Alert - UpdatesPlus-IBD: NICE draft guidance recommending against NHS reimbursement of TNF inhibitors use in ulcerative colitis highlights the case for price reductions or tailored dosing

NICE issues draft guidance recommending against NHS reimbursement of Remicade, Simponi and Humira for patients with ulcerative colitis [link]

• NICE has concluded that none of the TNFis currently approved for ulcerative colitis have been proven to be more cost effective than currently available treatments including corticosteroids and mercaptopurine or azathioprine

• Of interest it was concluded that network meta-analysis did not allow a conclusion to be drawn on the relative effectiveness of the 3 TNF products under evaluation

• The draft guidance has been issued despite NICE acceptance that both disease symptoms and the AEs of steroid treatment significantly diminish QoL, and that TNFis may offer long term remission or at least a bridge to eventual surgery

• Two clinical issues that may have influenced NICE's decision were the lack of rigid guidance on treatment discontinuation in cases of modest responses and of predictors of responsiveness

• The preliminary recommendations are now available for public consultation until Oct 15. Comments received during this consultation will be considered when producing the final guidance, expected in Jan 2015

Comments:  NICE's draft guidance underlines the need for individualized therapy, including greater clinical guidance on when/how to stop or intensify treatment in cases of failure to respond or when a response is achieved.  As highlighted in our previous issue of UpdatesPlus-IBD, Abbvie is investigating a tailored therapy approach although data will not be available until around 2016.  Also of note is a UK post-marketing study opened by Merck earlier this year.  This will allow an analysis of efficacy and healthcare costs associated with Simponi however it seems unlikely that data will be available in time for the final NICE guidance.  Taking these points into consideration, the arrival of biosimilar infliximab in the UK, possibly as soon as next year could be a landmark moment for UK ulcerative colitis patients.  In the next issue of UpdatesPlus-IBD we will look at the guidance in greater detail and attempts to model the price reduction that biosimilar companies may need to target.  In addition we will consider the potential impact of the draft guidance on discounting to the NHS.  Likewise, we will be seeking further clarity at the upcoming European Gastroenterology Week on the potential impact of NICE guidance.  Each of these issues are important from both the point of view of pharma revenues and public health expenditure of the NHS.  It is estimated that 25,000 ulcerative colitis patients are living with severe disease within the NHS.  Of these approximately 50% will have one relapse/year (NICE figures), therefore costing the NHS upwards of £0.4B ($0.65B) each year (based on the an induction therapy cost with Remicade of £5035 and monthly maintenance therapy costs of £839.24*)

This alert is part of Pharma Information & Report's UpdatesPlus-IBD service.  If you do not receive our alerts and reports on a regular basis and wish to do so, or for further information on how to get our coverage of  European Gastroenterology Week please contact fiona.watts@leaddiscovery.co.uk

*Note that this figure is being verified as it is higher than calculated by NICE

Celgene has announced FDA approval of Otezla (apremilast) for the treatment of psoriasis -

This alert is from our UpdatesPlus-Psoriasis and UpdatesPlus-Spondyloarthopathies.  To get more alerts like this and our full monthly reports highlighting and analyzing all key advances in the area please contact fiona.watts@leaddiscovery.co.uk

• Otezla (apremilast) was first approved for the treatment of psoriatic arthritis in March 2014

• The label modification is "Patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy"

• Approval was based on ESTEEM 1 and ESTEEM 2 demonstrating efficacy in treatment-naïve and -experienced patients including those previously treated with biologic agents or conventional systemic agents

• The revised label reports publicly (we believe for the first time) rates of depression

• During the 16wk blinded period of the ESTEEM studies 1.3% (12/920) of subjects treated with Otezla reported depression compared to 0.4% (2/506) treated with placebo.

