R&D roundup – Sage impresses at JP Morgan

One of the biggest headline-grabbers at the 2019 JP Morgan Healthcare conference this week was Sage Therapeutics unveiling promising data from an up-rated phase III trial of its postpartum depression (PPD) drug SAGE-217, causing the company’s share price to surge by over 40%.

After two weeks of outpatient treatment, SAGE-217-treated women had an almost 18-point improvement on the Hamilton Depression Rating Scale (HAM-D), while those on placebo showed a 13.6% increase. Moreover, at the end of the treatment 45% of women on Sage’s drug were in remission, compared to 23% of the placebo arm.

It’s that rapidity of onset that is generating the excitement about SAGE-217, as the current antidepressant armamentarium can take weeks or even months to start working. Importantly, there were no reports of fainting (syncope) in the trial, alleviating earlier concerns that this could be an issue with the drug.

Sage is already waiting for the FDA to complete its review of GABAA modulator Zulresso (brexanolone), which is given as a 60-hour intravenous infusion and is intended to treat severe, acute cases of depression in hospital. If approved by the 19 March action date – which seems likely after an advisory committee voted overwhelmingly in favour of the drug last November – it will be the first drug specifically indicated for PPD in the US.

SAGE-217 has the same mechanism of action but can be given orally, potentially making it suitable for a much broader patient population. It has already picked up a breakthrough designation from the FDA, and last June the FDA confirmed Sage could file for PPD on the strength of a single phase II trial – the first time that this expedited route had been made available for an antidepressant.

In other conference news, Celltrion said that its main focus for 2019 would be the development of a subcutaneous version of its Remicade biosimilar CT-P13. Subcutaneous formulations provide patients with the opportunity to self-inject which can lead to enhanced convenience and time saving by allowing them to receive treatment at home.

The subcutaneous version of CT-P13 has been shown to be comparable to the intravenous (IV) version of CT-P13 in terms of pharmacokinetics, immunogenicity, efficacy and safety in patients with active rheumatoid arthritis and active Crohn's disease patients for 30 weeks.

Meanwhile, Axsome Therapeutics announced that AXS-05 (45 mg dextromethorphan/105 mg bupropion), and its investigational NMDA receptor antagonist, met its primary endpoint and significantly improved symptoms in a phase II trial in major depressive disorder (MDD). The drug demonstrated a 17.2 point reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score compared to a 12.1 point reduction for comparator drug bupropion.

With news of Lilly’s $8 billion acquisition purchase of Loxo Oncology fresh in everyone's minds, companies presenting at JP Morgan were divided on whether similar deals would be in consideration for them. GSK’s CEO Emma Walmsley said that her company will actively look to buy early-stage assets and partner; AbbVie and Gilead made similar comments – while Biogen played down the need for M&A.

Biogen boost CNS pipeline

Biogen has signed a brace of collaborations to expand its central nervous system (CNS) pipeline, adding new candidates for Alzheimer’s, multiple sclerosis and other neurological diseases.

The first of the new deals is a $415 million collaboration with protein degradation specialist C4 Therapeutics, focusing on Alzheimer’s, Parkinson’s and other neurological diseases.

C4T’s platform focuses on the use of small-molecule drugs – called degronimids – that can target, degrade and clear proteins through the ubiquitin/proteasome pathway, and could potentially target proteins that so far have proved to be “undruggable.”

Biogen is also paying Skyhawk Therapeutics $74 million upfront to license therapeutic candidates for MS, spinal muscular atrophy (SMA) and other diseases developed using its RNA platform, plus undisclosed milestones.

Skyhawk’s approach is to develop small-molecule drugs that can correct RNA mis-splicing leading to loss of RNA expression by exon-skipping. It is another way to go after hard-to-target disease mechanisms and according to Skyhawk could have particular utility in diseases caused by the loss of function of key proteins that are hard to tackle with antisense drugs or gene therapies.

The two deals continue Biogen’s tight focus on neurology – first pursued in 2016 when it spun off its haemophilia business into Bioverativ (since acquired by Shire) – but contribute to an ongoing effort to reduce the company’s reliance on a portfolio of fast-maturing MS therapies headed by Tecfidera (dimethyl fumarate) which has started to see sales flatten.

Biogen currently has five potential Alzheimer’s treatments and one Parkinson’s treatment in development, and analysts have become concerned that its focus on tough-to-treat diseases make its pipeline very high risk despite other projects in stroke, MS, lupus and other diseases.

New data shows AbbVie and J&J’s arthritis dominance

AbbVie and Johnson & Johnson (J&J) are responsible for 47 of the 121 industry sponsored clinical trials in the psoriatic arthritis space, according to GlobalData.

The company’s latest report: ‘Psoriatic Arthritis: Competitive Landscape to 2026’ found that industry sponsors are responsible for over 70% of psoriatic arthritis clinical trials, with the top seven industry sponsors accounting for 64% of all industry sponsored trials.

J&J and AbbVie have been the dominant players in the psoriatic arthritis market since the introduction of Remicade (2004) and Humira (2005) as the second and third TNF inhibitors approved by the FDA, respectively.

“The psoriatic arthritis market has become increasingly competitive, with both subcutaneous and intravenous therapies being available as well as two oral small molecules and biosimilars,” said Alexandra Annis, MS, managing pharma analyst at GlobalData. “However, J&J and AbbVie are slated to remain headliners in the psoriatic arthritis marketplace, looking to capitalise on the excitement surrounding interleukin inhibitors and janus kinase inhibitors.”