Hype versus hope? – Moderna unveils COVID-19 vaccine data
Moderna released detailed results from an ongoing Phase I study of its experimental COVID-19 vaccine mRNA-1273 this week, confirming that it induced immune responses in all 45 participants. These data were sufficient to propel Moderna into the top 20 most valuable bio-pharma companies based on market value; it is the only company on that list without a marketed product.
At this stage, however, the limitations of Phase I data provide no confirmation that mRNA-1273 provides durable immuno-protective effects.
The ability of mRNA-1273 to elicit neutralising antibodies appears to be broadly on par with data recently shared for BioNTech and Pfizer's mRNA vaccine candidate BNT162b1. However, the side-effect profile of Moderna's vaccine also warrants some scrutiny. A 100-mcg dose of mRNA-1273, administered by a prime and boost regimen, is being advanced into Phase III testing, with side effects in a higher 250 mcg dose (including severe fatigue and chills) appearing to play a significant role in shaping this decision.
Furthermore, the preferred 100-mcg dose cannot be considered particularly clean either, with matters complicated further by the initial Phase I data only including patients 55 and under. Only additional data, with Phase III development expected to commence in a matter of weeks, will reveal the potential role of mRNA-1273 in combating the pandemic – and whether bullish investors have got ahead of themselves.
Will AstraZeneca and Oxford provide an imminent breakthrough?
Elsewhere, it was confirmed that detailed Phase I results for AZD1222, the COVID-19 vaccine being developed by the University of Oxford and AstraZeneca, will be published in the Lancet early next week. On Wednesday, it was rumoured that positive results for AZD1222, described by one source as being "extremely positive," will be reported imminently.
The suggestion is that new data will show AZD1222 induces both an antibody and T-cell response, and is not associated with major side effects. With patients already being recruited into a Phase II/III study, and the suggestion that hundreds of millions of doses could be produced by October, confirmation of these rumours would enhance AZD1222's status as the vaccine front-runner.
Bearing in mind the valuation gains that Moderna and other biotech companies have achieved on the back of vaccine development, AZD1222's success could have broader implications, with AstraZeneca having previously confirmed that the vaccine will be provided to governments at cost price. Any commercial market for COVID-19 vaccines may be much smaller than many investors are anticipating.
GSK shrugs off safety concerns for belantamab mafodotin (for now)
GlaxoSmithKline looks well positioned to bring a breakthrough myeloma treatment to the US market, following positive FDA advisory committee assessment of belantamab mafodotin this week. Advisers to the US regulator voted 12-0 in favour of its clinical benefit outweighing ocular toxicity concerns for the treatment of myeloma patients who have received at least four prior therapies.
In pre-meeting briefing documents published late last week, the FDA highlighted ocular toxicity as a significant safety concern; one that could still limit potential future use of belantamab mafodotin in earlier-stage patients.
At this juncture, however, getting belantamab mafodotin across the regulatory finishing line is what matters most to GlaxoSmithKline. The company has well publicised intentions to become a key player in the global oncology market (having exited the space six years ago) and now appears on track to claim credit for bringing the first anti-BCMA myeloma treatment to market.
Roche bags Blueprint's pralsetinib
Roche announced this week that it has agreed to pay Blueprint Medicines $775 million upfront to in-license marketing rights for the RET inhibitor pralsetinib. Pralsetinib is currently awaiting US approval for the treatment of RET mutated non-small-cell lung cancer (NSCLC) and thyroid cancers, with a decision for the former indication anticipated before the end of the year.
If approved, pralsetinib will compete with Eli Lilly's RET inhibitor Retevmo, so Blueprint's need for a co-marketing partner in the US and to out-license marketing rights completely in Europe has been apparent for some time. Blueprint's head of corporate development Helen Ho told FirstWord that partnering with Roche will be "transformative" for the commercial prospects of pralsetinib, aided by technologies accessible through Roche's Flatiron Health and Foundation Medicine subsidiaries.
Last year, Roche became the first pharma company with annual R&D spend in excess of $10 billion, but has also shown a willingness to invest externally to strengthen its pipeline; it spent $1.7 billion to acquire Ignyta in 2017 (to gain access to another targeted cancer treatment – Rozlytrek) and $750 million upfront to in-license ex-US rights for Sarepta Therapeutics' experimental Duchene muscular dystrophy (DMD) gene therapy SRP-9001 late last year.
Tecentriq stumbles in ovarian cancer
The relatively new class of agents known as PARP inhibitors look well positioned to drive treatment practice change for first-line advanced ovarian cancer, after another setback for immunotherapy in this setting.
Roche announced this week that the combination of its PD-L1 inhibitor Tecentriq with the widely used pairing of Avastin and chemotherapy did not extent progression-free survival versus Avastin and chemotherapy alone.
Partners Merck KGaA and Pfizer previously announced that the combination of their PD-L1 inhibitor Bavencio with chemotherapy failed in both the first- and second-line settings, supporting the view that ovarian cancer is less suited to the utilisation of immunotherapy.
Two PARP inhibitors – AstraZeneca and Merck & Co.'s Lynparza, and GlaxoSmithKline's Zejula – have been approved as first-line maintenance treatments for ovarian cancer patients on the strength of impressive data. Immunotherapies are being evaluated in combination with PARPs, which now perhaps represents their best opportunity to show effectiveness in ovarian cancer.
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