Comments:  Otezla produced PASI-75 rates of 29-33% over 16wks in the ESTEEM program with an excellent safety profile.  Safety and freedom from monitoring would be expected to drive uptake early in the psoriasis treatment paradigm despite the relatively low efficacy in the context of new biologics.  Of note however, although efficacy is modest, PASI improvement is highly durable over 52wks (data presented at ADD), suggesting those patients who respond well to Otezla can expect to remain on treatment for an extended period.  As mentioned above, the revised label describes rates of depression.  Depression has already been flagged as a potential AE of Otezla at the time of approval for psoriatic arthritis.  In the PALACE studies however, the rates of depression appear similar between control and Otezla treated patients (1% vs 0.8%), and we interpreted the label warning of depression as being class related (roflumilast, another PDE4i is associated with increased depression).  According to the revised label, the increase in depression rates was larger in psoriasis studies (1.3% vs 0.4%).  It is unclear if this is significant.  More importantly, the rates of severe depression; discontinuation due to depression or; of suicidality were very low across treatment groups.  Against this it should be considered that depression is a co-morbidity of psoriasis and it will be interesting to see in real world studies whether depression is worsened in patients with pre-existent depression when receiving Otezla.  One final word; the new indication should help drive Otezla uptake significantly.  In our most recent issue of UpdatesPlus-Spondyloathropathies, we comment on excellent early uptake for psoriatic arthritis with Celgene claiming that Otezla was tying with Humira for the leading new to treatment choice after DMARDs. This represents a 20% share of this cohort.  Celgene has not yet been able to message skin data as the FDA requires specific psoriasis studies for this.  With the new approval however, Celgene reps will not only be able to more easily approach dermatologists, they will also be able to message skin data to rheumatologists further driving uptake in patients with psoriatic arthritis.

Sun Pharma licenses Phase 3 psoriasis candidate, tildrakizumab from Merck

More analysis like this?  Ask us about UpdatesPlus-Psoriasis

• Merck has licensed global rights on anti-IL-23p19 mAb tildrakizumab (MK-3222) to Mumbai-based Sun Pharma for an upfront fee of $80M

• The license is for all indications, although development to date has been limited to psoriasis.  Two Phase 3 studies are currently closed for enrollment and due to reach their primary endpoint Q2 2015

• Merck will continue all clinical development and regulatory activities, but this will be funded by Sun

• Once approved, Sun will be responsible for all regulatory, manufacturing and commercial activities

• Merck is eligible to receive milestone payments and mid-single-digit to teen royalties on commercial sales.

Comments:  Merck published 16wk tildrakizumab data in 2013.  More recent data presented at AAD described long term data with q12w dosing.  Impressively, efficacy was maintained for at least 20wks following discontinuation at 52wks.  This suggest that treatment holidays or reduced dosing frequency may be possible.  Merck indicated in its press release that  today's decision reflects a central strategy to focus it's commercial and R&D activities.  Indeed outlicensing tildrakizumab along with little obvious activity in terms of defending Remicade against biosimilars in effect takes the company out of immunology.  In exception, two developmental candidates remain in respiratory disease.  Sun Pharma indicated that the deal is a part of a strategy of pipeline growth, especially in dermatology.  Sun Pharma is primarily positioned as a generics company, and indeed with the proposed acquisition of Ranbaxy, will consolidate itself as the 5th largest global specialty generic pharma company and the leader in generic dermatology.  This therefore raises questions on the positioning of tildrakizumab.  With the high efficacy of IL-17 mAbs and their likely earlier market entry, Sun Pharma may be intending to eventually launch Tildrakizumab as a more affordable option in both developed and emerging markets. Of note Sun Pharma, along with its subsidiaries, currently has a large network of FDA approved manufacturing sites including those outside of the US which could be leveraged to drive down cost. This in turn would impact not only the IL-17 class but also other IL23mAbs.  Janssen and Boehringer are both developing this class.  Indeed, Janssen reported excellent Guselkumab (CNTO-1959) efficacy from the Phase 2b X-PLORE study at AAD earlier this year and Phase 3 studies have now been announced

The approach of new steroid options for ulcerative colitis

Salix gains tentative approval on Uceris foam [link]

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This content is from our UpdatesPlus-IBD service.  To access our September issue, offering 79 slides of monitoring and analysis of key research and development advances over the past weeks in inflammatory bowel disease please contact us - We cover Ulcerative Colitis and Crohn disease, biologics, orals and topicals, and also supportive care for anemia.  

