Snippets

Vantage Snippets are short summaries of breaking news stories.

Novocure eyes a much bigger market

In February Novocure admitted that data from some of the clinical trials of its electric field-based cancer device would emerge later than expected. Today it seems the opposite might occur: the pivotal Lunar trial, assessing the Optune Lua technology in stage 4 platinum-resistant non-small cell lung cancer, looks as if it will be stopped early for efficacy. The study is comparing Optune Lua plus checkpoint inhibitors or docetaxel with the same drug regimen alone. An independent data monitoring committee has told Novocure that that it is “likely unnecessary and perhaps even unethical” for patients to be randomised into Lunar’s control arm. Neither is there a need to enrol the current target of 534 patients with 18 months’ follow-up; the DMC said around 276 patients, with a year’s follow-up, ought to provide sufficient power for Lunar’s endpoints. 210 had been enrolled by February, so final data could come next year, a year earlier than expected. Optune Lua is approved for mesothelioma, but NSCLC is a vastly larger market. Novocure’s share price rose 46% to an all-time high of $193 in early trade, giving the group a market cap of $21.5bn.

Regeneron moves ahead in Covid-19 prevention

Regeneron now has the edge in the race to produce antibodies to reduce the risk of Covid-19. The company today reported full results from a pivotal trial showing an 81% reduction in the risk of symptomatic Covid-19 in 1,505 subjects living with infected individuals. Additionally, triallists receiving Regen-Cov2 (casirivimab plus imdevimab) appeared to get better faster, recovering in one week compared with three for placebo. Regen-Cov already has emergency use authorisation for mild to moderate Covid-19, and these results – an update from a previous positive interim analysis that found 100% reduction in symptomatic Covid-19 – open the way for EUA in prevention. With vaccine programmes under way in many western countries Regeneron is unsurprisingly pitching Regen-Cov2 as complementary, arguing that where vaccination levels are low and individuals are at high risk of infection, for example in settings like nursing homes, there is space for the therapy. Unlike Lilly's rival antibody bamlanivimab, which is intravenous, Regen-Cov2 is injected subcutaneously, potentially widening its use. The US government has bought 1.25 million doses of Regen-Cov2, but it is unclear who will pay beyond this current epidemic, leaving pricing as well as increased vaccine rollout as potential barriers to future uptake.

AACR 2021 – Pieris might have to bet on combinations

Pieris’s lead Her2-targeting asset, PRS-343, has shown additional signs of monotherapy efficacy, though the data, revealed at AACR over the weekend, do not suggest a competitive profile. The molecule, an anti-Her2 x 4-1BB bispecific now known as cinrebafusp alfa, had spent half of 2020 on partial clinical hold, and its phase 1 study previously yielded a 13% remission rate in Her2-positive tumours. With 42 evaluable subjects the ORR reported at AACR is now 12%, with all five remissions, including one complete, occurring on 8mg/kg every two weeks. This includes one additional response in an unknown cancer, and the deepening of an earlier partial response into a complete remission. But this is where the good news ended: three of the responding subjects, including the one with a CR, have relapsed. Pieris highlighted preliminary evidence of PRS-343’s activity in poorly immunogenic and low-Her2 expressing tumours, but it seems likely that the project’s best chances to compete against the likes of Enhertu will be as part of combinations. A separate phase 1 trial with Tecentriq is ongoing, while a phase 2 test combining PRS-343 with Lilly’s Cyramza or Seagen’s Tukysa is to begin in the summer.

Source: Dr Sarina Piha-Paul & AACR.

