Friday Five - The pharma week in review (11 September 2020)

Uncertainty envelops COVID-19 vaccine hopeful

The race to develop a COVID-19 vaccine hit a potentially significant speed-bump this week when it was confirmed that a Phase III study evaluating the candidate being co-developed by AstraZeneca and the University of Oxford (AZD1222) has been put on hold due to a potential safety issue. It also emerged that the trial was temporarily paused in July, though quickly restarted when the neurological issue in question was deemed to be unrelated to the vaccine.

On Wednesday, it was subsequently confirmed by AstraZeneca CEO Pascal Soriot that the latest hold was triggered by one vaccine recipient in the UK developing symptoms consistent with the spinal inflammatory disorder transverse myelitis. Diagnosis has yet to be confirmed, but the patient was due to be discharged from hospital imminently, said Soriot. The nature of how this information was disclosed threatens to raise some controversy, however, as Soriot was speaking to a small number of investors on a conference call organised by the investment bank JP Morgan.

To what extent potential links to a case of transverse myelitis could shape future development of AZD1222 or other COVID-19 vaccines is unclear at this point and a committee of independent experts will decide whether the Phase III study can resume. A best-case scenario for future vaccine development would require the symptoms identified to be the result of an underlying immune system issue in the patient in question. The study did include exclusion criteria for enrolees with known immunosuppressant issues, though it is far from unprecedented for large clinical studies to be paused like this.

Vaccines being developed by BioNTech/Pfizer and Moderna are based on mRNA technology so are less likely to be the subject of any potential read across from events related to AZD1222, though mRNA is a novel approach to vaccine development which warrants some caution. Johnson & Johnson and Cansino, however, are both developing vaccines which like AZD1222 use an adenoviral vector, albeit in both instances use a human adenovirus whilst AZD1222 utilises a chimp vector.

Speaking during an online event on Thursday, Soriot reiterated that it remains unclear how long the Phase III study will be paused for, but said he was hopeful the vaccine could still be submitted to regulators and approved by the end of 2020.

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Vaccine developers pledge scientific integrity

Earlier in the week, Soriot was one of nine chief executives whose companies are developing COVID-19 vaccines to issue a joint statement pledging to "uphold the integrity of the scientific process" and make "the safety and well-being of vaccinated individuals our top priority." The pledge was issued amid growing suggestion of political pressure on the FDA to authorise a vaccine as soon as possible (see Friday Five - The pharma week in review (4 September 2020 and Warp Speed head vows to quit if pressured to rush out a COVID-19 vaccine).

In addition to Soriot, the CEOs of BioNTech, GlaxoSmithKline, Johnson & Johnson, Merck & Co., Moderna, Novavax, Pfizer and Sanofi said they will "only submit for approval or emergency-use authorisation after demonstrating safety and efficacy through a Phase III clinical study that is designed and conducted to meet requirements of expert regulatory authorities such as [the] FDA." The drugmakers noted that the agency "has established clear guidance for the development of COVID-19 vaccines and clear criteria for their potential authorisation or approval in the US." More here.

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Big Pharma interest in CD47 gathers pace

Once Gilead Sciences had announced in April plans to spend $4.9 billion to acquire the biotech company Forty Seven, it was always likely that other large-cap drug manufacturers would pile into the anti-CD47 space (CD47 is a clinically validated cancer immunotherapy target described as eliciting a 'don’t eat me' signal).

Gilead has paid a sizeable premium to access the most advanced asset in development and get a potential leg-up on what is an increasingly competitive field.

This week, AbbVie agreed to pay $180 million upfront for an exclusive license to co-develop I-Mab's Phase I anti-CD47 asset lemzoparlimab in multiple cancers and potential development of future CD47-related therapeutic agents, later confirmed to be bi-specific monoclonal antibodies. The agreement is potentially worth an additional $1.7 billion to I-Mab, making it the largest pharma out-licensing deal secured by a Chinese biotech company. More here.

Elsewhere, Pfizer made a $25-million equity investment in Trillium Therapeutics on the same day that the biotech announced very early, but highly promising, data for its two most advanced CD47 assets, triggering speculation that Trillium could be the next company in this space to secure a lucrative licensing deal or acquisition offer.

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Another BTK inhibitor moves into late-stage MS testing

Sanofi has spent a lot of time talking up the potential of its investigational multiple sclerosis treatment SAR442168, an oral BTK inhibitor that moved into Phase III studies earlier this year. More recently it put its money where its mouth is by acquiring the drug’s discoverer, Principia BioPharma.

The caveat is that Sanofi desperately needs a big new drug launch over the next few years to support CEO Paul Hudson's ambition of reinvigorating its R&D pipeline.

It's some good news then that Roche has confirmed the initiation of Phase III studies for its own BTK inhibitor fenebrutinib. The Swiss company has emerged as an important new player in the MS market thanks to the successful launch of its anti-CD20 therapy Ocrevus and would appear to be taking the threat from Sanofi seriously.

In the meantime, Ocrevus faces more immediate competition from another established MS player in the form of Novartis' recently approved Kesimpta.   

See – Physician Views: Are neurologists ready for Novartis' Kesimpta?

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Gene therapies attract further scrutiny from regulators

The FDA's decision last month to issue a complete response letter (CRL) to BioMarin's regulatory application for the investigational haemophilia A treatment valrox raised two interconnected questions; was the agency concerned specifically with the clinical data submitted for valrox or has it chosen to take a more cautious approach towards gene therapies in general?

Three weeks down the line, and despite some speculation (see KOL Views Results: Leading expert says FDA’s rebuff of BioMarin’s valrox raises bar for gene therapy – perhaps beyond haemophilia A), there is no clear answer.

Events this week do not help. BioMarin now faces a similar delay to approval in Europe with regulators there requesting additional findings from an ongoing study, though not the same data as the FDA.

Meanwhile, Sarepta announced on Wednesday that the start of a Phase III study to evaluate its Duchene muscular dystrophy (DMD) gene therapy SPR-9001 has been delayed following a request from the FDA's Office of Tissues and Advanced Therapies (OTAT) that the company use an additional potency assay for SPR-9001 commercial process material before dosing in clinical trials. Analysts at Credit Suisse noted "we see possible further short-term weakness on timeline uncertainty, rising investor wariness about the FDA's approach to the gene therapy regulatory process (particularly following BioMarin's CRL in August) and risk that Sarepta may see its first-mover advantage in the field of micropdystrophin gene therapy versus competitor Pfizer diminish."

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