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• As mentioned in the September issue of UpdatesPlus-IBD, the PDUFA date for Uceris (budesonide) rectal foam for ulcerative colitis was yesterday

• Salix has now announced that the FDA has granted tentative approval

• The oral formulation of Uceris was launched Feb 2013 and most recent quarterly sales were $42.5M

• The oral formulation allows treatment of distal disease as it is formulated in a gastro-resistant tablet which forms a hydrogel in the colon, providing extended release of budesonide in a time-dependent manner.

• The rectal foam is also designed for improved access, allowing exposure extending up to 40cm from the anal verge.   Retention is greater than with current enema formulations and distribution improved compared to suppositories.  Efficacy was reported from 2 pivotal studies in 2013

• The tentative approval reflects outstanding patent issues. which Salix anticipates will be resolved by Q4 2014 allowing Q1 2015 launch

Comments:  The outstanding patent issues relate to AstraZeneca's patent covering Entocort enteric coated budesonide capsules.  Salix does not believe Uceris Foam infringes AstraZeneca's patent however AstraZeneca has a 45-day period for filing suit.  Once this period has expired the FDA will then be able to approve Uceris foam

Biosimilars in immunology...the march continues...Plus coverage of European Gastroenterology Week

Epirus' Remicade biosimilar, BOW015 has received final approval in India [link]

• This marks the first infliximab biosimilar to be approved in India

• Ranbaxy and Epirus signed a licensing agreement for BOW015 in January 2014. Under the terms of the agreement, Epirus was to develop and supply BOW015, while Ranbaxy was to register and commercialize BOW015 in India 

• BOW015 will be manufactured by Reliance Life Sciences in Mumbai and launched as Infimab by Q1 2015

• We understand that the Indian market for Remicade is worth $8-10M/year

• Epirus reported Phase 3 data for BOW-015 in RA patients at EULAR 2014.  In addition to supporting approval in India, Epirus has commented that it intends to leverage clinical data to support additional regulatory filings in targeted global markets

• Ranbaxy aims to launch in other territories in Southeast Asia, North Africa, and selected other markets, while Epirus has previously announced an agreement with Brazilian companies Orygen, Eurofarma and Biolab to support filing in Brazil

• Epirus has commented that it plans to initiate an additional Phase 3 trial in Europe in early 2015

For a detailed look into what's new in the world of biosimilars ask about our UpdatesPlus service.  This dedicated service provides regular monitoring and analysis of immunology therapy areas.

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Special announcement: Attendance of UEG Week (October, 2014)

UEG is the largest gastroenterology meeting in Europe attracting around 14,000 participants.  If you are already active in IBD drug development, or if you are considering expanding into this therapy area, we are offering cost-effective coverage of the meeting.  If you are interested in receiving coverage of the meeting please let us know by the end of this week.  As part of our coverage we would provide the following

• Pre-conference planner with an analysis of what can be expected from key data releases

• Post conference report

• Analysis of key posters and oral presentations

• Update on any new therapeutic candidates approaching the clinic as well as new data on current candidates

• KOL opinion - at the moment key issues will probably be around early Entyvio uptake; attitudes to biosimilar attitudes; opinion around new tailored dosing regimens.  Really however, this is your opportunity to ask us to address any burning questions you may have

To date interest in UEG has been high as by sharing the cost we are able to cover the meeting for a fraction of what is otherwise possible.  So if you are unable to attend but want to know what is to be presented, or if you already have coverage but want a very cost-effective extra pair of eyes and ears please let us know

Kind Consumer gains MHRA authorisation for Voke® Inhaler as an inhaled nicotine formulation to be used as a smoking reduction or cessation aid

The alert below is now part of our UpdatesPlus-Addictive Disorders service.  The intention is to provide rapid alerts of what we consider to be important research and development events across the addictive disorders spectrum from smoking cessation to alcohol abuse.  The content of our alerts are covered in greater detail in our full monthly reports

For full access to UpdatesPlus please contact fiona.watts@leaddiscovery.co.uk

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Kind Consumer gains MHRA authorisation for Voke® Inhaler as an inhaled nicotine formulation to be used as a smoking reduction or cessation aid [Link]