Hologic goes big on infections

Hologic’s fourth acquisition this year, that of the Finnish testing group Mobidiag, is its largest since it purchased Cynosure in 2017, and the company will hope that it is a much better bet than that disastrous earlier deal. Hologic, a specialist in women’s health, bought Mobidiag for $714m in cash and took on the private company’s net debt of $81m. Mobidiag makes PCR-based tests for gastrointestinal and respiratory infections, antimicrobial resistance and healthcare-associated infections. Naturally it has Covid-19 tests, but these are only available in Europe so far. Hologic has US emergency authorisation for its own Covid-19 assays, and the vast sales these have accrued over the past year – in the three months up to December 26 its diagnostics revenues were up 450% year on year – have fuelled this year’s deal making. Leerink puts the annual growth rate of the acute care testing market at around 20%, and says Mobidiag can grow at closer to 3% annually once it is in Hologic’s hands. Still, Mobidiag’s sales only came in at $42m last year, so this is a low base from which to grow.

Hologic's M&A, 2017-21
Date Deal type Target Value ($m) Focus
Apr 8, 2021 Acquisition Mobidiag 795 In vitro diagnostics
Mar 1, 2021 Acquisition Diagenode Diagnostics 159 In vitro diagnostics
Feb 22, 2021 Acquisition Biotheranostics 230 In vitro diagnostics
Jan 4, 2021 Acquisition Somatex Medical Technologies 64 General & plastic surgery; radiology
Aug 25, 2020 Acquisition Acessa Health - General & plastic surgery
Aug 1, 2019 Minority stake Supersonic Imagine 18 Diagnostic imaging
Jun 20, 2019 Option Supersonic Imagine 85 Diagnostic imaging
Oct 1, 2018 Acquisition Focal Therapeutics 125 General & plastic surgery; radiology
Jul 31, 2018 Acquisition Faxitron Bioptics 85 Diagnostic imaging
Mar 22, 2017 Acquisition Cynosure 1,650 General & plastic surgery; general hospital & healthcare supply
Source: Evaluate Medtech & company releases.

Keytruda’s latest kidney cancer win: adjuvant use

If February’s positive readout of the Clear study gave Merck & Co’s Keytruda an important lead over its rivals in front-line kidney cancer, today’s apparent win in Keynote-564 could stretch the advantage further still. Keynote-564 was the first of several pivotal immunotherapy studies to read out in this cancer’s even earlier, adjuvant setting, a market currently untapped by anti-PD-(L)1 drugs. Adjuvant and neoadjuvant settings are becoming key battlegrounds for checkpoint-blocking drugs, but kidney cancer is somewhat under the radar. Nevertheless, all the big players are running phase 3 trials. Merck has said nothing about the magnitude of Keytruda’s disease-free survival win in Keynote-564, except that this is statistically and clinically significant; whether this endpoint is sufficient for approval rather than the gold standard of overall survival is up to regulators. However, bulls will note that DFS is a more robust measure than pathological complete response, the endpoint on which Merck tripped up when trying to extend Keytruda’s label to perioperative triple-negative breast cancer; that setting will require the company to wait until the Keynote-522 trial reads out for event-free survival.

Pivotal trials of anti-PD-(L)1 drugs in adjuvant renal cell carcinoma
Study Drug(s) Primary endpoint(s) Result
Keynote-564 Keytruda vs placebo DFS Said to be statistically significant & clinically meaningful for DFS
Immotion-010 Tecentriq vs placebo DFS Primary completion Jan 2022
Checkmate-914 Opdivo +/- Yervoy vs placebo DFS Primary completion Apr 2023
Rampart Imfinzi +/- tremelimumab vs placebo DFS & OS Primary completion Jul 2024
Source: Mizuho & clinicaltrials.gov.

Hopes fade for novel anaemia pills, but could Glaxo yet prevail?

