The drugs that will shape 2018

FirstWord takes a closer look at the leading products likely to dominate industry news flow over the next 12 months...

Bictegravir (HIV) – Gilead Sciences

Gilead Sciences is expected to wrestle back initiative in the HIV market this year with approval and launch of its integrase inhibitor bictegravir. Formulated into a fixed-dose triple combination with emtricitabine and tenofovir alafenamide (TAF), Gilead's latest offering is forecast to slow momentum for ViiV Healthcare's Tivicay and Triumeq brands (ViiV majority partner GlaxoSmithKline has conceded as much). Despite strong growth for Tivicay in recent years, familiarity with Gilead's backbone drugs will be critical in driving adoption of its new combination suggest physicians, while ViiV's focus on dual combinations – offering reduced risk of toxicity, but arguably higher risk of disease resistance – looks likely to provide limited insulation.

Further analysis: Physician Views Poll Results: ViiV's Juluca faces an uphill task and Physician Views Poll Results: 'Show a little backbone' – Gilead's existing HIV drugs critical to adoption of newbie bictegravir.

Oral semaglutide (diabetes) – Novo Nordisk

Having secured US approval of Ozempic late last year, Novo Nordisk looks set to consolidate its leadership of the GLP-1 agonist class in the type 2 diabetes market. This year, it could go a step further if Phase III data for its oral form of semaglutide is positive. Assuming efficacy is on par with injectable agents, this product could revolutionise the treatment of diabetes, argue key opinion leaders, and accelerate use of the GLP-1 class into earlier lines of therapy.

Further analysis: KOL Views Results: Leading clinician sees semaglutide as incremental improvement on Trulicity, with paradigm shift still to come.

PD-1/PD-L1 inhibitors (non-small-cell lung cancer) – various

2018 could prove to be a critical year in determining how the PD-1 and PD-L1 inhibitors are used as first-line treatments for non-small-cell lung cancer. Thanks to pending Phase III data readouts from AstraZeneca and Bristol-Myers Squibb, we should get a definitive idea if PD-(L)1/CTLA-4 inhibitor combinations are superior to chemotherapy in this setting. While confidence in this approach has waned over the past 12 months, the argument in favour of combining a PD-(L)1 with chemotherapy has gained credibility. By the end of 2018 we should also have a better idea as to how this approach stacks up versus current standard of care.

Further analysis: ViewPoints: Merck & Co.'s early-bird data stops Roche from taking flight out of ESMO-IO, ViewPoints: EMA sheds further light on key Keytruda data in shadow of Roche's big reveal and Physician Views Poll Results – Oncologists predict 'considered' use of Keytruda/chemo combo in first-line NSCLC.

Epacadostat (melanoma) – Incyte  

We should also get a much clearer view as to whether PD-(L)1 and IDO inhibitor combinations work. Phase II data from non-randomised studies has impressed, but the real benchmark will be set by results from ECHO-301, Merck & Co. and Incyte's Phase III combination study of Keytruda and epacadostat in first-line melanoma, which are expected in the first half of 2018. Simply put, earlier-stage data indicates that this mechanistic pairing mimics the efficacy seen with Bristol-Myers Squibb's PD-1/CTLA-4 combo of Opdivo/Yervoy, but with less toxicity. If results are positive, expectations will rise further for a raft of Phase III trials already initiated in other tumour types, including first-line NSCLC.

Further analysis: ViewPoints: Why Incyte remains the immuno-oncology upstart to watch and ViewPoints: ESMO 2017 - more of the same at Incyte makes for a rousing success.

CAR-T/gene therapy – various

Following initial regulatory approvals last year, focus will remain sharpened on the marketed CAR-T products in 2018 – Novartis' Kymriah and Gilead's Yescarta – to see if revolutionary science translates into commercial success. Any additional data for Juno Therapeutics' JCAR017 will also be scrutinised to see whether this CAR-T offers superior efficacy and safety; earlier data had hinted at this possibility, but results at the ASH annual meeting in November suggest the playing field is level.

See also Spark Therapeutics' Luxturna, the first gene therapy approved in the US, which could be priced at $1 million for a one-time treatment.

Further analysis: KOL Views Results: Leading oncologist says CAR-T therapies look more similar than different in DLBCL.

Ozanimod (multiple sclerosis) – Celgene

Ocrevus has provided real disruption in the multiple sclerosis market, but the jury is out on whether Celgene's Ozanimod – due to be approved later this year – can follow suit. The proposition put forward in favour of the drug is efficacy on par with the oral agent Gilenya minus the monitoring requirements that sometimes prompt neurologists to reach for an alternative therapy. Phase III clinical data back the argument up, but key opinion leaders remain somewhat unconvinced; particularly with generic versions of Gilenya not far away.