• Kind Consumer has announced receipt of a product license from the UK regulator, MHRA for its nicotine inhaler (Voke® Inhaler 0.45mg)

• The company now intends to submit a variation to the license to support full-scale commercialization by Nicoventures

• Voke® is licensed for use "to relieve and/or prevent craving and nicotine withdrawal symptoms associated with tobacco dependence and to aid smokers wishing to quit or reduce prior to quitting, to assist smokers who are unwilling or unable to smoke, and as a safer alternative to smoking for smokers and those around them"

• The MAA included PK data comparing  Voke® with GSK's Nicorette inhalator

• These data have recently been reported and demonstrate higher early AUC and shorter Tmax with Voke®, as well as reduced craving

Comments:  Voke® is not an e-cigarette - the main differences are summarized below [source], and has beaten e-cigarettes to gain regulatory authorisation for smoking reduction/cessation.  This product is more similar to GSK's Nicorette Inhalator which has been approved for this indication, but with some key differences.  Voke® has been designed to better mimic the look and feel of a cigarette.  Perhaps importantly is the improved nicotine delivery system.  Voke® is a pressure based system, charged from a pressurized can.  The Nicorette inhalator is instead a passive device requiring air to be drawn over wadding containing a nicotine solution resulting in predominantly oromucosal absorption of nicotine in the gaseous state. Instead, Voke® produces a fine aerosol of a medicinal nicotine formulation for inhalation via a breath actuated valve. This is reflected in the distinct absorption profile suggestive of pulmonary absorption. This has two advantages, firstly very little nicotine is exhaled, mitigating regulatory concerns of passive exposure.  Moreover, the improved PK profile is important as slow absorption vs conventional cigarettes has been suggested to limit craving reduction with earlier nicotine replacement products.  This is reflected in the improved reduction of craving with Voke® vs Nicorette Inhalator.  One point of interest is that the device could also be developed for delivery of other inhaled pharmaceuticals. Of note Nicoventures,   Kind Consumer's commercial partner is as an independent company within the BAT group dedicated to smoking alternatives, distinct from nicotine formulations such as patches, gums and e-cigarettes. Nicoventures announced its UK launch in 2011.

Breaking research in ulcerative colitis and Crohn disease

The September issue of UpdatesPlus-IBD is now available offering 79 slides of monitoring and analysis of key research and development advances over the past weeks in inflammatory bowel disease.  We cover Ulcerative Colitis and Crohn disease, biologics, orals and topicals, and also supportive care for anemia.  

For access to this report please contact fiona.watts@leaddisovery.co.uk

Selected items from this issue include:

• Q2 sales/commercial summary for approved biologic and non-biologic therapies including analysis of life cycle management strategies.  Included is a look at studies of personalized biologic therapy and how Abbvie could be using this as a biosimilar defense.  In addition considerable business development activity is current underway in the ASA/Steroid segment as Actavis continues to expand its GI franchise and Shire/Abbvie move towards a merger

• We provide a fully up to date evaluation of biosimilar activity and implications for IBD.  This area continues to move rapidly with Remsima being filed in the US and increasing activity around Humira biosimilars

• A look at the integrin class including early launch information on Entyvio including pricing and how this compares to current therapeutics.  We also provide an analysis of Roche's Phase 3 etrolizumab program and impressive data on Ajinomoto's Phase 2 oral α4β1/α4β7 blocker,  AJM300.  We offer a comparison of how this candidate compares to Entyvio and etrolizumab

• Exciting proof of concept data on novel targets including negative immune regulation by PD-L1-Ig; IL-9 blockade as an approach to UC; elegant work from Ajinomoto leading to the identification of PIKfyve kinase as a target; new data supporting IL-6 (rather than IL-6R) blockade as a therapeutic approach to IBD

• Novo Nordisk's exit from inflammation and possible resultant licensing opportunities

• As part of our ongoing look at supportive care in IBD and especially anemia, we focus on PharmaCosmos which has recently opened two new trials of Monofer in the US

As usual we provide a full update of the IBD landscape (including all molecules we know to be in development for UC and CD).  IBD clinical timelines (interactive charts of Phase 2b and Phase 3 trials, filing dates etc).

