Welcome to your weekly roundup of EP Vantage’s snippets – short takes on smaller news items.
This week, April 24 to 28, 2017, we had thoughts on the following: Sanofi diabetes disappointment a prelude to Novo report;Is Tesaro planning a Zejula combo for TSR-042?; Medicines Co hopes to avoid inclisiran outcomes study; Second Otsuka deal solves Akebia’s cash problem; Amgen pullback signals CGRP caution; BMS deal injects life into Transgene’s TG4010; Xbiotech sinks as EU cools to symptom control case.
These snippets were previously published daily via twitter.
Sanofi diabetes disappointment a prelude to Novo report
April 28, 2017
Sanofi’s first-quarter earnings report was probably as much a warning for Novo Nordisk investors as it was a barometer for the French group’s performance. In the midst of an otherwise positive report as it beat earnings per share expectations, Sanofi disclosed a 7.7% shrinkage in its diabetes and cardiovascular business over first quarter 2016 sales. Lantus sales shrank 14% to $1.2bn, in-line with analyst forecasts, while Toujeo’s 78% growth to $192m came in 9% below expectations; strong performance from its consumer health business, vaccines and rare disease portfolio helped offset the performance of its long-acting insulins. Pricing pressure and formulary exclusions from US payers has been largely blamed for stumbles in the diabetes sector. Following the mixed diabetes outlook from Eli Lilly’s first-quarter report earlier this week, all eyes will turn to Novo Nordisk, which reports Wednesday, May 3. Sanofi investors responded to the otherwise positive quarter by pushing shares up 1% today.
Is Tesaro planning a Zejula combo for TSR-042?
April 28, 2017
Tesaro’s disclosure of a fast-to-market strategy for its early anti-PD-1 antibody TSR-042 poses the question of whether it will select this agent over a more advanced competitor – most likely Merck & Co’s Keytruda – in planned approval studies with its recently approved Parp inhibitor, Zejula. Last month, the US biotech said it would undertake phase III studies of Zejula in combination with an undisclosed anti-PD-1 in non-small cell lung, ovarian and triple-negative breast cancers in a major expansion of development activities that followed the drug’s US approval. The internal combo strategy may seem obvious for commercial reasons, but it is also risky when ’042’s PD-(L)1 competitors are approved or further ahead in these indications. Moreover, its PD-1 combination choice might affect the timing or value of a possible takeout offer – Tesaro being widely considered one of the most attractive M&A targets in the industry. In the meantime, Tesaro is focused on a pivotal trial of ’042 in recurrent endometrial cancer in the 20-25% of patients with microsatellite instability high phenotype. No competitor is yet targeting this patient group, though Keytruda is under FDA review for MSI-high solid tumours.
Medicines Co hopes to avoid inclisiran outcomes study
April 26, 2017
The Medicines Company’s suggestion that it will not need to carry out a cardiovascular outcomes trial for approval of its LDL-lowering project inclisiran got a mixed reception. Investors pushed the group’s stock up as much as 4% in early hours trading, but it opened down 2%, reflecting the fact that there are still reasons to be cautious. The company said that a 3,000-patient phase III trial will be enough to support an NDA, based on its end-of-phase II meeting with the FDA, but this will not be put to the test until a planned filing in late 2019. And there are also question marks over who will fund a supplemental 14,000-patient CVOT trial as the group has previously said it cannot afford to do this alone. Maybe Medicines Company is hoping the news will finally help it flush out a partner for inclisiran, which is injected subcutaneously every six months. But the conventional PCSK9 inhibitors, Amgen’s Repatha and Sanofi and Regeneron’s Praluent, already face questions over whether their cardiovascular benefit is worth the price tag. With inclisiran showing similar LDL-lowering effects in phase II, as well as raising safety worries, it might take more than this to convince the bigger players of its potential.