Further analysis: KOL Views Results: Ozanimod differentiates itself from Gilenya but Celgene has a tricky choice on pricing, says leading neurologist and Physician Views Poll Results: Ozanimod is compelling, but cardiac benefits may hold limited sway against price.

Imfinzi (stage III NSCLC) – AstraZeneca

AstraZeneca delivered an under-the-radar win last year when its Phase III PACIFIC trial showed a positive result, demonstrating that use of the PD-L1 inhibitor Imfinzi significantly improved progression-free survival in stage III NSCLC patients who had previously responded to current standard-of-care therapy. AstraZeneca is expected to update results with overall survival data later this year and should also secure US and EU approval. Focus then will shift on to rate of adoption, with Imfinzi likely to benefit from a two to three year head start over rival PD-(L)1 inhibitors in this treatment setting.

Further analysis: ViewPoints: Onus may now be on the FDA to speed through approval of AstraZeneca's PACIFIC data and Spotlight On Interview: AstraZeneca strikes back.

Olumiant (rheumatoid arthritis) - Eli Lilly

Having quickly appeased the FDA about potential safety concerns, Eli Lilly expects to resubmit its JAK inhibitor with the agency in early 2018, setting up potential approval before year end. Experts are impressed with Olumiant's efficacy and Eli Lilly is in need of momentum from new product launches.

Furthermore, its filing with the FDA will be the first of multiple catalysts in the immunology market during 2018; additional Phase III data will continue to read out for AbbVie's upadacitinib in rheumatoid arthritis (RA), culminating in potential regulatory submissions towards year end; Phase III data for Gilead and Galapagos' competing JAK inhibitor filgotinib (also in RA) will read out in the first half of 2018, as will full Phase III data for AbbVie and Boehringer Ingelheim's antibody agent risankizumab in psoriasis. These will occur against the backdrop of likely greater incursion by biosimilar anti-TNF products.  

Further analysis: ViewPoints: Bar set high for AbbVie, Boehringer Ingelheim's push into psoriasis and Physician Views Poll Results: Xeljanz better known, but Olumiant looks to have the cutting edge.

Aimovig (migraine) – Amgen/Novartis

Amgen and Novartis' Aimovig should be approved by the FDA on or before May 17 and will become the first CGRP inhibitor to reach the market for the treatment of migraine. Competition in this market will be intense with three similar drugs also nearing the market (Teva and Eli Lilly's anti-CGRPs should also be approved in the US in 2018). These antibodies have shown similar efficacy at preventing and reducing the frequency of migraines. 2018 will also see pivotal data for two oral CGRPs announced.

Further analysis: Physician Views Poll Results – Does neurologist/PCP feedback give new migraine players a headache? and KOL Views Results: Leading neurologist opines on what is likely to differentiate anti-CGRP mAbs in marketplace.

Lanadelumab (hereditary angioedema) – Shire

Shire announced positive Phase III data for its hereditary angioedema (HAE) treatment lanadelumab back in May and is expected to file a regulatory application with the FDA imminently, which should set up approval before the end of 2018. A successor to Shire's preventative therapy Cinryze, lanadelumab will face competition in the HAE market from CSL's Haegarda, which was approved last year. Shire is banking on improved convenience as a key selling point, but both companies should benefit from expansion of the prophylactic treatment market.

Further analysis: Spotlight On Interview: CSL offers clues about how it will position Haegarda against HAE foes both new and old and KOL Views: Big changes are in store in the HAE prophylactics space, according to leading immunologist.

Rova-T (small cell lung cancer) – AbbVie

AbbVie saw its share price appreciate significantly over the course of 2017, thanks largely to investors growing increasingly confident that flagship product Humira will remain patent protected in the US into the early 2020s. Against this backdrop, however, the onus is on AbbVie management to deliver wins from the late-stage pipeline. 2018 will see results from the pivotal Phase II TRINITY study – assessing Rova-T in small cell lung cancer – read out, which could pave the way for approval later in the year. With Rova-T acquired as part of the $5.8-billion purchase of Stemcentrx in 2016, expectations remain high.

Further analysis: Spotlight On: AbbVie’s BD acumen – fairly or not – on the line with looming TRINITY readout.

