Novartis spotlights "wild card" assets, key growth drivers at R&D event

During its annual investor day presentation on Tuesday, Novartis unveiled five experimental "wild card" treatments covering a range of drug classes and medical conditions that the company says offer "high-risk, high reward" opportunities in the years ahead. The R&D meeting also highlighted multiple mid- to late-stage assets with more steady prospects that have milestones coming up, several in the next year or two, as well as potential new indications for existing products Entresto (sacubitril/valsartan), Cosentyx (secukinumab), Kisqali (ribociclib), Piqray (alpelisib) and Beovu (brolucizumab).

"Our rich pipeline continues to advance, and we highlight many assets that show significant promise," remarked CEO Vas Narasimhan. According to the company, the total value of estimated sales of products launched from 2020 to 2026 puts Novartis "as number two for pipeline replacement power in the global pharmaceutical industry."

'Wild card' assets

The "wild card" programmes include CSJ117, which is currently recruiting a Phase IIb study in patients with severe uncontrolled asthma. The neutralising antibody fragment directed against the epithelial-derived cytokine TSLP is designed to be delivered via a dry-powder inhaler directly into the lungs.

Meanwhile, ECF834 and QBW251 are being developed as potential treatments for dry-eye disease and chronic obstructive pulmonary disease (COPD), respectively, with Phase IIb readouts for both anticipated in the second half of 2021. Novartis in-licensed ECF834 from Lubris in 2017, saying the recombinant human lubricin protein had shown evidence of being able to provide instant relief of symptoms, and improvement in signs of dry eye within 28 days. In regards to QBW251, Novartis noted that the oral CFTR potentiator enhances mucus clearance and reduces pulmonary infections, potentially leading to "life-altering improvements" for COPD patients.

In addition, a Phase IIb trial of LNA043 in osteoarthritis is slated to begin next year as well. According to Novartis, the modified human ANGPTL3 compound may be able to repair damaged cartilage when administered as an intra-articular injection. Finally, the Swiss drugmaker also highlighted NIS793, a monoclonal antibody licensed from XOMA and designed to treat solid tumours by inhibiting the TGF-beta pathway and modulating the tumour microenvironment. The first patient was dosed in a Phase II study last month in metastatic pancreatic cancer, and the trial is expected to be completed by August 2022.

Steadier prospects

Other mid- to late-stage assets with upcoming milestones include iptacopan, an oral factor B inhibitor that is expected to advance to Phase III testing for IgA nephropathy in the first half of 2021. In addition, Phase III study results for the next-generation anti-IgE antibody ligelizumab in chronic spontaneous urticaria are expected in the second half of 2021, with regulatory submission slated for the year after that. Novartis noted that Leqvio (inclisiran), an siRNA that inhibits translation of PCSK9, recently received a positive opinion from an EU advisory body to treat adults with hypercholesterolaemia or mixed dyslipidaemia, while a decision by US regulators is due next month. The company also said a Phase IIb study of small molecule RNA splicing modulator branaplam is planned to get under way in the first half of next year for the treatment of Huntington's disease.

Novartis highlighted some promising candidates in its oncology portfolio as well, including the anti-IL-1-beta antibody canakinumab in non-small-cell lung cancer (NSCLC), with final results from the Phase III from the CANOPY-1 and CANOPY-2 trials anticipated in the second and first half of 2021, respectively. The company noted that TNO155, an inhibitor of SHP2, is advancing in early clinical testing with a "broad combination strategy" for KRAS G12C mutant NSCLC and other solid tumours, while the selective B/C RAF inhibitor LXH254 is "making progress" in multiple combination studies in NRAS and BRAF mutant melanomas and in certain forms of lung cancers. Meanwhile, data from the Phase III VISION trial for 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer are expected in the first half of 2021, while a possible submission for the anti-TIM-3 monoclonal antibody sabatolimab in high-risk myelodysplastic syndrome could come in the second half of next year.

New indications for existing drugs

Meanwhile, Novartis said it is "advancing sustained lifecycle management" for many existing products, with a focus on five key programmes. Entresto, which is already approved in the US and Europe for patients with certain forms of heart failure (HF), is under review for the treatment of HF patients with preserved ejection fraction, with an FDA decision expected in the first quarter of 2021. Expanded label submissions are also planned next year for Beovu in diabetic macular oedema, and for alpelisib in PIK3CA-related overgrowth spectrum, the latter already sold under the brand name Piqray to treat certain types of breast cancer. Meanwhile, Novartis said it is awaiting Phase III findings in the second half of next year for Cosentyx in hidradenitis suppurativa, as well as overall survival data from the MONALEESA-2 trial of Kisqali in treatment-naïve postmenopausal women with HR-positive, HER2-negative breast cancer.

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