Friday Five – The pharma week in review (22 May 2020)

Moderna provides provisional, but promising COVID-19 vaccine data

Moderna reported positive interim data from a Phase I study of its vaccine candidate against SARS-CoV-2, with results showing that mRNA-1273 elicited neutralising antibody titer levels in all eight initial participants in the low- and mid-dose cohorts, reaching or exceeding levels generally seen in convalescent sera. Shares in the company jumped as much as 24% on the news. More here.

Whilst these results are promising, Moderna found itself in the spotlight for other reasons on the back of this announcement. Despite both the vaccine and this initial study being heavily funded by the US government, the company raised an additional $1.3 billion in equity this week through a secondary offering on the back of very limited data.

Furthermore, Moncef Slaoui, the former Moderna executive recently appointed to co-chair the White House's 'Operation Warp Speed' coronavirus vaccine project, said he would divest approximately $12.4 million worth of stock options he had retained in the company, reported CNBC. All incremental value accrued in recent days will be donated to cancer research, said a spokesperson for the Department of Health and Human Services.

Read ViewPoints: Moderna's vaccine data prompt global optimism and biotech scepticism

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AstraZeneca to start delivering Oxford vaccine in September

In related news, the team developing the SARS-CoV-2 vaccine ChAdOx1 nCoV-19 at the University of Oxford recently published a preprint of data from a viral challenge study in non-human primates, which was the subject of notable discussion this week.

Seven days after inoculation, the six animals saw reduced viral loads in lung tissue relative to three control animals; two of three control animals subsequently developed viral pneumonia, while none did in the ChAdOx1 nCoV-19 group. However, there was no reduction in viral load samples obtained from nose swabs and no reduction in viral shedding from the nose, suggesting that even vaccinated animals could continue to be contagious or symptomatic.

Evidence of protection against viral pneumonia is a positive signal, which points towards potentially preventing the worst manifestations of the disease and a leading cause of strain on health-care providers.  However, the data could be indicative of a model where COVID-19 is rendered less severe, rather than prevented altogether. That would mean that the vaccine acts more like a therapeutic than a preventative treatment, and could limit its ability to impact social distancing measures.

However, on Thursday, AstraZeneca – which is working worth the University of Oxford to develop, manufacture and distribute the vaccine – said it has concluded initial agreements to supply at least 400 million doses and has secured manufacturing capacity for one billion doses. First deliveries will begin in September 2020.

The company also announced that it has received funding of more than $1 billion from the US Biomedical Advanced Research and Development Authority (BARDA) to support development, production and delivery of the vaccine, which includes a Phase III trial with 30,000 participants.

Notably this BARDA’s fourth investment in a SARS-CoV-2 vaccine but the biggest by some margin following pledges of $456m to Johnson & Johnson, $400m to Moderna and $31 million to Sanofi.

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What can pharma do to boost biomarker testing rates?

Targeted therapies have become an increasingly important component for treating cancer, but a new poll of 72 oncologists run by FirstWord suggests that only six in every 10 patients who are potential candidates for personalised therapy are tested for biomarker status.

The challenge becomes more acute where specific tumour mutations are less common, such as in the case of Eli Lilly's recently approved drug Retevmo, which is indicated to treat RET-fusion positive non-small-cell lung cancer (NSCLC) and thyroid cancers. Eli Lilly notes that RET fusions have been identified in approximately 2% of NSCLC cancers, for example.

A similar drug is being developed by Blueprint Medicines, called pralsetinib, but echoing the feedback from our poll, a key opinion leader told FirstWord this week that "the biggest hurdle (faced by Eli Lilly) is going to be non-testing and inadequate testing rather than a competing drug."

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PARPs continue to expand their therapeutic reach

Patients with some types of cancer are more likely to be tested for biomarkers than others. Our new report on the expanded role of PARP inhibitors for the first-line treatment of ovarian cancer indicates, for example, that current levels of testing for BRCA mutations are higher on average than the overall rate of testing across all cancer types (see above).

That report has been fielded in response to recent FDA approvals that will significantly broaden the proportion of advanced ovarian cancer patients who respond to chemotherapy who can then receive maintenance treatment with a PARP inhibitor.

Previously, the approximate 20% of patients with BRCA mutations could receive treatment with AstraZeneca's Lynparza. The FDA has now approved the combination of Lynparza with Roche's Avastin for a broader cohort of patients who are HRD positive (approximately 50% of ovarian cancer patients, inclusive of BRCA mutations) and green-lighted use of GlaxoSmithKline's Zejula as a maintenance therapy regardless of biomarker status.

The expanding use of PARP inhibitors is also relevant to prostate cancer, where two notable approvals in the US market have occurred in the past week. Clovis Oncology's Rubraca became the first drug in class to be approved in prostate cancer last Friday, as a third-line treatment for BRCA mutation patients. However, closing the commercial window for Rubraca, Lynparza was approved this week as a second-line treatment in a broader cohort of patients identified as being HRR positive.

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Novartis' Zolgensma approved in EU

Novartis has now secured conditional EU approval for its spinal muscular atrophy (SMA) gene therapy treatment Zolgensma, it was confirmed this week. Novartis estimates that between 550 and 600 infants are born with SMA in Europe each year.

Though a regulatory decision by the European Commission has occurred somewhat later than expected, it may have been worth the wait for Novartis. The label includes use to treat all infants and young children with SMA Type 1 up to a weight of 21 kg, according to the approved dosing guidance. This would indicate  use in children up to the age of five versus Zolgensma's label in the US, which stipulates use in infants aged two years and younger.

Pricing, once disclosed, is certain to be a subject of interest and debate; Zolgensma is priced at $2.1 million for a single intravenous infusion in the US.

Novartis has activated its 'Day One' access programme in Europe, which is designed to ensure that the cost of patients treated before national pricing and reimbursement agreements are in place aligns with the value-based prices negotiated following clinical and economic assessments. The company noted that the programme features a number of options including retroactive rebates, deferred payments and instalment options, as well as outcomes-based rebates.

In the US market Zolgensma is likely to face a new competitor in the form of Roche’s small molecule drug risdiplam later this year. 

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