Imagine the scenario: Glaxosmithkline, the wild card in the novel anaemia pill race, swoops in with a late but clean pivotal programme with daprodustat, serving up a HIF-PH inhibitor that regulators can approve with confidence. The mechanism finally delivers on its promise in anaemia with chronic kidney disease, with a safe and convenient oral option to replace EPO infusions that risk cardiotoxicity. This seems highly unlikely, unfortunately, given the failure of both Fibrogen and Akebia to generate convincing safety packages with their respective contenders, roxadustat and vadadustat. The former was rocked by a barely believable data error this week, and the latter failed a key cardiac safety test. Regulators therefore have very good reason to be wary of the class. Glaxo’s daprodustat holds the potential to swing opinion, but which way depends on the readout of two major pivotal trials, due in the second half. Consensus forecasts suggest that hopes are low: numbers have come down for vadadustat and daprodustat in the last 12 months, according to Evaluate Pharma, and roxadustat's are likely to follow soon. The HIF-PH inhibitors’ fate should be known by year end; it is hard to picture a resurrection.

The convoluted world of the HIF-PH inhibitors: destined to be big only in Japan? 
Company Rights and regions Status 
Roxadustat
Astrazeneca US, China and others Filed in the US; adcom Jul 15
Fibrogen Certain US and China rights Filed in the US; adcom Jul 15
Astellas  Japan, Europe and others Filed in Europe, decision due by mid-year; marketed in Japan (as Evrenzo)
Vadadustat
Akebia  US co-promote/profit share, royalties elsewhere Awaiting US FDA acceptance of NDA; marketed in Japan (sold by Mitsubishi as Vafseo)
Vifor Pharma  US profit share in dialysis population -
Otsuka  US co-promote, Europe, China and other regions Europe fillings due this year
Daprodustat
Glaxosmithkline WW ex Japan Ascend-D and Ascend-ND readouts due H2 2021
Kyowa Kirin Japan Marketed in Japan (as Duvroq)
Source: Evaluate Pharma. 

Pear hopes new deals will bear fruit

The deals announced by Pear Therapeutics yesterday, with Empatica, Etectrx and Keywise, represent the convergence of several aspects of digital health. They also represent an attempt by the company to diversify away from its core technology of prescription apps, which have yielded lacklustre data and been deserted by Pear’s development partners, Novartis and its subsidiary Sandoz. Certainly the company is not abandoning its apps, several of which are on the market in the US – in one case, temporarily – as therapies for addiction and neurological conditions. Instead it is working to incorporate other companies’ technologies, including wearables, sensors and keystroke trackers, to make its products more useful. The new deals add to the licence Pear signed last year with Winterlight Labs, under which it gained Winterlight’s voice analysis software which the company claims can assess a patient’s cognitive health. No financial details were released for any of the deals listed below. Pear’s embracing of remote physiological sensing is not a bad idea considering its recent run of bad news, and it will be interesting to see whether other prescription app makers like Orexo and Click Therapeutics pursue a similar approach. 

Pear Therapeutics' digital partnerships
Partner Technology Purpose
Empatica A smartwatch that can track heart rate, fine locomotor behaviours and skin temperature and conductance To evaluate withdrawal symptoms in patients with addictions to opioids, alcohol and other substances
Etectrx  ID-Cap digital pill, an ingestion marker To enhance medication adherence 
Keywise Artificial intelligence-enabled keystroke detection algorithm To track and produce mental health metrics in indications including depression, bipolar disorder, schizophrenia, substance use disorder, opioid use disorder, insomnia and pain
Winterlight Labs* Machine learning-based voice analysis software To develop digital biomarkers for diseases including Alzheimer’s, depression, insomnia, schizophrenia and opioid use and substance use disorders
*Winterlight agreement dates from 2020, all others announced April 6, 2021. Source: company release.

Back to the drawing board for Molecular Templates

Takeda’s decision to give up on the Molecular Templates-originated TAK-169 makes sense given the competitive nature of the molecule’s target, CD38, but it will raise doubts over the junior partner’s approach. This technology revolves around so-called engineered toxin bodies (ETBs), which comprise toxic payloads fused to antibody-derived binding domains, resulting in smaller and possibly more tumour penetrative constructs than typical antibody-drug conjugates. This seems an attractive proposition, but unfortunately ETBs have yet to deliver a knockout blow clinically, and Takeda’s move follows months of stalling: TAK-169 was to have delivered efficacy data last year, but its trial has only enrolled four subjects. Molecular Templates stock fell 24% yesterday as the group also switched its focus to second-generation ETBs; MT-3724, a first-gen ETB that had been put on clinical hold after a treatment-related death, has now been discontinued. It will not help sentiment that TAK-169 is a second-generation construct, and that one of the four subjects treated with it experienced dose-limiting, grade 2 myocarditis. The patient had had multiple pre-existing cardiac risk factors, so this could well be unrelated to TAK-169, but the overwhelming question for investors is whether the ETB approach is quite ready for prime time.

