Glaxo gets out the axe

Glaxosmithkline’s announcement of a pipeline cull comes just a day after Lilly said it would do the same – and both appear to be cases of two new leaders trying to make their mark. The UK group is ditching over 30 projects including 13 clinical programmes, with the most high-profile casualty being the rheumatoid arthritis candidate sirukumab (see tables below).

The move confirms previous hints by Glaxo’s new chief executive, Emma Walmsley, that the company would concentrate on fewer, larger, pipeline opportunities. But a renewed focus on oncology raises questions over the group’s past strategy – and whether acquisitions might now be on the cards.

As well as oncology, Glaxo plans to plough most of its resources into respiratory, HIV/infectious diseases and immuno-inflammation. This leaves no room for its rare diseases unit, for which the company said it was considering options.

Among the projects Glaxo is prioritising are oncology assets, including two targeting the novel immune system checkpoints Ox40 and Icos. While Ox40 has been touted as one of the targets that will usher in a new wave of post-PD-(L)1 agents, strongly positive clinical data from the likes of Roche (RG7888) and Astrazeneca (MEDI6469) have been painfully slow to emerge.

Glaxo's key pipeline assets
Project Indication Mechanism Status
Respiratory
Closed triple  COPD ICS/LABA/LAMA Filed
Danirixin COPD CXCR2 antagonist Phase II
Nemiralisib COPD PI3Kδ inhibitor Phase II
HIV
Dolutegravir + rilpivirine HIV infection HIV integrase inhibitor & NNRTI Filed
Dolutegravir + lamivudine HIV infection HIV integrase inhibitor & NNRTI Phase III
Cabotegravir HIV infection and pre-exposure prophylaxis  Long-acting HIV integrase inhibitor Phase III
Oncology
GSK3174998 Solid tumours and haematological malignancies OX40 agonist mAb Phase I/II
GSK3359609 Cancer ICOS agonist mAb Phase I/II
GSK525762 Solid tumours and haematological malignancies BET inhibitor Phase I/II
GSK2857916 Multiple myeloma BCMA-ADC Phase I/II
GSK3377794* Sarcoma, multiple myeloma, NSCLC, melanoma, ovarian cancer NY-ESO-1 TCR Phase II
Immuno-inflammation
Tapinarof Atopic dermatitis and psoriasis Topical NSAI Phase II
GSK2982772 Psoriasis, rheumatoid arthritis and ulcerative colitis RIP-1 kinase inhibitor Phase II
GSK3196165 Rheumatoid arthritis and osteoarthritis  Anti-GM-CSF Phase II
Other
Daprodustat Anaemia associated with chronic renal disease Oral PHI Phase III
GSK2398852 + GSK2315698  Amyloidosis Anti-SAP MAb + SAP depleter Phase II
*Option deal with Adaptimmune. Source: company presentation.

Also being retained are an antibody-drug conjugate against BCMA – an important multiple myeloma target for CAR-T therapies from Bluebird, Kite, Juno and Novartis – and an engineered T-cell therapy against NY-ESO1 that is Adaptimmune’s lead cell therapy asset. Clearly, after the divestment of Glaxo’s marketed oncology drugs to Novartis, the UK group has worked to build an early, novel pipeline here.

Going, going, gone

However, several cancer assets have been put on the back burner for termination, licensing out or divestment. These include the Epizyme-partnered EZH2 inhibitor GSK2816126 and the LSD1 inhibitor GSK2879552, though the latter only in small-cell lung cancer.

Both terminations cast more doubt on the promise of epigenetics as pharmacological strategy. Just last week Roche terminated a deal with Oryzon Genetics’ lead asset, ORY-1001, which also targets LSD1, citing an internal review (Roche’s Oryzon farewell spells more bad news for epigenetics, July 20, 2017).

Facing the chop – Glaxo's discontinued projects
Project Indication Mechanism Status
Infectious diseases
GSK2878175 Hepatitis C  NS5B polymerase inhibitor Phase II
Danirixin IV Influenza CXCR2 antagonist Phase I
Oncology
Tarextumab* SCLC Notch 2/3 MAb Phase II
GSK2816126** Solid tumours and haematological malignancies EZH2 inhibitor Phase I
GSK2879552 SCLC LSD1 inhibitor Phase I
Immunoinflammation
Sirukumab Rheumatoid arthritis IL-6 MAb Filed
GSK3050002 Psoriatic arthritis  CCL20 MAb Phase I
Metabolic
Retosiban Spontaneous pre-term labour Oxytocin antagonist Phase III
GSK2330672 Cholestatic pruritis iBAT inhibitor Phase II
GSK2798745 Heart failure TRPV4 antagonist Phase II
Daprodustat Wound healing Topical PHI Phase I
GSK3008356 Non-alcoholic steatohepatitis DGAT 1 inhibitor Phase I
Dermatology
GSK2981278 Psoriasis Topical ROR gamma inverse agonist Phase II
*Option deal with Oncomed; **licensed from Epizyme; studies in AML and MDS to continue. Source: company presentation.

Of the programmes that Glaxo plans to partner or divest, perhaps the most surprising is sirukumab, now brand-named Plivensia, a joint project with Johnson & Johnson that is due to face an FDA panel next week.

It is unclear why Glaxo is ditching this project at such a late stage. Perhaps it is put off by an increasingly crowded rheumatoid arthritis market, or maybe it would prefer to focus on wholly owned assets. Sirukumab is forecast to bring in $1.2bn by 2022, according to EvaluatePharma sellside consensus, but Glaxo is only set to see $598m of this.

Either way, it looks like bad news for Ablynx, which has been trying to find a new partner for its own IL-6 MAb vobarilizumab since Abbvie walked away last year (Abbvie exit forces Ablynx into plan B, October 20, 2016).

Ms Walmsley admitted that Glaxo had spread itself too thinly, and spent too much on developing projects that had ultimately failed to deliver. The company launched 25 new products in 2006-15, above the average among its pharma peers – but estimated peak sales of $600m per drug are among the lowest in the industry.

Today’s move was decisive, but it has not been popular: Glaxo’s shares fell nearly 3% this morning. It seems that investors fear that Glaxo is in for more pain before it will realise any gains from its new strategy.

To contact the writer of this story email Madeleine Armstrong or Jacob Plieth at news@epvantage.com, or follow @ByMadeleineA or @JacobPlieth on Twitter

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