Various cystic fibrosis therapies – Vertex/Galapagos

Vertex Pharmaceuticals – which remains hotly tipped as a Big Pharma takeout candidate by analysts – will provide additional Phase II data readouts for its triple combination cystic fibrosis candidates in 2018 and should also secure regulatory approval of its VX-661/Orkambi pairing in patients with homozygous or F508del/residual function mutations. Concurrently, however, future competitive threats could become more visible, with Galapagos leading the way (despite being approximately two years behind Vertex).

Further analysis: ViewPoints: Galapagos comes up short of a triple play, but still chugs along and ViewPoints: Vertex’s triplet data raise bar and turn screws on CF competition.

Larotrectinib (TRK fusion cancers) – Loxo Oncology/Bayer

Loxo confirmed last month it has filed a rolling new drug application with the FDA for larotrectinib as a treatment of unresectable or metastatic solid tumours with NTRK-fusion proteins, irrespective of histology. This announcement comes shortly after Loxo secured a partnership with Bayer for larotrectinib and coincided with Roche's acquisition of Ignyta; Ignyta's entrectinib is being developed for a similar genetically defined cancer indication. Last year, Merck & Co.'s Keytruda became the first cancer therapy to be approved by the FDA for genetically defined tumours irrespective of histology (in unresectable or metastatic solid tumours that are driven by either microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) genetic alterations.

Further analysis: KOL Views: Leading oncologist outlines road forward and potential pitfalls ahead in new era of genetically defined cancer drugs and ViewPoints: Loxo shareholders underwhelmed by Bayer deal.

ALXN1210 (paroxysmal nocturnal haemoglobinuria) – Alexion

Alexion Pharmaceuticals has fallen from its perch as one of biotech's most admired companies in recent years, but its outlook could be revitalised if ALXN1210 – a potential successor to its flagship drug Soliris – delivers positive Phase III data in both naïve and switch paroxysmal nocturnal haemoglobinuria (PNH) patients later in 2018. Expectations have grown due to emerging competitive threats in the PNH space; ALXN1210 may offer greater convenience for patients, but the question is whether it will provide superior efficacy.

Further analysis: ViewPoints: Alexion plays offense and defence with Halozyme deal and ViewPoints: Investors suspect Alexion’s Soliris franchise just dodged another bullet.

AVXS-101 (spinal muscular atrophy) – AveXis

In late 2016, Biogen and Ionis Pharmaceuticals' secured approval for Spinraza as a first ever therapy for spinal muscular atrophy (SMA); now AveXis wants a piece of the action and AVXS-101 could be filed for the treatment of type 1 SMA patients later this year on the strength of Phase I data. Later this year, Biogen will also start trials of an experimental gene therapy in SMA.

Further analysis: ViewPoints: FDA’s leeway for AveXis in Type 2 SMA may presage path in Type 1 and ViewPoints: Biogen looking to take the long view on SMA.

Epidiolex (Lennox-Gastaut/Dravet syndrome) – GW Pharmaceuticals

Clinical data in support of GW Pharmaceuticals' Epidiolex have accumulated steadily in recent years and the drug recently entered the regulatory arena, setting up potential US approvals for the treatment of Lennox-Gastaut syndrome and Dravet syndrome later in 2018.

Further analysis: ViewPoints: Zogenix fattens up on ZX008’s big win in Dravet syndrome – is it really a loss for GW Pharma? and ViewPoints: Extra leverage may have just fallen in GW Pharmaceuticals’ lap.

Patisiran (hereditary ATTR amyloidosis) – Alnylam Pharmaceuticals/Sanofi

In September, Alnylam Pharmaceuticals and partner Sanofi delivered the first positive data for an RNAi therapeutic in a Phase III study – for patisiran as a treatment for hereditary ATTR amyloidosis with poly neuropathy – and regulatory applications have quickly followed; setting up potential approvals in 2018 and 2019.

Further analysis: ViewPoints: Showtime at the APOLLO for Alnylam and ViewPoints: Alnylam handed officially unofficial boost in ATTR amyloidosis battle.

Apalutamide (prostate cancer) – Johnson & Johnson

Johnson & Johnson hasn't yet presented late-stage clinical data for apalutamide, but has submitted it to the FDA for the treatment of non-metastatic castration-resistant prostate cancer (CRPC); furthermore, the agency recently granted it priority review status. Apalutamide (formerly known as ARN-509) has a lot riding on it. Johnson & Johnson paid $650 million upfront plus up to $350 million more in milestones to buy Aragon Pharmaceuticals in 2013 based on Phase II data in CRPC.

Further analysis: ViewPoints: Johnson & Johnson puts cart before horse with apalutamide – time must be of the essence.


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