Friday Five – Your weekly pharma review

CAR-T is go!

History was made on Wednesday when the FDA approved the world's first CAR-T therapy: Novartis' Kymriah (also known as tisagenlecleucel or CTL019) for the treatment of relapsed acute lymphoblastic leukaemia (ALL) in paediatric and young adult patients.

Approval of Kymriah represents an important first step to revolutionising blood cancer therapy (and potentially in the longer term, treatment of solid tumours), say key opinion leaders (KOLs), although initial post-approval focus has largely been on Novartis' pricing strategy, which could have profound implications for other CAR-T players, such as Gilead Sciences (see below).

As a one-off treatment, Kymriah will cost $475,000 per patient in the US; a price that is simultaneously below what many had anticipated, but which has nevertheless attracted scrutiny, particularly in the context of Kymriah working as a 'bridge to transplant' rather than curative therapy. Most significantly, however, patients will only be billed for treatment with Kymriah if they have been shown to respond to therapy after a month; a move that both cements Novartis' status as a progressive company regarding outcomes-based pricing, and could set a precedent for other CAR-T therapies irrespective of indication – ViewPoints: Novartis sets the stage for CAR-T commercialisation, but your price may vary.


…and Gilead is in the running

So what is Gilead thinking about Novartis' pricing strategy for Kymriah? At the beginning of the week, the biotech agreed to acquire CAR-T specialist Kite Pharma for $11.9 billion

Kite's axicabtagene ciloleucel (or 'axi-cel') is awaiting FDA approval for the treatment of non-Hodgkin's lymphoma and Gilead can at least now be more confident of regulatory clearance ahead of axi-cel's scheduled PDUFA date in late November; particularly as approval of Kymriah came more than a month earlier than expected.

Based on initially approved indications, the population eligible for treatment with axi-cel will be considerably larger than that for Kymriah (at approximately 7000 versus 650 patients per annum in the US) and this is expected to play an important role in determining the price that Gilead sets. So too will lower response rates for CAR-T treatment in NHL versus ALL, which will presumably determine whether, or how, outcomes-based pricing can be used in different indications.

See ViewPoints: With no pricing war on the horizon in CAR-T, the sky's the limit for Gilead and Novartis

All signs therefore point to a lower launch price for axi-cel (versus that of Kymriah in ALL; Novartis expects indication-based pricing in the future), but Gilead is, nevertheless, well placed to weather any pricing controversy given its recent experience in the hepatitis C market. In this regard, acquisition of Kite shares some similarities to Gilead's purchase of Pharmasset back in 2011; both in terms of financial outlay and the company's need to acquire growth in order to offset a pending decline in revenues from its existing portfolio.

However, there are also marked differences. Gilead's transition from a company focused on HIV to one expanding into the hepatitis C market was logistically much more straightforward than its current push into oncology, where it has already suffered a number of disappointments and the integration of Kite will need to be carefully managed (given both Kite's status as a pioneering player in a new therapeutic modality and Gilead's prior focus only on small-molecule drugs).

Furthermore, while the acquisition of Pharmasset has subsequently been validated by the singular – and staggering – commercial accomplishments of the Sovaldi/Harvoni franchise, in the case of Kite, success will be determined by multiple factors, including whether CAR-T is effective in solid tumours, whether side effects can be effectively managed in the long term and whether the company's investment in allogeneic (i.e. 'off the shelf' CAR-T therapies) can allow Kite to catch up and overtake rivals in this approach.  

That said, looking back to some of the scepticism that surrounded the Pharmasset acquisition, one conclusion is clear; both deals are bold – ViewPoints: Gilead makes its long-awaited splash in oncology.

See alsoSpotlight On: Buysider thinks Kite deal may presage battle for bluebird bio


ESC in focus

There were a number of highly anticipated data readouts at this week's European Society of Cardiology (ESC) congress in Barcelona, including results from Novartis' Phase III CANTOS trial, showing that canakinumab demonstrated a 15-percent reduction in the risk of major adverse cardiovascular events (MACE) in certain patients who have had a prior heart attack.