Breaking lupus research - September, 2014

Our September issue of UpdatesPlus Lupus is in production and now seems a good time to provide a brief insight into what we will be covering.  

For the September issue we will analyze key events since the August edition including the advancement of Biogen Idec's lupus portfolio as the Phase 1 BIIB059 trials start.  We take the opportunity to evaluate the mechanism of action of this candidate and assess its proof of concept.  

We also highlight new preclinical data currently featured on our DailyUpdates-Inflammation channel supporting B7x as a novel drug target for lupus.  This molecule is a new member of the B7 family; we provide background to B7x and analyze new research linking this to lupus.  Again, relating to early stage R&D we will be looking at EMD Serono's collaboration with Mass General and what this may mean to lupus R&D.  

September is usually a busy month for the drug development sector, with companies presenting investor updates and preparing for key conferences.  We will be providing an analysis of information coming out of the Morgan Stanley Global Healthcare Conference and also preview ACR (coverage of this meeting forms part of our UpdatesPlus service).  This is on top of our regular update of the Lupus pipeline and clinical timelines


This is by no means all that will be in the September issue, simply a taster of what will be included.  To have a look at our August issue, to request notification of when the September issue is available or simply to find out more about our service please contact fiona.watts@leaddiscovery.co.uk

See UpdatesPlus-Lupus August issue

UpdatesPlus-Spondyloarthropathy - Sept 2014 issue now available

The September issue of UpdatesPlus-Spondyloarthropathy is now available. This intelligence service identifies and analyzes key research and development activity across therapy areas including psoriatic arthritis and axial spondyloarthropathies (non-radiographic axial spondyloarthritis and ankylosing spondylitis).  Coverage spans commercial life cycle management, clinical development and pre-clinical proof of concept

In this month we cover:

• Approved biologics: Including a considerable amount of long-term data presented at EULAR earlier this summer, for example data for Humira in nr-Ax-SpA (ABILITY 1 study) and peripheral SpA (ABILITY 2 study);  1-2yr data from Cimzia studies (RAPID-PsA and RAPID-Ax-SpA); and 5yr data for Simponi (GO-REVEAL).  We present Q2 sales figures (including PsA splits).  Of special note Simponi has grown 63% YoY, across all indications driven in part by the launch of Simponi Aria (iv) for RA.  Studies have now been announced for PsA and AS.  
• Otezla:  We report on the early launch performance of Celgene's PDE4 inhibitor in the US.  In particular we discuss reasons for the apparent discrepancy between scripts, impressive market share and sales for the treatment of PsA.  We also discuss the failure of POSTURE to meet its primary endpoint in AS.
• Biosimilars:  We provide a full and up to date overview of biosimilar development in the immunology space.  Most importantly Celltrion has filed Remsima with the FDA
• Pipeline development:  We offer a detailed and up to date status of the spondyloarthropathy landscape along with clinical timelines.  Much focus is placed on the IL-17 mAbs in the present issue, as late stage efficacy reads out for PsO, Amgen/AZ report data for Brodalumab from its Phase 2b PsA study, and Lilly close SPIRIT P1 for enrollment

To receive a full executive summary of this 57 slide report please contact fiona.watts@leaddiscovery.co.uk

Also available are summaries of our recent issues of UpdatesPlus-Psoriasis and UpdatesPlus-Rheumatoid Arthritis

Alert - UpdatesPlus-Heart Failure: RELAX-AHF data reported at ESC describing the impact of worsening HF and the preventative effect of serelaxin

This alert comes from our UpdatesPlus - Heart Failure service, a regular analysis providing depth information on all key recent events in the area.  To receive further information or instruction on how to access the service please contact fiona.watts@leaddiscovery.co.uk

• Novartis has developed human recombinant Relaxin-2 as serelaxin for the potential treatment of AHF

• Teerlink et al previously reported co-primary endpoints from Phase 2/3 RELAX-AHF study

• Only one co-primary endpoint (AUC dyspnea over 5d, a composite of patient’s reported dyspnea on a visual analog scale and the events of worsening heart failure or death) was met with the second (moderate/marked dyspnea over 24hr) not met in the overall study cohort.  The study was however prospectively designed and powered to allow the trial to be considered positive if it met only one of the primary endpoints with a p less than 0.025  (OR both primary endpoints with a p less than 0.05)

• The p value of 0.0075 on the AUC dyspnea over 5d measure was enough to consider the trial positive, but was insufficient for product approval by the FDA which demands a p less than 0.00125 to be considered sufficiently positive for approval on the basis of a single trial. 

