Snippet Roundup: PI3Ks not dead, but PD(L)-1 multiple myeloma hopes falter

Welcome to your weekly roundup of EP Vantage’s snippets – short takes on smaller news items.

This week, September 4 to 8, 2017, we had thoughts on the following: Asthma data clear Pathway for Astra’s tezepelumab; Keytruda’s multiple myeloma fallout has Roche in the firing line; Duvelisib success shows PI3Ks are not dead; Avadel splashes out on newly approved night-time urination product; Teleflex moves on second substantial tuck-in; Indivior shareholders get withdrawal symptoms after patent ruling; The AML train keeps rolling with Mylotarg’s re-approval. 

These snippets were previously published daily via twitter.

Asthma data clear Pathway for Astra’s tezepelumab

September 7, 2017

Positive results from the phase IIb Pathway study of Astrazeneca’s asthma candidate tezepelumab give it a nice problem to have: a choice between prioritising that project or benralizumab, which is awaiting an approval decision from the FDA. Tezepelumab, a first-in-class anti-thymic stromal lymphopoietin (TSLP) MAb, has the advantage of apparent efficacy across all patients regardless of eosinophil levels, but Astra will only see a share of the profits from the Amgen-partnered asset. Meanwhile, Astra has full rights outside Japan for benralizumab, an anti-IL-5 antibody, but it is going for a smaller share of the market, patients with eosinophilic asthma. The Pathway study found a reduction in annual asthma exacerbations of 61-71% with three doses of tezepelumab, all significant versus placebo. This puts the results on a par with those seen in phase IIb with Sanofi and Regeneron’s anti-IL-4 & IL-13 MAb Dupixent, which has also shown activity regardless of eosinophil levels. Pathway might qualify as a registrational study for tezepelumab, Leerink analysts speculated. However, while safety in the study looked good, there are still question marks here, with an NEJM editorial raising concerns about targeting upstream cytokines through the inhibition of TSLP, including potential infections.

Keytruda’s multiple myeloma fallout has Roche in the firing line

September 7, 2017

With the fallout from the suspension of Keytruda’s programme in multiple myeloma spreading to Opdivo and Imfinzi, Roche’s Tecentriq looks next in line to have its clinical study in this setting halted. After Merck & Co paused enrolment into multiple myeloma trials of Keytruda in June the US FDA imposed a clinical hold, citing an increase in deaths in active treatment arms. This was followed this week by similar regulatory action on multiple myeloma trials of Opdivo and Imfinzi, with Bristol-Myers Squibb and Astrazeneca, whose haematological immuno-oncology programme is partnered with Celgene, putting the blame squarely on readacross from Keytruda. Interestingly, the FDA has also halted two non-myeloma studies of Imzinfi: MEDI4736-NHL-001 and MEDI4736-DLBCL-001 in lymphoma, both of which also include the multiple myeloma drug Revlimid. The only study of an anti-PD-(L)1 agent still ongoing in this malignancy seems to be that of Tecentriq, and no doubt Roche is keeping a close eye on FDA correspondence. The moves underline the view that immuno-oncology looks highly unlikely to make inroads into multiple myeloma.

Duvelisib success shows PI3Ks are not dead

September 6, 2017

The reports of PI3K inhibitors’ demise may have been premature. Verastem provided the best news this space has seen in some time when it reported positive data from the Duo trial of duvelisib today. The dual inhibitor of PI3K-delta and gamma was pitted against Arzerra in relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma. The Verastem agent showed a statistically significant improvement in progression free survival of 13.3 months to Arzerra’s 9.9 months, a statistically significant reduction of 48% in the risk of death or progression. The trial’s results will trigger the first payments to Infinity Pharmaceuticals, a $6m milestone, part of a $28m deal in which Verastem paid no up front fee to in-license the asset. This should not be a problem for Verastem, which saw its shares shoot up 29% in pre-market trading. Verastem executives said they will be discussing the trial results with US FDA officials with a goal of submitting a new drug application in the first half of 2018. The group also announced it will extend the clinical programme to include peripheral T-cell lymphoma in addition to CLL and non-Hodgkin lymphoma. Duvelisib had previously been out-licensed to Abbvie, which abandoned the project after disappointing results in the Dynamo study in non-Hodgkin lymphoma.