While the data support the theory that targeting inflammation could help decrease cardiovascular risk, detailed results from CANTOS (which were previously top-lined earlier this year) suggest that Novartis may face some challenges in translating data into commercial success, one KOL told FirstWordViewPoints: CANTOS details add to wealth of scientific – but not necessarily commercial – intrigue.

SeeKOL Views Results: Leading cardiologist says Novartis has tough task turning canakinumab from breakthrough science experiment into commercial success

Bayer and Johnson & Johnson also shed further light on previously top-lined data shown to be overall positive, but with some caveats; in this case, relating to the Phase III COMPASS trial assessing the combination of Xarelto and aspirin (versus aspirin alone) in reducing the risk of major cardiovascular events in patients with stable coronary and/or peripheral artery disease (CAD/PAD). While the combination met both its primary and combined secondary efficacy endpoints, an increased bleeding risk is likely to act as a barrier in driving adoption, suggest 65 cardiologists we snap-polled this week.

FirstWord will be speaking to a leading KOL in the next few days about the COMPASS data – KOL Views: Xarelto’s ceiling in CAD and PAD – high, very high or sky-high?

Having announced positive, but played down, top-line results from the REVEAL study in June, Merck & Co. revealed that its CETP inhibitor anacetrapib reduced the risk of major coronary events by 9 percent relative to placebo. With the study powered to show a 15-percent reduction, however, analysts believe it unlikely that the drug will be filed with regulators – ViewPoints: With anacetrapib results about as bad as expected, Merck & Co.'s got little to lose.


Eli Lilly gets regulatory reprieve for Olumiant

Positive news for Eli Lilly this week, with the company confirming that it plans to resubmit the JAK inhibitor Olumiant (for the treatment of rheumatoid arthritis) before the end of January 2018, which is notably sooner than was expected. The announcement follows recent conversations between Eli Lilly and the FDA, and confirmation by the agency that data from an additional study will not be necessary to support a new application; although new efficacy and safety data will be included in the regulatory package submitted.

Lack of a protracted delay for Olumiant is a positive development for the JAK inhibitor class at large, although rheumatologists recently polled by FirstWord suggested there was likely to be minimal negative read across from Eli Lilly's regulatory snaffle to utilisation of Pfizer's Xeljanz, which is currently the only marketed JAK inhibitor – Physician Views: Xeljanz more compelling than Olumiant for psoriatic arthritis; Olumiant delay likely to have neutral impact on Xeljanz use in RA.

Share price reaction to Eli Lilly's earlier suggestion (in July) that Olumiant would be resubmitted no earlier than late 2018 also indicates that investors have high hopes of the JAK inhibitor market. This opportunity could be particularly pertinent given that Eli Lilly's GLP-1 agonist Trulicity looks set to face considerable competition in the diabetes market from Novo Nordisk's semaglutide, according to endocrinologists – Physician Views Poll Results: Trulicity appears to have a semaglutide-sized problem.


Did AstraZeneca look to acquire Daiichi Sankyo for $16 billion last year?

According to rumours they did before Daiichi Sankyo denied the claims on Thursday; but not before chatter sent the Japanese company's share price up as much as 13 percent.

While a deal could make some sense – Daiichi has scale in oncology and some interesting cancer R&D focused on armed antibody targets – the tables may have turned in recent months. Following confirmation that the MYSTIC study failed to hit its initial progression-free survival endpoint, suggestions have grown AstraZeneca is more likely to be targeted itself.

Data presented at next week's European Society of Medical Oncology (ESMO) congress in Madrid – which FirstWord will be attending – including results from both the PACIFIC and FLAURA studies, should help to provide AstraZeneca investors a better idea of the company's growth outlook (ViewPoints: Can AstraZeneca mount a recovery at ESMO?).

There is also likely to be a strong focus on the PARP inhibitor class at ESMO, which could shed further light on the pros and cons of AstraZeneca's recently announced Lynparza collaboration with Merck.

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