Put through its paces properly, can remdesivir become pharma’s launch pad for a COVID-19 response?
Following weeks of speculation and mixed data from small uncontrolled studies Gilead Sciences’ antiviral agent remdesivir has been shown to accelerate the recovery time of hospitalised patients with advanced COVID-19 by 31%. Importantly these data come from a double-blind placebo-controlled Phase III study led by the US National Institute of Allergy and Infectious Diseases (NIAID).
Remdesivir is no magic bullet and its availability will not radically change the approaches being taken by governments around the world to slow the spread of COVID-19. The data show no significant mortality benefit, though numerically trend in favour of remdesivir. Recently published data from a study conducted in China, which was blinded and placebo-controlled but terminated prematurely due to insufficient enrolment, did not show a significant benefit in favour of remdesivir. One argument is that the NIAID study may have enrolled less severe patients.
Nevertheless, the newest data represent an initial response by the pharmaceutical industry which can hopefully be built upon in the coming months. Suggesting that remdesivir should now be considered the standard of care for relevant patients, NIAID director Anthony Fauci described the study as offering "a very important proof-of-concept because it has proven that a drug can block this virus."
The COVID-19 vaccine race gathers pace
Against this backdrop the development of an effective vaccine for SARS-CoV-2 remains imperative and first quarter earnings season provided an opportunity for a number of companies to outline the approaches they are taking.
Sanofi and Merck & Co., both established vaccine players, preached caution towards the aggressive development timelines being discussed by some smaller and less experienced developers which have helped to fuel speculation that limited doses of a vaccine could be available in late 2020.
Sanofi CEO Paul Hudson suggested that challenges in up-scaling the manufacture of novel vaccines, particularly those using newer approaches such as mRNA, are being overlooked. As one of the only companies capable of delivering required scale Sanofi says it will be able to manufacture one billion doses of its most advanced vaccine candidate by mid-2021, when it anticipates potential approval.
Merck’s R&D head Roger Perlmutter stressed that more than one vaccine may be required to inoculate the world’s population. Yet to provide much detail about its programme, Merck will approach the challenge ahead with "enthusiasm but also with humility," Perlmutter said.
Pfizer is developing four mRNA vaccine candidates with BioNTech and has moved the first of these into human testing this week. If successful, Pfizer believes it will be capable of delivering "hundreds of millions of doses," next year but suggested initial production could start before the end of 2020 to facilitate emergency access for healthcare professionals and other at-risk groups.
A team from Oxford University in the UK also says it could be on track to deliver a vaccine this year. On Thursday it signed a deal with AstraZeneca for the further development, large-scale manufacture and potential distribution of the vaccine; an intriguing development given the promise this vaccine reportedly holds and AstraZeneca's lack of experience in the vaccine field.
Pharma confident of riding out the COVID-19 storm over the course of the year
First-quarter earnings season has also provided investors a first opportunity to assess how the COVID-19 pandemic has impacted pharma’s revenue and operating performance. A majority of companies have reported an increase in sales driven by pre-lock down stockpiling, which they expect to be offset over subsequent quarters by the negative impact of social distancing measures.
The broadly held view among senior industry executives is for a return to relative normality for the pharmaceutical industry in the second half of 2020, meaning that nearly all have maintained their full year guidance at this point.
Merck & Co. is the notable exception, choosing to cut its full year guidance by $2.1 billion. The company justified its caution by describing greater exposure to COVID-19 headwinds amongst its peers. Two-thirds of its pharma products require administration by a healthcare professional, said Merck, whilst its presence in the animal health market, which is expected to recover at a slower pace, will also provide a drag on full year performance. On a more positive note, on Tuesday Merck received FDA approval for a six-weekly, 400mg dosage of its key cancer treatment Keytruda for all approved adult indications. Use of this dosing regimen will allow patients to be treated less frequently.
AstraZeneca's first quarter results were also watched closely given the company's notable presence in China. Despite the earlier impact of COVID-19 in China AstraZeneca said its sales here grew by 14% year-on-year in the first quarter, noting that key brands which experienced a decline in revenues have quickly begun to recover. A promising sign for the months ahead in other markets perhaps.
