Snippet roundup: Shire's Lialda goes generic and Novartis whets CAR-T appetites

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

This week, June 5 to 9, 2017, we had thoughts on the following: Novartis whets CAR-T appetites ahead of full data disclosure;  Shire not gutted by Lialda generic; Quarterly dosing works for Teva’s migraine drug; Interim data prompt Nanobiotix to quintuple size of head and neck trial; Lack of stroke effect does not stop Sentinel clearance; FDA backs valve-in-valve use of Edwards’ Sapien; Investors light up Earlens with $118m; Glaxo gains ground against Gilead. 

These snippets were previously published daily via twitter.

Novartis whets CAR-T appetites ahead of full data disclosure 

8 June, 2017

Top-line interim data from Novartis’s keenly awaited Juliet trial of CTL019 did not fail to impress, with the pharma giant unveiling very encouraging response rates from the CAR-T project in lymphoma yesterday. The indication could represent a much larger patient population for the therapy than paediatric ALL, in which Novartis is already seeking US approval; it was also revealed this week that an FDA Advisory Committee will review the ALL application on July 12. However much remains to be learned when the full results of the lymphoma trial are presented at the International Conference on Malignant Lymphoma in Lugano, Switzerland, on June 14. Deeper explanations for the difference between the enrolment rate and the infusion rate will be sought – of the 141 patients enrolled 43 discontinued before infusion, although in a press release Novartis sought to downplay any concerns about manufacturing by pointing out that only nine of these cases were down to the inability to make adequate doses of the CAR-T cells. And baseline patient comparisons will also be of interest, given that post-transplant patients are expected to have a much better prognosis. 51% of Juliet patients had received stem cell transplants, it emerged; this compares with 20% of patients in Kite Pharma’s Zuma-1 study and 57% in Juno’s Transcend trial. These full data will allow CTL019 to be held up to these rivals’ efforts more rigorously. 

Shire not gutted by Lialda generic

8 June, 2017

The FDA approval of Zydus Cadila’s generic version of Lialda is not the nightmare it once could have been for Shire – it is only the company’s twelfth-biggest product by net present value according to EvaluatePharma. But the entry of a generic this year, rather than in 2020 as expected, would still wipe 65% off Lialda’s value, giving the product an NPV of just $662m. Shire’s US stock fell 2% yesterday, while Cadila’s were up 9%, reflecting the fact that the approval has come faster than expected. However, a positive decision had been expected after the US Court of Appeals came down in its favour in May. Cadila has reportedly said it will launch the generic in July or August. Leerink analysts believe that the company will have 180-day exclusivity, which would stop the likes of Teva launching this year – and would also be good news for Shire. Luckily for Shire it has already moved on, helped by the acquisition of Baxalta, which developed three of its forecast top-five products in 2022. But losing Lialda’s exclusivity sooner rather than later will still be a blow to its profits.

Quarterly dosing works for Teva’s migraine drug

7 June, 2017

Teva already had positive results for fremanezumab in chronic migraine in the bag, so announcement that it also hit in episodic migraine is confirmation of the CGRP antibody’s effect. Monthly injections of fremanezumab resulted in a reduction of 3.7 migraine days per month compared with 2.2 for placebo, from a baseline of 9.1 per month, a statistically significant difference. A quarterly injection resulted in a reduction of 3.4 migraine days per month, also a statistically significant reduction. Quarterly dosing is one way Teva is hoping it will be able to differentiate itself from CGRP antibodies being developed by Amgen/Novartis, Eli Lilly, and Alder. Teva expects to submit its FDA application later this year, putting in close competition with Amgen and Lilly.

Interim data prompt Nanobiotix to quintuple size of head and neck trial

6 June, 2017

Last month data emerged suggesting that Nanobiotix’s radioenhancer nanoparticle therapy might be able to alter soft tissue sarcoma tumours to make them vulnerable to the patient’s immune system. Yesterday at the Asco meeting the French group presented data which seem to point to a similar effect in head and neck cancer (abstract 6080). Interim results from 11 evaluable patients from a European phase I/II trial assessing NBTXR3 in stage 3 or 4 head and neck cancer showed a 91% overall response rate. According to Bryan Garnier analysts, radiotherapy alone has an overall response rate below 40% in these late-stage patients. Complete response was seen in 78% of patients treated with a dose of 10% or less of baseline tumour volume. This response was seen between three and 10 months after the end of treatment, which the analysts say suggests that NBTXR3 might trigger a specific adaptive immune pattern. All patients treated at the 15% and 22% dose levels showed prolonged responses, with no relapses or metastasis, at a median follow-up of 12 months. Based on these data Nanobiotix has decided to amend the trial to add another 44 patients from both Europe and the US in an expansion cohort.