Molecular Templates' R&D pipeline
Project Target ETB type Features Status
MT-3724 CD20 1st gen Wild-type toxin + targeting ScFv domain Discontinued after ph2 was put on clinical hold
MT-5111 Her2 2nd gen Engineered toxin + targeting ScFv domain Ph2 starting May 2021
TAK-169 CD38 2nd gen Engineered toxin + targeting ScFv domain Ph1; Takeda handed back rights
MT-6402 PD-L1 3rd gen Engineered toxin + targeting ScFv domain + antigen seeding Ph1 starting May 2021
TBD CTLA-4 2nd gen* Engineered toxin + targeting ScFv domain 1 of 5 constructs to start clinical trials in 2021
TBD CS1 2nd gen* Engineered toxin + targeting ScFv domain Preclinical
TBD CD45 2nd gen* Engineered toxin + targeting ScFv domain Preclinical
TBD CD20 2nd or 3rd gen TBD Preclinical
Source: company filings. Note: *according to preclinical posters. ETB=engineered toxin body.

US FDA approval tracker: March

Fibrogen and Astrazeneca had been gearing up for an approval decision on their chronic kidney disease project roxadustat last month, but a surprise advisory panel meeting is now in the works, at a date yet to be determined. Experts will play close attention to cardiac safety issues with the oral HIF-PH inhibitor. Akebia, which recently filed vadadustat, a similarly acting project with its own toxicity problems, will be watching the adcom with interest. Elsewhere, Keytruda got knocked back in neoadjuvant/adjuvant triple-negative breast cancer after a negative vote from an earlier panel meeting. Merck & Co will likely have to wait for data on event-free survival from the Keynote-522 study to get another shot here; these are due in the third quarter. Merck also voluntarily withdrew Keytruda's use in small-cell lung cancer. The anti-PD-1 antibody, alongside Roche's Tecentriq and Bristol's Opdivo, will be the subject of a panel towards the end of April looking at accelerated approvals for six indications in which confirmatory studies have failed (Go or no go? The FDA plays hardball, March 30, 2021).

Notable first-time US approval decisions in March
Project Company 2026e sales by indication ($m) Outcome
Evrenzo (roxadustat) Astrazeneca/Fibrogen/
Astellas
2,656 Adcom planned, no date disclosed
Abecma (ide-cel) Bristol Myers Squibb/
Bluebird
1,198 Approved
Mirabegron oral suspension Astellas 579* Approved
Dostarlimab Glaxosmithkline 537 No decision yet
DaxibotulinumtoxinA Revance 356 No decision yet
Rolontis Spectrum 344 Pre-approval inspection scheduled for May
Zegalogue (Dasiglucagon HypoPal Rescue Pen) Zealand Pharma 268 Approved
Fotivda Aveo 155 Approved (~3 weeks early)
Trevyent United Therapeutics 41 Company discontinued development after receiving FDA comments; CRL in Apr 2020
Azstarys (KP145) Kempharm/
Aquestive
- Approved
Ponvory (ponesimod) J&J/Idorsia - Approved
Besremi (ropeginterferon alfa-2b) AOP/PharmaEssentia - CRL (manufacturing inspection delay)
*Includes sales for tablet version (Myrbetriq). Source: EvaluatePharma & company releases.

 

Advisory committee meetings in March
Project Company  2026e sales by indication ($m) Note
Tanezumab Lilly/Pfizer 179 Negative, Pdufa estimated in Apr
Source: EvaluatePharma & FDA adcom calendar.

