Qiagen today became the third company to launch a T-cell-based test for prior Covid-19 infection and also to assess individuals’ response to vaccination. The Quantiferon Sars-Cov-2 assay, which detects CD4+ and CD8+ T-cell responses elicited by the virus, is now available in Europe, joining Perkinelmer’s T-Spot Discovery Sars-CoV-2 product. Neither of these is yet available in the US, however, where the only T-cell test with FDA emergency authorisation is Adaptive Biotechnologies’ T-Detect Covid assay. Qiagen says its blood test, which has grown out of the Dutch group’s year-old collaboration with Tscan Therapeutics, is differentiated from the competition as it does not require a purification step for the lymphocytes. Testing for Covid-19-reactive T-cells is believed to be a useful adjunct to antibody testing since the response declines more slowly than antibody response, but also appears beforehand, since CD4+ T-cells help B cells generate anti-Covid antibodies. Quantiferon Sars-Cov-2 could indicate how severe the course of a Covid infection will be, according to Qiagen, as well as how long immunity might last. But there is as yet no definitive evidence linking T-cell readings to resistance to subsequent infection with Covid-19. 

Novartis is hardly known for novel CNS projects. But today the group took a punt on a potentially disease-modifying mechanism for Parkinson’s, via a deal with UCB. The target, alpha-synuclein, has had its fair share of setbacks, with Roche and Prothena last year reporting mixed data with their antibody, prasinezumab, and Biogen this year discontinuing BIIB054. At least Novartis has not paid top dollar: the company is giving UCB $150m up front, although it is on the hook for up to $1.5bn in milestones. In return, the Swiss company gets global co-development and co-commercialisation rights to UCB0599, an oral, brain-penetrant alpha-synuclein misfolding inhibitor, and an option on UCB7853, an anti-alpha-synuclein antibody. The two projects could complement each other, UCB noted. As well as Roche and Prothena, which are pressing on with prasinezumab, other companies looking at this target include include AC Immune, which struck its own deal here in July. Annovis Bio’s ANVS401, meanwhile, inhibits amyloid-beta and tau as well as alpha-synuclein – that group is planning phase 3 trials in both Parkinson’s and Alzheimer’s, but phase 2 data have been far from convincing.

A narrow squeak through its adcom yesterday means Merck and Ridgeback’s Covid-19 pill molnupiravir is odds-on for US authorisation. Uptake is another question. The drop in efficacy from 50% at interim to just 30% at the final readout might render the drug a distant second, in terms of demand, to Pfizer’s far more effective-looking Paxlovid. Indeed, data presented yesterday showed that among patients assessed between the interim and final analysis, those given molnupiravir were more likely to suffer hospitalisation or death than those given placebo. As worrying as the sharp decline in efficacy was the inability of Merck scientists' to explain it, with one researcher telling the panel he did not have “a satisfying answer” to this question. Neither will the discussion of molnupiravir’s potential side effects have done Merck any favours. Embryo foetal toxicity seen in animal studies means the FDA could refuse to approve the pill for use in pregnancy, or at least recommend against its use. But there is one reason to expect molnupiravir, if authorised, to ramp acceptable initial sales: the US Government has already committed to spending $2.2bn on the pill by early 2022.

The FDA dished out three Pdufa extensions and four knockbacks in November, including a CRL for Beyondspring’s plinabulin in chemotherapy-induced neutropenia. Beyondspring said today that the FDA had requested a second clinical study of plinabulin; this news sent the company's shares down 55% in early trading and follows disappointing NSCLC data at Esmo. On the flip side, Biomarin’s Voxzogo gained accelerated approval in patients aged five and older with achondroplasia. Assessing final adult height is part of the post-marketing requirement and Biomarin has said it will use the ongoing open-label extension studies versus natural history for confirmatory data. Merck’s Keytruda also gained another string to its bow last month with an adjuvant approval in renal cell cancer. The decision came three weeks early and puts Keytruda further ahead of rivals, which will start reporting phase 3 data next year.

The story of TG Therapeutics’ Unity-CLL trial of its combo cancer project U2 has already taken several turns, encompassing design changes, delays and recently a surprise benefit. Yesterday the FDA added another twist, demanding an advisory committee that at the very least will delay U2’s approval. An approval decision had been due by March 25. The project comprises ublituximab plus Ukoniq, the former an anti-CD20 antibody also being developed in MS and the latter a recently approved PI3K delta inhibitor. The FDA wants the panel to review Ukoniq in its approved lymphoma settings but, more ominously, is concerned about a lack of survival benefit with U2 in Unity-CLL. The agency had requested an early analysis of OS from the trial, and found an imbalance favouring control with a non-significant hazard ratio of 1.23. This improved to 1.04 when Covid-related deaths were excluded, and TG stressed that the finding was preliminary, with the study not powered for OS. This clearly bodes poorly, however, and TG shares tanked 35% yesterday. Ublituximab’s potential in MS is considered TG’s biggest opportunity, and execs confirmed yesterday that the FDA had informally accepted this filing. Investors must hope that the agency’s concerns do not extend beyond oncology.