Second Otsuka deal solves Akebia’s cash problem
April 26, 2017
Any worries that Akebia was in danger of running out of cash before completing its large phase III kidney disease anaemia programme have been assuaged with a second deal with Otsuka. This gives the Japanese company rights in Europe, China and other territories on top of the fifty-fifty US profit share agreement signed in December – and takes its total up-front cash commitment to $473m, above Akebia’s current market cap of $364m. The company still lags behind Fibrogen in the hypoxia inducible factor prolyl hydroxylase (HIF-PH) inhibitor space, which goes some way to explaining the latter’s much larger market cap of nearly $2bn. But if the mechanism works – and with concerns about Akebia’s funding receding – the smaller group could be due an uplift. Indeed, Akebia’s stock climbed 33% in premarket trading this morning. The early signs for HIF-PH inhibitors are positive: Fibrogen announced in January that two Chinese phase III studies of its candidate roxadustat had met their primary endpoints, and various other phase III trials are due to report this year. Akebia, which also has Glaxosmithkline breathing down its neck, will have to wait until late 2018 or early 2019 for pivotal results with its project vadadustat. But at least now it has the resources to get there.
Amgen pullback signals CGRP caution
April 25, 2017
Amgen has backed away from the anti-CGRP migraine market with changes to its agreement with Novartis that will see the latter co-commercialising erenumab in the US and gaining Canadian rights. A look at the change in consensus forecasts shows that, of the four CGRP MAbs in phase III, erenumab has seen the biggest upgrades over the past nine months, suggesting that Amgen is taking a different view to the sellside. With the class having only a marginal benefit in migraine and the field looking crowded, perhaps Amgen does not have the stomach for another battle so soon after its scrap with Sanofi and Regeneron in the PCSK9 market. Novartis, meanwhile, will benefit from its existing sales force in neurology. Erenumab is still expected to be the first CGRP inhibitor to reach the market, with filing expected in the second quarter, which could give it an important advantage. However, Amgen’s decision hints that expectations for the field are overblown.
BMS deal injects life into Transgene’s TG4010
April 25, 2017
Transgene’s clinical collaboration to study its TG4010 cancer vaccine in combination with Bristol-Myers Squibb’s Opdivo and chemo in first line non-small cell lung cancer has injected some life back into an otherwise moribund programme. However, it is still yet some way from a registration plan. The planned phase II study will recruit NSCLC patients with low or undetectable PD-L1 expression, an underserved target group and one based on a post hoc analysis of data from its prior studies. However, the new study is single-arm and measures only overall response rate for the triple combination, so barring a highly unusual result, seems unlikely to support a future registration on its own. Furthermore, Bristol’s strategy in first-line NSCLC is heavily focused on the Opdivo/Yervoy dual checkpoint combo and its Checkmate-227 phase III study – which has a PD-L1 negative cohort – is due to read out results early next year. Transgene previously tested TG4010 in combination with chemo in the phase II/III Time study, but had to abandon the second pivotal stage for both funding and competitive reasons. The Time study nevertheless showed a PFS benefit in patients with normal levels of a biomarker called TrPAL, based on CD16, CD56 and CD69 positive lymphocytes.
Xbiotech sinks as EU cools to symptom control case
April 25, 2017
Xbiotech had hoped to persuade EU regulators that its colorectal cancer project Xilonix was approvable, but instead saw its stock hammered on Friday. This followed its presentation of data at an “oral explanation” meeting, which prompted the European Medicines Agency’s human medicines committee to issue a “negative trend” vote, meaning that Xilonix is unlikely to receive a positive opinion at the committee’s May meeting. Xbiotech was hoping to persuade the EU regulators that its significant effect on “symptom control” – defined as pain, fatigue, appetite and muscle mass – was sufficient for approval of Xilonix, which the company now calls Hutruo. The European regulators have challenged the statistical significance and clinical relevance of the individual endpoints in the symptom control analysis, and shares fell 40% to $10.23 on Friday, putting the company’s valuation at $359m.