Lack of stroke effect does not stop Sentinel clearance

6 June, 2017

Claret Medical’s Sentinel embolic protection device has bagged FDA clearance, but the company’s battle is far from over. It will now have to convince clinicians to use a product that has not been proven to achieve its main goal – preventing stroke in patients undergoing transcatheter aortic valve replacement (TAVR). In Sentinel’s favour, it is the only device to get the go-ahead in the US for this use. And it does not appear to be dangerous: it met its safety endpoint in a pivotal trial, and has been cleared via the low-risk de novo 510(k) pathway. The decision was not entirely unexpected, after a panel endorsed Sentinel in February, but did not carry out a formal vote – not voting is customary with de novo applications. And in spite of the pivotal trial not hitting its primary efficacy endpoint of median new lesion volume, Claret has highlighted a 63% reduction in stroke in the first 72 hours after TAVR versus unprotected patients. The sieve-like device also caught debris in 99% of patients in the study. The company will have to hope this will be enough to persuade doctors as Sentinel is its only product.

FDA backs valve-in-valve use of Edwards’ Sapien

6 June, 2017

Edwards Lifesciences has entrenched its domination of the transcatheter aortic valve market with approval of its Sapien 3 valve for valve-in-valve procedures – the deploying of a new prosthetic valve within a first, failed one. And in a world-first, the approval covers valve-in-valve use in both the aortic and mitral positions, allowing Edwards to increase its lead over its main rival Medtronic. The approval specifically covers Sapien 3’s use in patients at high or greater risk of death or complications from open-heart surgery – it is already approved in the US as the initial prosthetic valve in patients at extreme, high and intermediate surgical risk. In trials, it appeared much safer than replacing the failed valve surgically: in both aortic and mitral valve-in-valve patients, the observed mortality rates were substantially lower than what would have been expected for repeat surgery. Edwards will conduct a post-approval surveillance study in these settings over the next five years.

Investors light up Earlens with $118m

6 June, 2017

Californian group Earlens has just raised $118m in debt and equity to fund commercialisation of its hearing aid, which uses light to transmit sound data in a process the company says allows better performance than traditional models. Earlens has obtained $73m from an offering of Series C preferred stock – a second close of a deal that brought it $51m last July – and $45m from a structured debt facility with healthcare investment company CRG. Investors in the series C offering include Medtronic and Australian hearing implant developer Cochlear, as well as eight investment groups and foundations, including CRG. The Earlens device was cleared by the FDA for use by adults with mild to severe sensorineural hearing impairment in October 2015, and is custom moulded to the patient’s eardrum via a non-surgical procedure. A photoreceptor faces out through the ear canal, and a probe connected to an audio processor placed behind the ear transmits sound data to the photoreceptor as pulses of non-visible light. The new funding will go towards scaling up manufacture of the device and expanding sales, as well as R&D on new or next-generation devices – but it is hard to see Earlens competing with the much larger hearing aid groups GN Store Nord, William Demant and Sonova.

Glaxo gains ground against Gilead

5 June, 2017

Glaxosmithkline has stolen a march on its HIV rival Gilead, using a priority review voucher to set up an FDA approval decision on its new doublet by the end of the year. Glaxo bought the voucher for $130m, which will be booked in its second-quarter results. The doublet, which combines Glaxo’s dolutegravir with Johnson & Johnson’s Edurant, could reach the market before Gilead’s triplet, bictegravir/F/TAF, which recently showed non-inferiority – but not superiority – to dolutegravir-containing regimens, including the marketed triplet Triumeq. Bictegravir/F/TAF also showed non-inferiority in two switching studies. Gilead plans to file its triplet in the second quarter, and could also use a priority review voucher. But it now looks to have been beaten by Glaxo, whose filing was based on data from the Sword 1 and 2 studies, presented at the CROI meeting in February. Both dolutegravir and bictegravir, next-generation integrase inhibitors – taking another drug to raise circulating levels – so have a lower risk of adverse events and drug-drug interactions. And a doublet could have an even lower side-effect burden. Nonetheless, while Glaxo is gaining market share from Gilead, the latter is still forecast to dominate the HIV market.

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