The drugs that will shape 2019

We take a look at some of the key drugs that are expected to shape the most important discussions in bio-pharma over the next 12 months, focusing partly on a spate of recent M&A deals and the potential for further industry consolidation…

Zolgensma (formerly AVXS-101) - Spinal Muscular Atrophy (Novartis)

  • A US approval decision for Novartis’ one-time gene therapy treatment in spinal muscular atrophy (SMA) type 1 is expected by May.
     
  • Launch of Zolgensma will sharpen the focus on pricing strategies for gene therapies and mark an important step in the continued transformation of Novartis under the stewardship of CEO Vas Narasimhan, who has shown a willingness to embrace cutting edge technologies over the past year.

See ICER suggests Novartis' gene therapy Zolgensma could be more cost-effective than Biogen, Ionis' Spinraza for spinal muscular atrophy and

ViewPoints: Something old, something new - Can Novartis convince payers that greater biosimilar adoption will loosen the purse strings for innovative therapies?

  • Uptake of Zolgensma will also put pressure on Biogen’s Spinraza franchise, which is currently the only approved therapy for SMA and could prompt further speculation that the biotech will turn to M&A to bolster its portfolio and R&D pipeline.
     
  • We will also get a better idea later in 2019 if Roche’s oral SMA therapy risdiplam is a viable competitor in this space.
     

Upadacitinib/Risankizumab - Rheumatoid Arthritis/psoriasis (AbbVie)

  • AbbVie hopes to secure US approval for its oral JAK inhibitor upadacitinib for the treatment of rheumatoid arthritis by the end of 2019 and approval of its IL-23 inhibitor risankizumab for moderate-to-severe psoriasis by mid-year.
     
  • Analysts are modelling blockbuster sales for both products and key opinion leaders expect each therapy to disrupt the treatment landscape, but will revenue contribution from these new brands be sufficient to offset declining sales from AbbVie’s Humira franchise?

See ViewPoints: The end of an era - AbbVie begins planning for life after Humira

  • Comments from management made at the JP Morgan Healthcare conference last week suggest not; AbbVie says it is willing to consider large deals if they make sense. One option could have been to acquire Bristol-Myers Squibb but that bird appears to have flown.
     

Revlimid - Multiple Myeloma (Celgene/Bristol-Myers Squibb)

  • Bristol-Myers Squibb is, of course, in the process of acquiring Celgene; a deal it says will create an industry-power house in oncology. Those taking a more sceptical slant claim that Celgene is cheap due to management missteps over the past two years and Bristol-Myers Squibb is in need of growth impetus with the outlook for its immunotherapy portfolio blunted my Merck & Co.’s dominance of this market.

See ViewPoints: The hunted goes hunting – for liberty and a late-stage pipeline

  • Regardless, ensuring generic versions of Revlimid - Celgene’s cash cow - are delayed for as long as possible will be imperative if Bristol-Myers Squibb is to maximise its return from the deal, despite the near term conveyor belt of potential new drug launches it has inherited from Celgene (see below).
     
  • Analysts at Bernstein recently suggested Revlimid generic launches before 2020 look unlikely and pegged 2023 as the most likely entry point. 
     

bb2121 - Multiple myeloma (Celgene/Bristol-Myers Squibb)

  • CAR-T had its watershed moment two years ago with the approvals of Kymriah (Novartis) and Yescarta (Gilead Sciences) but this new therapeutic modality remains a key focal point for the industry.
     
  • This is due in equal measure to the potentially curative nature of CAR-T and its role as a future disruptor (like gene therapy) of traditional drug pricing norms. Furthermore, Novartis has conceded that despite the approval of Kymriah, CAR-T is a steep learning curve; the Swiss company is working hard to overcome manufacturing challenges, it said earlier this month.
     
  • 2019 should see the next notable CAR-T product progress from clinic to the regulatory arena, with bluebird bio and Celgene’s BCMA-targeted product bb2121 due to be submitted to the FDA as a treatment for refractory multiple myeloma.
     
  • bb2121 has impressive data on its side but may face off against GlaxoSmithKline’s GSK2857916, an antibody-drug conjugate (ADC) directed against BCMA which could also be filed with the FDA later this year.
     
