Undeterred by another unconvincing performance, this time in the Solidarity trial, US regulators have granted Gilead’s Veklury full approval with a remarkably generous label. The antiviral is indicated for any hospitalised Covid-19 patients over 12, despite very weak evidence of benefit in those deemed modestly ill. The FDA defended its apparent dismissal of the Solidarity trial in an FAQ sheet, describing it as an open-label study of mortality benefit – none was found – while ACTT-1, on which Veklury’s approval was largely based, was a “rigorously” designed assessment of time to recovery. Raymond James analysts point out that the FDA also chose to ignore two negative Chinese trials. Still, postmarketing requirements suggest that the regulator has an eye on a post-pandemic world, once political scrutiny of its actions has lessened. Whether full approval will mean greater use of Veklury is a separate question. Gilead’s stock opened 3.5% higher today, indicating that investors believe so, though physicians will perhaps be less easily swayed by a broad label. All eyes now turn to Gilead’s earnings next week, when recent demand will be scrutinised, to see if the sellside’s blockbuster sales forecasts can be met. Consensus for third-quarter sales sits at around $800m.

The latest safety alert to hit Covid-19 research efforts seems to be benign: it has been widely concluded that the death of a participant enrolled in the Brazilian trial of Astrazeneca and Oxford University’s Covid-19 vaccine, news of which emerged yesterday, was unrelated to the project, AZD1222. But future scares should be expected, simply because such huge numbers of trials of experimental agents are ongoing. Commercial companies are sponsoring almost 300 Covid-19 trials of agents that have yet to reach the market in any use, seeking around 300,000 volunteers in total, Evaluate Vantage estimates. Massive vaccine studies account for a big proportion of that enrolment number; take these out and that still leaves more than 60,000 people potentially being exposed to unapproved agents. Add in academic-led trials and those testing repurposed drugs, and the trial count quickly climbs into the thousands. At least the various halts show that safety monitoring systems are functioning. US trials of AZD1222 are due to restart this week, according to reports, while Johnson & Johnson’s vaccine candidate and Lilly’s antibody remain under review.

With generic competition eating into sales of Tecfidera, and the follow-on project Vumerity missing analyst forecasts, Biogen’s fate is tied ever closer to its Alzheimer’s candidate aducanumab. At least six biosimilars to Tecfidera are on the market, the company said on a conference call today, and third-quarter sales of the MS therapy were down 15%, forcing the group to cut its overall 2020 guidance. In July, before the launch of the first Tecfidera generic, the company's 2020 sales were pegged at $13.8-14.2bn; this now stands at $13.2-13.4bn. Elsewhere, Biogen discontinued its anti-Lingo-1 multiple sclerosis project opicinumab following its failure in the phase II Affinity trial; the project had already flunked the Synergy study. Sales of Biogen's spinal muscular atrophy therapy Spinraza are drifting too, down 10%. Everything now hinges on the approval of aducanumab, and Biogen's decision today to buy back nearly $5bn of its own stock rather than doing transformative M&A will be seen as unimaginative. The FDA adcom on November 6 is more crucial than ever.

It might come as a surprise that Merck & Co is developing a Yervoy competitor, but the group’s own CTLA-4 inhibitor, now called quavonlimab, is an important asset. At last week’s IASLC North America conference a phase I first-line NSCLC study of quavonlimab plus Keytruda was at last updated, showing a handful more subjects versus what had been disclosed at Esmo 2018, but importantly revealing survival data too. Of course this trial had no Keytruda-only cohort, so the only logical comparison is versus Keynote-042, which backs the monotherapy’s US approval in front-line NSCLC patients expressing PD-L1 at ≥1%. While the latter cites median OS of 16.7 months in these PD-L1 expressers, the quavonlimab combo has now shown 18.1 months in all-comers at its phase II target dose of 25mg every six weeks – albeit at the expense of 30% of patients reporting treatment-related adverse events. It is now essential to watch the Keynote-598 trial, ending in February 2023 and testing Keytruda plus Yervoy versus Keytruda in first-line NSCLC. Merck stands to win both ways: if Yervoy shows no added benefit a competitor has been beaten, but if it does Merck has quavonlimab waiting in the wings.

Data are to come next week on Mirati’s adagrasib, and if the group is to maintain its monster valuation of nearly $9bn it cannot afford to disclose any diminution of the Kras G12C-selective inhibitor’s effects. Adagrasib, formerly known as MRTX849, will be the subject of two presentations at the Triple (EORTC-NCI-AACR) meeting. LBA-03, revealing updates in NSCLC, is a plenary; LBA-04 covers colorectal cancer and other solid tumours. So far adagrasib seems to have the edge over its main competitor, Amgen’s sotorasib, but with far lower patient numbers. And response rates with sotorasib in NSCLC dwindled on central review, from around 54% a year ago to 35% last month, something Mirati will be keen to avoid. Amgen plans to file on its phase II data, but Mirati has not yet made its filing intentions plain; the group is planning an investor event after the presentations on October 25 at which it might address this issue. Mirati will also use its investor meeting to reveal plans for MRTX1133, another Kras inhibitor but this time selective for G12D, a mutation Mirati says is relevant in a greater number of patients than G12C.