 

Supplementary and other notable approval decisions in March
Product Company Indication (clinical trial) Outcome
Sarclisa Sanofi R/r multiple myeloma, combo with Kyprolis & dexamethasone Approved (~3mth early)
Yescarta Gilead R/r follicular lymphoma & marginal zone lymphoma after ≥2 systemics (Zuma-5) Approved
Arcalyst
(rilonacept)
Kiniksa Recurrent pericarditis (Rhapsody) Approved 
Exparel Pacira Postsurgical analgesia in children aged ≥6 (Play) Approved 
Myrbetriq
(mirabegron tablets)
Astellas Neurogenic detrusor overactivity in patients aged ≥3 (NCT02751931) Approved
Keytruda Merck & Co TNBC in combo with chemo as neoadjuvant, also single agent as adjuvant (Keynote-522) CRL (negative adcom in Feb)
Keytruda Merck & Co 1L oesophageal/gastroesophageal junction carcinoma (Keynote-590) Approved 
Xolair Roche/Novartis Self-administration option across all approved US indications No decision yet
Vazalore Plx Pharma Liquid-filled aspirin capsule (325mg and 81mg doses) Approved
Lorbrena Pfizer 1L Alk +ve NSCLC (Crown) Approved
Kimyrsa/
Orbactiv
Melinta Acute bacterial skin and skin structure infections, single one-hour infusion  Approved
Source: EvaluatePharma & company releases.
 
Voluntarily withdrawn accelerated approvals in March
Product Company Setting (failed confirmatory study)
Keytruda Merck & Co 3L SCLC (Keynote-604)
Tecentriq Roche 1L urothelial bladder cancer (Imvigor-211)
Source: company releases.

Health tech Spacs drift downwards

2021 has seen a startling rise in the number of deals between special-purpose acquisition companies and medical technology, digital health and diagnostics groups seeking a fast and easy way to go public. A flurry of these deals in February was followed this week by Somalogic reversing into CM Life Sciences II in a transaction worth $651m, including a $375m Pipe investment. Somalogic specialises in protein analysis, and plays in three industries: clinical diagnostics, with its SomaSignal assays for cardiovascular disease, diabetes and cancer; aiding drug development; and basic research. Its revenues in 2020 were just $55m, but the Spac deal will bring Somalogic’s pro forma enterprise value to $1.2bn. News of the deal pushed CM’s share price up 10%, but this is an outlier among the class of 2021 – most have seen their valuation fall since announcing deals. Indeed the shine is perhaps coming off Spacs, at least in the health tech space. VG Acquisition Corp, the blank-cheque company backed by Virgin, has lost nearly a quarter of its value since announcing its intent to buy 23andMe – a fall rendered all the steeper by the fact that its value had soared 31% on the day of the announcement

Health tech Spac deals in Q1 2021
Target Spac (main backer)  Focus Deal announced Share price since announcement
Somalogic  CM Life Sciences II (Casdin Capital and Corvex Management) Proteomics Mar 29 10%
Humacyte Alpha Healthcare Acquisition Corp (AHAC Sponsor) Bioengineered vascular grafts Feb 17 4%
Owlet Baby Care Sandbridge Acquisition Corp (Sandbridge Capital and Pimco) Digital health  Feb 16 (6%)
Sharecare Falcon Capital Acquisition Corp (Falcon Equity Investors) Telehealth Feb 12 (15%)
Sema4 CM Life Sciences (Casdin Capital and Corvex Management) Genomics Feb 10 (4%)
Nautilus Biotechnology Arya Sciences Acquisition Corp III (Perceptive Advisors) Proteomics Feb 8 23%
23andMe VG Acquisition Corp (Virgin Group) Genetic testing Feb 4 (24%)
Talkspace Hudson Executive Investment Corp (Hudson Executive Capital) Telehealth Jan 13 (14%)
Source: company announcements. 
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