  • Data released for GSK2857916 so far is early but impressive and the drug will likely be cheaper, more accessible and more ‘scalable’ than CAR-T therapy. A potentially fascinating showdown waits between a ‘wants to be’ rejuvenated GlaxoSmithKline and Bristol-Myers Squibb’s management team, which will be determined to execute on the Celgene acquisition.

See ViewPoints: Bristol-Myers Squibb, GlaxoSmithKline primed for potential multiple myeloma show down
 

Zejula - Ovarian Cancer (Tesaro/GlaxoSmithKline)

  • And on the subject of GlaxoSmithKline’s rejuvenated aspirations in oncology, its acquisition of Tesaro for $5.1 billion in December puts the latter’s PARP inhibitor Zejula firmly in the spotlight this year.
     
  • Drugs in this class have shown considerable promise in selected patient cohorts; data presented for AstraZeneca and Merck & Co.’s Lynparza at ESMO in October - showing practice changing results as a first-line maintenance therapy in BRCA mutated ovarian cancer - were one of the highlights of 2018’s clinical data releases.
     
  • GlaxoSmithKline is banking on Zejula having broader applicability with a study already underway designed to show whether Tesaro’s PARP can demonstrate a similar effect in first-line ovarian cancer but not limited to the 15 percent or so of patients who are BRCA mutated. Positive data would expand the commercial opportunity for Zejula considerably and provide a timely boost to GlaxoSmithKline’s oncology credentials.

See ViewPoints: GlaxoSmithKline pulls the M&A lever to move back into oncology and looks to get one over on AstraZeneca
 

Vascepa - dyslipidaemia (Amarin)

  • Following positive results last year showing a 25-percent risk reduction in major adverse cardiovascular events, the FDA is currently reviewing a supplementary new drug application for Vascepa, Amarin’s purified fish oil product that could lead to a significant increase in sales; despite some question marks over the performance of the placebo arm in the REDUCE-IT study.

See KOL Views Results: Vascepa outpaces questions about placebo to score big win in REDUCE-IT, says leading cardiologist

Zulresso/SAGE-217 - Depression (Sage Therapeutics)

  • Sage has already delivered a key update in the first few weeks of 2019 by announcing positive data earlier this month for its oral drug SAGE-217 in postpartum depression (PPD)
     
  • Zulresso - a mechanistically similar drug which requires infusion - is already under FDA review for PPD with an approval decision expected by the end of Q1. The key event to watch, however, is the potential read out of Phase III data for SAGE-217 in major depressive disorder later this year.
     
  • Positive data would go a long way to confirming the argument that Sage is perfecting a way to tackle the development of novel depression drugs against an overwhelming tide of late-stage setbacks from the field at large.

See ViewPoints: Could Sage Therapeutics be biopharma's next acquisition target?

BAN2401/aducanumab - Alzheimer’s disease (Biogen)

  • Any updates for BAN2401 and aducanumab over the next 12 months are expected to be only incremental but will nevertheless be keenly watched, thanks to the continued lack of definitive breakthroughs in tackling Alzheimer’s disease (which extends to understanding the condition itself let alone approaches to modify it) and the teasing out of ostensibly positive data for BAN2401, which was presented last year.
     

See ViewPoints: Biogen, Eisai flip the script with BAN2401 raising new queries
 

Opdivo - Non-small-cell lung cancer (Bristol-Myers Squibb)

  • Bristol-Myers Squibb's Opdivo may technically still be the market's leading checkpoint inhibitor, but there's no question that Merck & Co.'s Keytruda has hugely diminished its prospects in NSCLC. The company's next best shot to claw back market share in the first line setting is through a potential approval for an Opdivo/Yervoy combo, inspired by the TMB biomarker analysis of the Checkmate-227 study. The FDA's decision deadline for the application is February 20, 2019.
  • Outside of NSCLC, one of the relatively few spaces left open for Opdivo to make an impact is an early stage and adjuvant lung cancer setting. AstraZeneca's Imfinzi has already drawn first blood, however, via its PACIFIC study supporting an approval in Stage III patients with unresectable disease that has not progressed after chemo-radiation therapy (CRT).

