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Friday, February 1, 2019

Novartis eyes blockbuster launches for 2018-20, including Kymriah

As Novartis shakes off its Alcon eye business and the loss of two high-profile executives, chief Vas Narasimhan has outlined the Swiss drugmaker’s roster of 14 blockbuster launches, a bulk of which are expected to win approval between this year and 2020. The drugs included in the list are largely familiar, but the inclusion of the company’s pioneering CAR-T therapy Kymriah, whose adoption has been wobbly due to manufacturing woes, will raise some eyebrows.
In 2017, Novartis spent a hefty $9 billion on R&D, making it one of the top spenders in global biopharma. Investors expect to see the company to now get bang for its buck. Last November, the company used it R&D review to highlight 26 blockbuster contenders in its arsenal and offer a rosy picture of things to come after suffering a few knocks — the FDA rejecting its heart drug, and the company abandoning its attempt at a Rituxan copycat.
Since then, the company has seen good days and bad. On the positive front, its gene therapy for SMA secured the FDA’s priority review, and its sickle cell drug won breakthrough therapy status. The drugmaker also swallowed a cell and gene therapy manufacturer in an attempt to unclog the commercial rollout for Kymriah. In a first for a multinational pharmaceutical company, Novartis’ Sandoz unit tied up with Canadian medical cannabis producer Tilray, a landmark endorsement of the controversial plant. On Wednesday, as part of its full-year 2018 results, the drugmaker said four newer products — including Cosentyx and Entresto — in its roster of medicines achieved blockbuster status in 2018.
On the other end of the scale, Novartis has also suffered a number of setbacks in the last quarter of 2018. For instance, its migraine drug Aimovig — billed as a blockbuster and partnered with Amgen — was refused endorsement by the UK’s NICE, months after the agency declined to give the nod for Kymriah. Two top executives — CAR-T chief David Lebwohl and oncology head Liz Barrett — also left the drugmaker to take top positions in small biotechs. And J&J dealt Novartis a blow when its psoriasis drug Tremfya beat the dominant Cosentyx in a head-to-head study.
2018
AIMOVIG — The migraine drug forms part of a new crop of biologics targeting the CGRP protein that transmits pain signals into the brain. The drug was the first to win approval in 2018, and within months rival treatments from Lilly and Teva were also given regulatory nods. All three have demonstrated similar efficacy and safety in trials. Like its rivals, the drug is priced at $575 per month and has been pegged as a potential blockbuster. Following the NICE setback, reports suggested Aimovig was excluded from pharmacy benefits manager CVS’ formulary in the United States. This will be a blow, but there are other PBMs on the block.
KYMRIAH — The pioneering CAR-T drug was FDA approved amidst great fanfare in 2017, and since then the FDA has expanded its use in the United States and the EC also approved the drug last August. NICE refused to endorse the pricey drug. Meanwhile, rivals such as Gilead’s Yescarta have emerged, and Kymriah sales have suffered due to manufacturing issues. In the fourth quarter, the drug generated a paltry $28 million. However, Novartis is doing its best to shore up manufacturing, having bought cell and gene therapy manufacturer CellforCure.
LUTATHERA — The cancer drug, which came with Novartis’ $4 billion acquisition of Advanced Accelerator Applications in 2017, paid off handsomely in early 2018 after the FDA gave it a quick OK. Novartis reported an 11% jump in oncology revenue in the fourth quarter, driven partly by Lutathera sales of $81 million.
2019
BYL719 — Otherwise known as alpelisib, the PI3K inhibitor nearly doubled progression-free survival in a third of patients with a hard-to treat form of breast cancer last October. Other drugs in this class, including Roche’s taselisib, have largely crashed and burned due to safety concerns.
MAYZENT — Expected to launch this year, the MS drug also known as siponimod is critical for the company as one of its top sellers Gilenya has generic competition looming. Company officials have previously described the drug’s data in glowing terms, and analysts have concurred, offering a $3 billion peak sales projection for the treatment.
RTH258 — The eye drug has been built up as a rival to Regeneron’s flagship blockbuster injection Eylea and CEO Narasimhan has gone so far as to say RTH258 is “consistently superior” to Eylea, after conducting retrospective analyses of late-stage data last year. Eylea has been untouchable for more than a decade, so it is up to Novartis to prove otherwise.
ZOLGENSMA — The gene therapy is currently under FDA review and the agency is expected to announce its decision in May. In its review posted in December, ICER suggested the Zolgensma — with a list price of $2 million — would offer more cost-effective benefit in the long run versus rival Biogen’s Spinraza. However, the Swiss drugmaker has suggested a price of $4 million for the curative therapy, which it acquired via a $8.7 billion takeover of AveXis, may be justified.
2020
COSENTYX — The psoriasis drug that became a blockbuster in 2016 is one of Novartis’ key drugs, and the drugmaker is working on expanding the IL-17A inhibitor’s market by including patients with psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondylarthritis (nrAxSpA). Pivotal data are expected later this year and, if positive, will be followed by a marketing application before the end of this year.
ENTRESTO — The medicine is another top seller for Novartis and is currently approved for HFrEF (formerly known as systolic heart failure) — in these patients the heart muscle does not contract effectively, reducing the level of oxygen-rich blood pumped into to the body. Initially a slow moving product hampered by physicians reluctant to adopt a new therapy and insurers who balked at its price, Entresto is now comfortably a blockbuster product. The drug is now under evaluation for HFpEF (also referred to as diastolic heart failure) — a now larger group of patients whose heart muscle contract normally but ventricles do not relax as they should during ventricular filling. Data from the trial PARAGON-HF are expected in the third quarter of 2019.
INC280 — Otherwise known as capmatinib, the MET inhibitor was licensed to Novartis from Incyte in 2009. Mid-stage data on the drug in certain patients with the most common form of lung cancer (NSCLC), presented last October, showed INC280 induced an ORR of 72% in treatment-naive patients and about 39% in previously treated patients. Novartis is expected to submit a marketing application later this year.
OMB157 — Other than the approved Gilenya and Mayzent — which is currently under review — ofatumumab (OMB157) is another drug Novartis is hoping to use in MS. The drug, already sold as Arzerra, has caused a number of problems for Novartis as a treatment for leukemia — the drugmaker was forced to pull it off the market outside the US as competition heated up. Novartis thinks it can repurpose the drug for MS, an indication for which it is currently being investigated in two Phase III studies.
PDR001 COMBO — PDR001, also called spartalizumab, is Novartis’ PD-1 inhibitor and is being tested in a number of cancers. A late-stage study testing the drug in combination with Novartis’ approved cancer drugs — Tafinlar and Mekinist — in patients with metastatic melanoma is ongoing.
QVM149 — The asthma drug is currently being tested against standard triple combination therapy in a late-stage study in uncontrolled asthmatics — the trial is expected to be completed this year.
SEG101 — Expected to launch in 2020, the sickle cell disease drug has secured the FDA’s breakthrough therapy designation earlier this month. After a delay in 2018, a marketing application for the drug is expected this year.

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