Snippet roundup: new CAR-Ts for old, and an unusual win for Alkermes

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

This week, April 16-20, 2018, we had thoughts on the following: Kymriah looks destined to disappoint; after consumer sale focus turns to German Merck’s pipeline; Novocure to file in mesothelioma on phase II data; Rigel wins best-case label for Tavalisse; AACR – Poseida tries to stand out from the crowd; Blueprint makes good start in RET competition; Alkermes stares down the FDA.

These snippets were previously published daily via twitter.

Kymriah looks destined to disappoint

April 19, 2018

Novartis has given the first clues about how its CAR-T therapy Kymriah might fare commercially – and the signs are not good. The company reported Kymriah sales of just $12m in the first quarter, leaving it with a huge mountain to climb if revenues are to reach the $156m forecast this year by EvaluatePharma sellside consensus. Still, the company was upbeat on today’s conference call, with its oncology chief, Liz Barrett, saying that early sales had been in line with expectations and that the group was expecting a “continuous improvement quarter-on-quarter, but it will take time for these centres to get up and running and used to using this new therapy”. This is clearly now the limiting factor, since reimbursement is going “very smoothly” and Novartis noted that the majority of lives were now covered by payers. Kymriah still has a shot in the bigger indication of diffuse large B-cell lymphoma (DLBCL), and a decision here is expected by early May.

After consumer sale focus turns to German Merck’s pipeline

April 19, 2018

The conglomerate that is Merck KGaA has become more focused, in healthcare at least, with the sale of its consumer unit to Procter & Gamble for €3.4bn ($4.2bn). The division generated sales of €911m last year, and analyst Wimal Kapadia at Bernstein liked the sale price. He said Merck had achieved a valuation equivalent to 10% of its market cap – which stands at €35bn – for only a 4% hit to earnings. Merck pledged to use the cash to pay back debt and strengthen all of its businesses, though it ruled out acquisitions of more than €500m until the end of 2018. It also said that despite the disposal it would be able to keep sales in its healthcare unit stable until at least 2022 – a surprising claim considering the approaching loss of exclusivity for several of its biggest sellers, including Rebif and Erbitux. The company’s pipeline becomes a focus, therefore, and data on its anti-PD-L1 antibody avelumab and c-Met kinase inhibitor tepotinib due later this year will be keenly awaited.

Novocure to file in mesothelioma on phase II data

April 19, 2018

US approval of Novocure’s electric field-based technology for mesothelioma is odds-on, analysts believe, after the company’s statement that the device had scored in a phase II pilot trial. Novocure plans to seek approval via the FDA’s Humanitarian Device exemption pathway, intended for products for rare diseases, based on these phase II results. The Stellar trial tested Novocure’s Optune system in combination with Lilly’s Alimta and cisplatin or carboplatin in 82 patients with pleural mesothelioma, using data from the 2003 phase III FDA registration trial of Alimta as a historical control. While the company has not disclosed detailed data it says the trial hit on all efficacy endpoints – the primary measure is one-year overall survival, with secondaries including PFS and response rate. In Alimta’s approval trial 50% of patients treated with Alimta plus cisplatin were alive at one year, so this is the figure Optune must have beaten. Analysts from Wells Fargo say there is a “high likelihood” of the HDE being granted, and with a review period of 75 days Optune could receive a mesothelioma indication by autumn, providing a sales boost of around $50m in 2019.

Rigel wins best-case label for Tavalisse

April 18, 2018

A decade of development spending finally paid off for Rigel with US approval of Tavalisse – this time for real – to treat chronic immune thrombocytopenia. And in an encouraging development the FDA granted a broad label that will allow the Syk inhibitor to challenge existing treatments. If front-line corticosteroids fail patients with this low platelet condition can be treated with thrombopoietin receptor agonists – Amgen’s Nplate and Novartis’s Promacta – and there was a risk that the FDA might dictate that these drugs be tried before Tavalisse. That has not materialised, giving Rigel the opportunity to push for early use of its drug. Of course the helping hand of a larger partner would be an enormous benefit, and Rigel has said it hopes to deliver a deal in 2019; a best-case scenario label should help. Still, efforts to broaden Tavalisse’s uses took a knock earlier this year with a failure in IgA nephropathy, while the drug’s potential in another rare condition, autoimmune haemolytic anaemia, remains to be confirmed. The identity of any partner and size of any deal will help shed light on what industry makes of the opportunity for Tavalisse; among the ever-optimistic sellside, some peak sales estimates sit at over $1bn. 

AACR – Poseida tries to stand out from the crowd

April 18, 2018

To have a shot at success in the crowded CAR-T world you have to do things better and differently, and Poseida Therapeutics, partnered with Johnson & Johnson, used the AACR meeting to whet investors’ appetites. While its poster was intended only to detail the design of its first phase I trial, with the autologous project P-BCMA-101, it unveiled preliminary data on the first three treated multiple myeloma subjects: one partial response and two lesion reductions, and no evidence of cytokine storm. What is different about Poseida? For transduction it uses not a viral vector but a Piggybac transposon, similar to the Sleeping Beauty system used by Ziopharm; its CARs’ binding domains are artificial Centyrin scaffolds, rather than being antibody-derived; it uses an undisclosed safety switch built into the CAR construct; and it positively selects for stem cell memory T cells that it claims give a 96%-pure, long-lived product. Poseida will ultimately be compared against other BCMA players like Bluebird, Novartis and Nanjing Legend, but the best might be yet to come: an allogeneic construct using Cas-Clover, a derivative of Crispr-Cas9, to knock out alloreactive proteins, is still in preclinical trials.

Blueprint makes good start in Ret competition

April 16, 2018

While some are setting up the competition between Loxo Oncology’s LOXO-292 and Blueprint’s BLU-667 as one of oncology’s new showdowns, for those with Ret-altered cancers any progress would be a win. And the latest phase I data from Blueprint at AACR should provide some hope. In the Arrow trial, which looked at 40 patients with a mixture of medullary thyroid cancer and non-small cell lung cancer, those with Ret mutations showed a 45% reduction in tumour size. Until now, those with Ret-altered cancers have had to use multikinase inhibitors such as Cabometyx or Caprelsa, which while hitting Ret are often associated with severe off-target toxicity. Encouragingly for Blueprint, there were no serious adverse events with BLU-667, with the most common one being mild constipation. Loxo is due to unveil its phase I data at Asco in June, and the results will be even more closely watched after the Blueprint data, with a focus on whether LOXO-292 has better selectivity to Ret. Sales estimates for both assets show that analysts believe that they will share this niche market evenly.

Alkermes stares down the FDA

April 16, 2018

For a moment there the US FDA almost looked tough. The agency has backtracked on its decision two weeks ago to refuse to accept Alkermes’s NDA for its antidepressant ALKS 5461, with the acceptance causing the company’s shares to open up 7%. Interestingly, no new data have been submitted; Alkermes makes it sound as if it simply sat down with FDA representatives and calmly explained to them that they were wrong. On a conference call today management refused to say exactly where the misunderstanding had been, instead stating that a huge amount of data were submitted and that “it took a while to get [the FDA’s] lens focused”. The PDUFA date is January 31, 2019, putting the project right back on track; a panel meeting is likely to be scheduled towards the end of this year. The question now is whether approval will actually be granted: with only one of its three pivotal trials posting positive data – and then with only one if its two doses – this has to be doubtful. Still, if the FDA refuses to approve the ALKS 5461, presumably Alkermes can have another meeting and persuade the agency to change its mind again.

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