
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; |
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 [email protected], or follow @ByMadeleineA or @JacobPlieth on Twitter