New drug news of note
Away from COVID-19 a number of potentially significant clinical and regulatory updates have been announced over the past week.
Sanofi presented promising Phase II data for its oral BTK inhibitor SAR442168 in relapsing multiple sclerosis, suggesting that if pivotal-stage is similarly impressive the drug could usher in a second oral treatment revolution for the disease.
In collaboration with its partner Regeneron, Sanofi also provided an update on its PD-1 inhibitor Libtayo for the first-line treatment of metastatic non-small-cell lung cancer (NSCLC). A study in patients with high levels of PD-L1 has been stopped early after Libtayo was shown to significantly prolong overall survival (OS). Merck & Co.’s Keytruda is likely to remain the dominant player in this market by some margin, say experts, but with Libtayo continuing to impress Regeneron and Sanofi remain in the game.
AstraZeneca and Merck’s PARP inhibitor Lynparza has been shown to prolong overall survival in a subset of prostate cancer patients, the former announced this week. Subsequent publication of data from the PROfound trial in the New England Journal of Medicine (NEJM) on Tuesday showed that in patients with faulty BRCA1, BRCA2 and ATM genes Lynparza extended survival by an average of 19 months versus 15 months for patients who received the targeted hormone treatments abiraterone or enzalutamide. AstraZeneca estimates that around 25% of men with advanced prostate cancer will be eligible for treatment with Lynparza.
Roche announced new data for its experimental spinal muscular atrophy (SMA) treatment risdiplam this week showing that the drug met its primary endpoint in a study of infants with type 1 disease. Results from Part 2 of the FIREFISH study confirm efficacy previously seen in Part 1 of this trial and provide further clarity on why the FDA’s regulatory review of risdiplam was extended from May to August. These data have recently been submitted to the agency and support the case for broad approval for patients with type 1, 2 and 3 SMA.
Boosting its aspirations in the oncology market GlaxoSmithKline secured expanded US approval for its PARP inhibitor Zejula on Wednesday to include maintenance treatment of women with ovarian cancer, who have responded to chemotherapy, irrespective of biomarker status. AstraZeneca and Merck are seeking approval for the combination of their PARP inhibitor Lynparza with Avastin in the same setting with a regulatory decision expected within the next two months. As a monotherapy Lynparza is approved as a first-line maintenance therapy for the approximate 20% of ovarian cancer patients who are BRCA positive.
AACR, Take 1
The American Association for Cancer Research (AACR)'s annual meeting- at least the first of its two virtual meetings- was at risk of begin swept under the rug in 2020, though a few disclosures managed to rise above the COVID-19 noise.
An investigator-sponsored study of Iovance Biotherapeutics' tumour-infiltrating lymphocytes (TILs) in non-small-cell lung cancer pointed towards a strengthening efficacy profile for the cell therapy. The AACR data added two new complete responses to the dataset for TILs, with responses ongoing for nearly one year - strengthening the profile of the cell therapy that still has plenty of sceptics. However, those sceptics may have won the day as Iovance's share price dropped off post-AACR, with investors needing more patients and longer follow-up to sign on in the big-ticket indication.
Another AACR disappointment came from Verastem Oncology, which had positive data from its combination of kinase inhibitors in non-small-cell lung cancer. The company saw only one in ten patients respond to a combination of VS-6766 and defactinib - with that response rate skyrocketing in patients carrying a KRASG12V mutation. That constraint to a less popular- and less prevalent- version of everyone's favourite oncology target led to a nose-dive in the company's share performance this week. ViewPoints: Verastem settles in on an unexpected KRAS.
But in better news, data from Syndax Pharmaceuticals was able to lift both its share price and the expectations for menin as a novel leukaemia target. The company's candidate managed to produce responses in two of three amenable leukaemia patients in its Phase I trial, while still on the low end of its dose-escalating study. The rising tide of proof of concept for the new target also lifted the boats at Kura Oncology, which started a Phase I study of its own menin/MLL1 inhibitor last year. ViewPoints: AACR unveils new leukaemia race for Syndax, Kura.
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