• RELAX-AHF specified worsening in-hospital HF as part of the primary endpoint to be recorded in the study and these data were presented for the first time by John Teerlink at ESC

• Worsening heart failure was defined as worsening HF signs and symptoms requiring intensified IV therapies or device support

• RELAX-AHF reported prolonged IV therapies with worsening HF

• The study reported important findings regarding the impact of worsening HF, including increases in various biomarkers (NT-proBNP, hs-cTroponin T and Cystatin-C);  hospital stay (+4.9d in ICU; +8d total hospital stay) and mortality 

• Given the impact of worsening HF and the fact that the AUC dyspnea relief through 5d primary endpoint appeared to be driven by worsening heart failure, the ESC presentation delivered data on the impact of serelaxin on worsening heart failure. 

• RELAX-AHF reported a significant, approximately 50% reduction in death or worsening HF in patients treated with serelaxin vs placebo over 5d

• Of interest, approximately 12% of patients with worsening HF suffered recurrent worsening over 5d and serelaxin significantly reduced both first and recurrent events from a total of 85 events in the placebo- to 41 events in the serelaxin-treated group

Comments:  Despite the serious consequences of worsening HF and the fact that serelaxin appears to reverse this, the FDA review did not accept these data for supporting approval.  This was because RELAX-AHF was a single trial for this new therapeutic agent in an area with multiple failed trials. In addition, while the primary endpoint was significantly improved, the appropriateness of assignment of the worst score to the patients with worsening heart failure was debated. Although the importance of the worsening heart failure events was acknowledged, it was not the primary endpoint, neither were they adjudicated or, according to the reviewer, rigorously measured.  RELAX-AHF also revealed the exciting observation that all-cause and CV mortality were reduced, a finding previously suggested in the Phase 2 Pre-RELAX-AHF study. This possibly mortality benefit prompted the start of Phase 3 RELAX-AHF-2 with CV mortality selected as a primary endpoint.  A second study, the open-label RELAX-AHF-EU study is evaluating worsening HF or mortality at 5d, while RELAX-AHF-Asia is evaluating the effects of serelaxin on a clinical composite within the first 5 days including worsening of heart failure.  If these studies can confirm a reduction in worsening HF or mortality, serelaxin may offer a significant advance.  This would not only be in terms of potential cost savings (as a very rough estimate we suggest the cost of increased ICU and total hospital stay alone could be as high as $30-40,000/patient) but also in terms of mortality.  RELAX-AHF suggests that for every 100 pts treated, 6 may avoid worsening HF, saving a considerable amount in healthcare resources

BMS returns the rights on rheumatoid arthritis candidate, clazakizumab to Alder

The following alert is part of our UpdatesPlus - Rheumatoid Arthritis service.  Read more about clazakizumab and other advances in the field in our August issue  available from fiona.watts@leaddiscovery.co.uk

• BMS has returned the rights to IL-6 mAb, clazakizumab to Alder[link]

• This reportedly follows pipeline reprioritization at BMS rather than efficacy or safety concerns

• 12wk clazakizumab data from a Phase 2b study of MTX-IR rheumatoid arthritis patients was reported at ACR 2013; 24wk data have since been reported at EULAR 2014 and a new TNF-IR study has opened. The second study remains on track to read out in 2015

• Efficacy was high at 24wks in the MTX-IR study (83% ACR20; 48% ACR50), and apparently similar with or without MTX. Serious infections continue to present the greatest AEs especially at higher doses (5%)

• Phase 2b PsA data will be presented at ACR later this year

Comments:  We find BMS' decision a little surprising given the good efficacy reported to date for clazakizumab. During its conference call earlier today, Alder stressed that no new data have emerged that drove BMS' decision. One potential issue that may slow down development and which may have contributed to BMS' decision is the apparent inability to so far select an optimal dose.  Dose ranging studies to date have reported similar efficacy across  doses (25-200mg, q4w).  Of note, Alder has now confirmed that the TNF-IR study is looking at doses under 25mg (the lowest dose investigated in the MTX-IR study).