Fuelled by Covid-19, Roche’s diagnostics sales are doing nicely – which is just as well, because biosimilar competition for some of its major blockbusters has taken a toll on the Swiss group’s drug sales. Its oncology franchise is down 8% owing to biosimilars and the effects of the pandemic, and despite Roche talking up its newer drugs such as Tecentriq and Perjeta it is clearly suffering in this area. Phase I discontinuations also bear examination. Roche has canned RG6000, a dual leucine zipper kinase inhibitor for amyotrophic lateral sclerosis, the only molecule with this mechanism known to have been in development by any pharma group. An antibody-drug conjugate to treat Staphylococcus aureus infections, RG7861, has also been dropped; this had resulted from a 2011 research collaboration into ADCs with Seagen. Overall Roche’s pharma division brought in SFr34.3bn ($37.5bn) in the first three quarters of 2020, down 1% on a constant-currency basis. But sales in its diagnostics unit were up 9% at constant currency at SFr9.6bn for January to September. Roche has launched 13 separate Covid-19 assays in various territories, and doubtless has further ones planned. 

Botox’s almost complete domination of the neuromuscular blocking agent market has held off a couple of rivals; however, its new owner, Abbvie, might soon face a bigger challenge. Revance Therapeutics’ daxibotulinumtoxinA has been designed to be longer acting, and the first pivotal results in a medical setting seem to confirm this. The Aspen 1 trial in cervical dystonia found a median duration of response of 20-24 months; according to a cross-trial comparison put together by Revance, Botox wears off around six weeks sooner. This was a secondary measure of Aspen, which pitted two doses of daxi against placebo; the primary endpoint, change on a symptom score, was cleared with statistical significance. The inclusion of a Botox cohort would have made these findings more interesting, of course, although Revance’s reluctance to go head to head is understandable. The real battle will take place in the market, and Revance would not have wanted to risk handing an unwanted finding to Abbvie’s sales team. Revance needs to build a picture of a long-acting and safer option, and several trials due to report next year could help. The next hurdle is FDA approval, due next month in glabellar lines.

Not daunted by GB001’s blow-up in its phase II studies in asthma and chronic rhinosinusitis, Gossamer Bio has decided to push ahead with a phase III programme in the former indication – and to find a partner to pay for it. The Leda trial missed its primary endpoint of asthma worsening; on a conference call management attributed the lack of a dose-response to the prostaglandin D2 receptor antagonist achieving near-total receptor blockade at even the lowest dose, though of course this hardly explains the endpoint miss. Stronger responses in a subgroup found in a post-hoc analysis seem to be the trigger to push on, although executives failed to precisely characterise patients in the subgroup. Gossamer wants to begin a 12-month phase III trial with either the 20mg or 40mg dose. The sellside also found reasons for cheer: Leerink analysts noted that the exacerbation data “look good” and insisted Gossamer shares still look a “better buy than a sell”. Given the utter failure of other DP2 inhibitors in asthma all of this seems incredibly optimistic; even the 37% fall in the group’s share price is somewhat surprising, as GB001’s miss in Leda might have been expected.

A Covid-19 diagnosis first this week has come as a result of different approaches and technologies converging. Quidel has gained US FDA authorisation for the first test for both the coronavirus and flu that works by detecting viral antigens rather than RNA. Nicknamed the ABC test because it tests for influenza A and B as well as Covid-19, the Sofia 2 Flu + Sars Antigen assay detects the nucleocapsid protein from the three viruses in a single nasal swab. It may be used at the point of care, returning results inside 15 minutes, and Quidel claims impressive accuracy, as shown below. With Covid-19 cases on the rise in many countries and the flu season getting under way in the Northern hemisphere, this kind of combination test could help save money. Quidel was the first company to gain authorisation for an antigen test for Covid-19 in mid-July. Another antigen test, this time developed by New Jersey-based Access Bio, was also authorised last week. Access now has the FDA’s rubber-stamp for all three main types of Covid-19 tests, its molecular and antibody assays having been authorised in July.

Note: "other" includes six antigen tests, three home sampling kits and two IL-6 tests.
 

Sometimes medtech acquisitions are prompted when groups consolidate as a defence against difficult market conditions; Smith & Nephew’s purchase of Integra Lifesciences’s extremity implants last month was arguably one such. But sometimes the opposite occurs, with a buyer targeting technologies in high demand. Steris’s swoop on Key Surgical for $850m is one of the latter. Part of Chicago-based investor Water Street Healthcare Partners’ portfolio, Key Surgical is, like its new owner, focused on sterilisation. It offers devices used in operating theatres as well as protective equipment such as face shields, masks and gloves, for which there is an obvious and pressing need. Financed with debt and cash, the deal is set to close by the end of the year and be accretive to top-line growth, margins and earnings, Steris says, with Key Surgical expected to see revenue of around $170m and adjusted EBIT of $50m this year. The deal also comes with an tax benefit which ought to reduce the effective purchase price to around $810m. More pandemic-inspired deal-making might be welcomed by bankers: though the Key Surgical acquisition is worth less than $1bn it is still the fifth biggest announced so far this year.