Olema was punished today for confusion about data with its sole project, OP-1250, with a 56% share price crash showing just how jittery the markets are for biotech stocks. It all started when data from a phase 1/2 dose-escalation study, due for presentation at the San Antonio Breast Cancer Symposium next week, were apparently leaked yesterday. Remarkably, the company later claimed the poster had been falsified and put out its own, slightly worse, results today. Olema plans to start phase 2 trials of ’1250, a complete oestrogen receptor antagonist and selective oestrogen receptor degrader, as monotherapy and in combination with a CDK4/6 inhibitor at the start of 2022. But the November 1 cut also showed that three patients had grade 4 neutropenia attributed to study drug by the investigator. Combination with CDK4/6 inhibitors will likely be necessary for future success, a class that is already associated with high rates of neutropenia, meaning this signal could also have worried investors. Still, even if the data did not warrant such an extreme reaction, the optics on the whole situation are terrible. This is a clearly a black mark against Olema, which was presenting its first results as a public company.  

Blueprint Medicines' ability to make a success of LNG-451, a preclinical EGFR exon 20 inhibitor it obtained yesterday via its $250m purchase of Lengo Therapeutics, depends on a number of other projects failing. Aside from the two bispecifics already approved for this particular lung cancer niche there are half a dozen in mid-stage trials and a few preclinical assets that might be ahead of '451. Stifel analysts suggest that that the approved drugs for this setting “have clear deficiencies”, but add that the EGFR exon 20 non-small cell lung cancer market is worth less than $500m annually. Leerink analysts were vastly more optimistic, forecasting peak sales of $600m in the exon 20 NSCLC niche and an NPV of $1bn, if the drug makes it all the way to market. There might be an advantage for ’451 in that it is said to be brain-penetrant – none of the approved or clinical-stage projects are known to have demonstrated meaningful CNS responses. But for Blueprint to get more than a small fraction of a tiny market LNG-451 needs to show remarkable benefits over those already available, when it does eventually yield clinical data.

Targeting folate receptor α seemed to be a dead end until developers threw antibody-drug conjugates at the problem, and a clinical win from Immunogen with mirvetuximab today could make the company first to market here. The pivotal Soraya trial, in FRα-high platinum-resistant ovarian cancer, met its primary endpoint, easily surpassing a minimum threshold (12% on the lower bound of the confidence interval). Five complete responses were seen, impressive considering that patients had received three prior lines of therapy, including Avastin. Median duration of response needed to reach six months for this result to be considered clinically meaningful, and that was almost achieved; Immunogen believes that with longer follow up mDOR might hit seven months. A 7% discontinuation rate due to adverse events is also encouraging, given the known toxicities of ADCs. Immunogen shares jumped 25% in early trade on hopes for accelerated approval next year, though the FDA might choose to wait for a second-line trial, Mirasol, to read out in the third quarter of 2022. Immunogen insists that combination strategies could unlock bigger potential for mirvetuximab and this mechanism, which is presumably what Bristol Myers Squibb was also thinking when it paid $650m for a similar asset from Eisai. 

One group of medtechs were largely resistant to Friday’s bloodbath on the markets: Covid-19 test developers. Several have been quick to clarify that their tests can accurately detect the new Omicron variant despite its many mutations, with Qiagen stating that all of its PCR tests for the virus had been assessed successfully against the variant using public genetic databases. Thermo Fisher went further, pointing out that its TaqPath PCR assays could distinguish Omicron infections from those caused by Delta, thanks to the so-called “S gene drop out”. The Alpha and Omicron variants have this genetic quirk, but Delta does not, and since Delta is now so prevalent any drop out samples seen recently are likely from patients with Omicron. Currently this has to be confirmed with full sequencing of the viral genome, but Thermo Fisher is also working on specific genotyping assays for Omicron. And on Friday, Eurofins launched a new test that can differentiate Omicron from Delta. Called GSD NovaType Select P681H, this assay can be used as a large-scale screening test for PCR-positive samples. Eurofins also sells tests that can distinguish Omicron from other variants of concern, and its US listing closed up 13% on Friday.

Investors were unconvinced by yesterday’s apparent mid-stage success with Ionis and Pfizer’s cholesterol-lowering project vupanorsen. On the face of it the anti-ANGPTL3 antisense did what it needed to do in the dose-ranging Translate Timi 70 trial, statistically lowering non-HDL cholesterol at all doses tested versus placebo at week 24. However, Pfizer’s commitment to the asset is far from clear: the big pharma left Ionis to report the results, and also seemed lukewarm about further development, only saying it was reviewing the findings before determining next steps. In another potential red flag, the study found liver enzyme elevations, primarily at the highest doses tested, as well as increases in hepatic fat fraction at “certain doses”. Ionis said there were no Hy’s law cases. More information is needed, but there must now be fears that the group might not be able to find a therapeutic window for vupanorsen; Ionis’s stock sank 2% yesterday and another 2% after hours. The liver findings could also throw doubt on ANGPTL3 as a target. However, the pivotal trial of Regeneron’s Evkeeza in homozygous familial hypercholesterolaemia was not marked by liver enzyme worries, something that could provide solace to other developers of anti-ANGPTL3 projects, though of course Evkeeza is a MAb, unlike the other projects in this space.