisk and Sanofi poised to open a new competitive front in diabetes

Two new types of diabetes medication – therapies developed by Novo Nordisk and Sanofi which combine a GLP-1 agonist with basal insulin – were assessed by an FDA advisory committee this week and look well positioned for US approval in the near future. Novo Nordisk's IDegLira received a unanimous recommendation for approval, while Sanofi's IGlarLixi fared nearly as well, with panellists voting 12-2 in favour.

Briefing documents published by the FDA ahead of the AdCom meeting never looked set to preclude approval of either drug but do raise questions pertinent to the commercial performance of IDegLira and IGlarLixi; specifically whether improved convenience compensates for less flexible dosing – a questioned echoed by diabetes key opinion leaders interviewed by FirstWord.

We will be speaking to an expert next week for an in-depth discussion regarding this week's AdCom assessment and how these drugs are likely to be used assuming the FDA follows panellist recommendations for approval.

Key biosimilar applications made in Europe and the US

Notable biosimilar applications were confirmed on both sides of the pond this week. Novartis' Sandoz division confirmed that its biosimilar version of rituximab (Rituxan) has been accepted for review by the European Medicines Agency and Samsung Bioepis confirmed its application for the biosimilar infliximab (Remicade) product SB2 has been accepted by the FDA.

Novartis' application arguably ups the pressure – albeit incrementally – on originator company Roche. Although Celltrion became the first player to submit a biosimilar rituximab product to the EMA last November, it is reported that Novartis' product is supported by a broader set of clinical data. While both products may gain approval, strength of clinical evidence is likely to be critical in driving adoption of biosimilar antibody products among oncologists.

In the US, the FDA has already approved its first biosimilar infliximab product, although it remains unclear when Inflectra – developed by Celltrion, to be marketed by Pfizer – will launch. Samsung's application provides the first tangible evidence that competition in the biosimilar infliximab market may not be too far away once intellectual property hurdles are overcome. Furthermore it enhances a growing reputation for Samsung in the biosimilars space, following approval and launch of its biosimilar etanercept (Enbrel) product Benepali in Europe earlier this year.


Spotlight On: Biosimilar Enbrel adopted rapidly in Norway; can Europe's pacesetter share its positive experience with other countries?


All eyes on Entresto  

The slower than expected launch for Novartis' heart failure drug Entresto has been scrutinised repeatedly in recent months but the Swiss company received a significant boost this week with both European Society of Cardiology (ESC) and the American College of Cardiology (ACC) publishing updated guidelines which recommend using Entresto in patients receiving stable therapy with ACE inhibitors/ARBs.

Anticipation for US guidelines was particularly pronounced given the slower launch of Entresto in this market versus Europe. The ACC did not disappoint, delivering a stronger-than-expected recommendation in favour of Entresto which has also been published ahead of schedule; Novartis had guided towards publication of new guidelines in the fourth quarter.


FirstWord has polled US-based cardiologists and primary care practitioners to ascertain what impact these new guidelines are likely to have on adoption of Entresto - 


Exelixis throws spotlight on renal cell carcinoma opportunity

Medivation currently remains biotech's preeminent acquisition target; Sanofi this week nominated eight individuals to replace the company’s current board while rumours intensified around potential counter bids from Celgene and Gilead. A host of other large-cap pharma and biotech companies have been linked to Medivation.

One question posed this week was whether Exelixis could emerge as another takeout candidate in the coming weeks and months. The company recently gained approval for Cabometyx as a second-line treatment for renal cell carcinoma, and feedback from oncologists polled by FirstWord suggests that Exelixis' drug could prove a viable competitor to Bristol-Myers Squibb's Opdivo in this indication.


Physician Views Poll Results: Exelixis' Cabometyx could prove David to Opdivo's Goliath in renal cell carcinoma, say oncologists


This week, the company unveiled encouraging data for Cabometyx in first-line patients, beating the current standard of care (Pfizer's Sutent) when measured by progression free survival (PFS). Some analysts suggested this could double or triple the commercial opportunity for Cabometyx but Exelixis shareholders appear to be remaining cautious.

The competitive threat of Opdivo will likely overshadow the launch of Cabometyx, one investment manager told FirstWord, while the EU-licensing deal Exelixis signed with Ipsen in harder times may limit interest in the company from European-based Big Pharma, he adds. That said, Astellas' co-ownership of Xtandi has not prevented much interest in Medivation.

We will be discussing Cabometyx' PFS data in first-line RCC patients and the potential opportunity in this indication with an expert on Friday (May 27).

Is the FDA digging itself into an eteplirsen-shaped hole?

The FDA will likely face criticism whether it approved Sarepta Therapeutics' Duchenne muscular dystrophy treatment eteplirsen or not. By delaying its decision, the agency is almost certain to put itself under more scrutiny.

On Wednesday, Sarepta announced that the FDA wouldn't complete its review of the drug in time for the scheduled May 26 PDUFA date. With no new date set, Sarepta's shares jumped as much as 24 percent in response; investors appear to echo the view that if the FDA had decided to issue a complete response letter it presumably would have done so already.

It doesn't appear likely, however, that the FDA will approve eteplirsen any time soon. Most analysts concluded that although the FDA is likely considering various options which could ensure patient access to the drug, a CRL remains the most likely outcome.

Some evidence to this effect is provided by the negative tone of FDA briefing documents which were published ahead of the recent advisory committee meeting to discuss eteplirsen. These were critical of limitations in the clinical data submitted by Sarepta.

Set against the tone of these documents, subsequent approval of eteplirsen – and to some extent the extended review the FDA has granted itself – could be viewed as evidence that the agency was swayed, at least partially, by pressure from patient advocates and members of congress in making its decision. This, coupled with the very small 12-patient data set submitted by Sarepta to support approval, sits at the heart of the controversy.

RBC Capital Markets analyst Simos Simeonidis speculates that the FDA has bowed to political pressure in extending its review of the drug. If the agency is seen to have swayed from basing its decision on purely scientific grounds it could set a troublesome precedent. The FDA is not making life any easier; Simeonidis believes the delay will allow advocates to exert additional pressure.

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