Another issue is that the IL-6 space is currently competitive, with (Ro)Actemra sales evolving impressively (20-30% YoY growth) and Sarilumab under late stage development.  Clazakizumab is different from both of these molecules in that it targets IL-6 rather than its receptor.  This offers novelty however J&J/GSK have taken a similar approach with sirukumab which is more advanced and currently in Phase 3.  This level of competition may be acceptable to a smaller company such as Alder willing to take a relatively small share of a large IL-6 market, but less so for BMS.  BMS appears to have shaken up its rheumatoid arthritis portfolio recently. BMS-817399, a CCR1 antagonist appears to have been terminated, at least for rheumatoid arthritis following reports of poor efficacy.  BMS-986104 has however entered the pipeline.  The MOA of this candidate is unknown but is orally active

Alert - UpdatesPlus: Novo Nordisk comes out of inflammation

Novo Nordisk is discontinuing all R&D activities within inflammatory disorders in order to focus on metabolic disorders [link]


For further information on this news and all other key breaking research and development across the inflammation arena ask about our UpdatesPlus service (click here for an example)

• The company had active clinical development programs in IBD, Lupus and RA
• In SLE, Novo was conducting Phase 1 studies of NN-8828 (IL-21)
• NN-8828 was also in Phase 2 development for IBD, an indication that Novo has also been developing NN-8555 (NKG2).  Of note, development of NN-8555 was stopped due to futility.  Development was however subsequently restarted following a reanalysis suggesting that efficacy may in fact appear at later timepoints than initially expected
  
• RA was the most advanced therapy areas for Novo, where NN-8226, an IL-20 was being developed.  As discussed in our most recent issue of UpdatesPlus-RA, this candidate was terminated in Phase 2b with ACR20 rates showing no improvement over placebo at 12wks.  Earlier stage candidates were NN-8210, a C5aR antibody.  This Phase 1 candidate was a follow on to NN-8209 which was discontinued last year due to high rates of immunogenicity
  
• Novo has reportedly commented that with the termination of NN-8226, its earliest possible entrance into anti-inflammatory market will be the late 2020s
• The decision will affect ~400 employees, with ~200 being relocated to other parts of the organization

Comments:  Despite today's news, we believe that Novo has an interesting clinical portfolio.  The company has turned out multiple candidates suggesting that behind this portfolio, R&D activities may have many more candidates.  NN-8828 seems to be the most advanced, and we anticipate that launch could be earlier than the late 2020s indicated if developed expeditiously. 

We believe that at least three contributory factory may have underlined Novo's decision to come out of inflammation. 

Firstly, the inflammatory pipeline seems to carry a little more risk than the overall inflammatory disease area.  For example, NN-8555 development was terminated and then re-started, questioning efficacy.  Likewise Novo's C5aR antibodies have been associated with immunogenicity, although this seems to have been resolved. 

Secondly, Novo has limited late stage development expertise in the inflammation arena meaning that speed of development, and establishing market presence may have been doubted internally. 

Thirdly, Novo has suffered manufacturing set backs in recent months - specifically it was forced to delay launch expectations for its long-acting FVIII product (for hemophilia) by about 3 years because it concluded late on in development that capacity was not sufficient.  This has resulted in the company being forced to drastically increase manufacturing capabilities.  This has likely not only forced budget to be diverted away from inflammatory diseases, but also led senior management to question investment required to further increase biologic capabilities had inflammation R&D been continued. 


Overall, we suggest that despite Novo's decision, other companies may want to evaluate the benefit of acquiring Novo's remaining portfolio.  We see opportunities greatest for those companies with pre-existant capabilities and portfolios in the area, and with a need to bolster mid-late term options