Avadel splashes out on newly approved night-time urination product

September 6, 2017

Avadel has deployed a substantial portion of its cash pile to buy Noctiva, a recently FDA approved product to treat nocturia, or frequent night-time urination. The cash-rich speciality pharma company, which was forged from Flamel at the beginning of the year, will pay Serenity Pharmaceuticals $50m up front for North American rights, $20m on full scale commercial launch, plus sales milestones and royalties. Avadel can afford this – the profitable company ended June with $173m on the balance sheet and no debt and felt sufficiently flush to spend $25m on share buy backs earlier this year – but it now needs to show that the product can sell. Although the company boasts that Noctiva is the first FDA approved product to specifically treat nocturia due to nocturnal polyuria, the active ingredient is desmopressin, a widely available generic anti-diuretic that is already used to treat the condition. Admittedly, Avadel intends to build the company on products just like this and the move fits with its stated strategy, but the chunky up front means that the pressure is on.

Teleflex moves on second substantial tuck-in

September 5, 2017

Teleflex wasted little time moving in on a second substantial acquisition, only a couple of months after closing the $1bn takeover of Vascular Solutions. This time however it is bolstering its urology business, with the purchase of California company Neotract for $750m up-front. The private device developer’s main asset is called UroLift System, a minimally invasive technology for treating lower urinary tract symptoms due to benign prostatic hyperplasia. NeoTract’s revenues are expected to hit $115m-$120m this year and growth of at least 40% is forecast for 2018; should certain sales targets be hit by 2020, Teleflex could pay out a further $375m in milestones. A next generation system is due to launch in late 2018. Teleflex had to rein in sales growth forecasts almost a year ago, blaming several geographical issues, but investors appear to have forgotten their concerns for now – shares in the Pennsylvania company have advanced 30% this year. While debt remains cheap acquisitions to bolster the top line and which very quickly add to earnings will always help – and Teleflex is giving no indication that its deal-making days are over.

Indivior shareholders get withdrawal symptoms after patent ruling

September 4, 2017

A US court decision opening the door to generics to its lead product proved to be huge body blow for Indivior wiping 35% of the value of the UK company on Friday. Indian generic company Dr Reddy’s can now make its own version of Suboxone Film, Indivior’s opioid addiction treatment. Last year Suboxone Film racked up $933m in sales for Indivior, accounting for more than 80% of total turnover, explaining the investor reaction. Dr Reddy’s, however, still needs to secure FDA approval for its product, which received a complete response letter in July. And Indivior is planning on appealing the ruling, meaning that if Dr Reddy’s launches following an expected approval in mid-2018 it would be launching at risk, something analysts expect. On a positive note for Indivior, a separate ruling upheld a previous decision knocking out potential competition from Watson and Par, judging that the two groups infringed another one of Indivior’s patents. This means Suboxone Film will at least only have one, and not multiple competitors next year. Indivior could also mitigate some of the damage from Dr Reddy’s with its own authorised generic. But real salvation will come in the form of RBP-6000 its follow-on once monthly injectable opioid addiction treatment. The ongoing opioid crisis in the US could mean sales of RBP-6000 hit their 2022 $872m forecasts.

The AML train keeps rolling with Mylotarg’s re-approval

September 4, 2017

Mylotarg is back. The industry’s first approved antibody drug conjugate (ADC) has been resurrected with an approval in acute myeloid leukaemia, following its 2010 withdrawal after the failure of confirmatory trials and safety concerns. But Pfizer is relaunching the drug into a vastly reshaped market. For one, ADCs have joined the mainstream of oncology, with Adcetris and Kadcyla having reached the market and generating healthy sales, and numerous others are nearing crucial data. For another, significant progress has been made in acute myeloid leukaemia (AML), albeit with distinctly different populations. Novartis’s Rydapt, Celgene’s Idhifa, Jazz’s Vyxeos and now Mylotarg have been approved since the end of April, and all treat different types of disease – FLT3, IDH2, high risk secondary and CD33-positive disease, respectively. Other new agents that could figure prominently in the disease include Abbvie and Roche’s Venclexta and Daiichi Sankyo’s quizartinib. Analysts have not prepared forecasts for Mylotarg. In 2009, its last full year on the market, it achieved $83m in sales for Pfizer and originator Wyeth.

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