See ViewPoints: Where next for pharma's hottest drug class? - Expect focus to sharpen on use of anti-PD-(L)1 therapies in adjuvant lung cancer

  • Bristol-Myers Squibb is also likely to spend some time shopping in its closet to see if any of the candidates coming on board from Celgene offer a good fit as part of a combination regimen to up the efficacy for Opdivo.
     

VX-659/ivacaftor/tezacaftor  - Cystic fibrosis (Vertex)

  • VX-659 is a member of one of the two triplet combinations that Vertex is evaluating in Phase III studies for cystic fibrosis (CF), as the company runs through the paces to optimise combinations of next-generation potentiators and correctors to pair with its existing products Kalydeco (ivacaftor) and Symdeco (ivacaftor/tezacaftor). The company is expecting its first Phase III readout this quarter for VX-445/ivacaftor/tezacaftor, with an NDA planned for mid-year- though it hasn't yet decided between the VX-445 and -659 programmes.

See ViewPoints: Vertex’s VX-659 data set a high bar – for itself

  • Vertex has already set and reset the bar for triplet combos in CF, setting it far ahead of the competition in terms of both efficacy and time to market. However, after previously seeming to waffle on its decision to maintain its CF partnership with Galapagos, AbbVie instead took full control of the programme, giving Vertex a much better-heeled competitor to contend with in 2019.
  • A key sticking point for Vertex's eventual marketed products could be price. The company is already at a reimbursement crossroads with multiple EU countries that have been unable to agree on a price for the company's approved doublets, suggesting that adding a third drug to the mix will only exacerbate the situation.
     

Tanezumab - osteoarthritis pain (Pfizer and Eli Lilly)

  • Backlash against opioids has opened up new opportunities for old products in pain management, led by Pfizer and Eli Lilly with nerve growth factor (NGF) inhibitor tanezumab. The drug class has been associated with rapidly progressing osteoarthritis and bone necrosis, but a Phase III readout from tanezumab late last year helped to allay safety concerns- although it didn't necessarily silence them.

See ViewPoints: Tanezumab data underscore delicate balancing act for NGF inhibitors

  • Additional readouts are expected for the tanezumab programme throughout 2019, including longer-term studies that should provide a more satisfactory answer to safety questions. Expect those results to also have knock-on effects for other late-stage programmes at Regeneron and Amgen.
     

Ocaliva (obeticholic acid) – non-alcoholic steatohepatitis (Intercept)

  • Intercept will be carrying much of the NASH universe on its shoulders in 2019, as it presents the first Phase III data for an FXR agonist. The company moved the agent into a pivotal programme based on the results of the FLINT study, and a swath of companies have since pursued the target- and many others- to take on the hugely lucrative indication. However, Intercept's positioning gives it potential first-to-market status, with the extra advantage of physician familiarity via its existing approval in primary biliary cholangitis- assuming that is considered a positive, given the product's safety track record in the indication.
  • Despite Intercept's strong positioning, other companies have already moved on to new and improved versions of the same target, as well to combination approaches- all suggesting that should Intercept win a first approval, the field could nonetheless leave Ocaliva behind.

See ViewPoints: What's new in NASH- the state of the art in FXR agonists

  • While Intercept has the official first look, Genfit and Gilead will present their own Phase III readouts later in 2019 for elafibranor and selonsertib, respectively, queueing up a string of important NASH disclosures to shape the field in 2019.
     

Vitrakvi –NTRK gene fusion-positive tumours (Eli Lilly)

  • Eli Lilly just spent $8 billion to acquire Loxo Oncology and its genetically-defined oncology treatment, and now faces the challenge of marketing a product that is useful for about 1 percent of all cancer patients. While prescribers polled by FirstWord are impressed with the drug, identifying patients will still be a key issue, and the extent to which Eli Lilly and partner Bayer succeed in doing so is likely to trickle down to the RET-targeting programmes in the Loxo pipeline, as well as the competition at Blueprint Medicines.

See ViewPoints: Eli Lilly embraces precision medicine with Loxo acquisition

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