Welcome to your weekly digest of approaching regulatory and clinical readouts. Following its drisapersen disappointment, BioMarin Pharmaceuticals is getting back to what it knows best: super-rare diseases. The company is expecting key readouts in Pompe's disease and CLN2 disorder in the next few months.
Argos Therapeutics is due to report phase III results with its dendritic cell immunotherapy AGS-003, or rocapuldencel-T, in renal cell carcinoma next year. However, there are reasons to be sceptical of its success, including the fact that it remains unpartnered and the track record of these types of treatments.
Pompe and circumstance
The expected December approval of BioMarin’s big hope, drisapersen, was thrown into doubt last month by a critical advisory committee (FDA parks BioMarin while Sarepta readies for its big day, November 25, 2015). So, although they are not set to be huge sellers, orphan disease candidates reveglucosidase alfa and cerliponase alfa could provide some much-needed Christmas cheer for the company.
The former drug is being trialled in late-onset Pompe's disease, the milder form of an inherited disorder that leads to progressive weakening of the muscles, including those that control breathing – respiratory failure is a common cause of death.
Reveglucosidase alfa is designed to replace the enzyme acid alpha-glucosidase (GAA) that is missing in patients with the disorder.
BioMarin should soon find out if the strategy holds merit: interim results from a phase II/III trial of the drug are expected by the end of 2015. Patients who have been switched to reveglucosidase from alglucosidase alfa will be assessed on a primary outcome of change from baseline in maximum inspiratory pressure at 24 weeks. Secondary endpoints include maximal expiratory pressure and the six-minute walk test.
The company has a second shot with cerliponase alfa in late-infantile CLN2 disorder, another genetic disease that decreases levels of an enzyme, in this case TPP1.
A phase I/II study of cerliponase alfa is expected to finish by the end of the year and report in Q1 2016. Efficacy is being measured using the CLN2 disease rating scale. If positive, the trial could support approval in the first half of 2016.
But with estimated 2020 sales of $165m for reveglucosidase alfa and $75m for cerliponase alfa, neither will make up for the failure of drisapersen if the latter gets the eventual thumbs down from the FDA.
Argos eyes renal cancer approval
At just $77m, Argos’s market cap does not exactly inspire confidence, and neither does its lead asset, following as it does in the footsteps of Dendreon’s prostate cancer flop Provenge, the first personalized immunotherapy.
But before rocapuldencel-T can even count itself in this not-so-illustrious company it first has to prove its worth in the phase III Adapt trial, which is comparing the drug plus Sutent versus Sutent alone with a primary endpoint of overall survival.
A second interim analysis is due by the end of the year, with a third slated for mid-2016, around the time of the Asco meeting. Positive results could see the trial stopped early.
Bullish analysts believe rocapuldencel-T can replicate its performance in a phase II study that found an overall survival of 57 months in intermediate-risk patients, double what was expected. Around 75% of patients in Adapt fall into this category.
Even if it lives up to these expectations, if approved rocapuldencel-T could face the same problems as Provenge, which was overpriced and cumbersome to deliver. But some analysts contend that Argos has learned from Dendreon’s woes and improved manufacturing processes to keep costs down. It should also help logistically that rocapuldencel-T has a two-week shelf-life compared with 18 hours for Provenge.
Then there is the issue of competition, not least from Bristol-Myers Squibb’s PD-1 inhibitor Opdivo, which in November added second-line renal cell carcinoma to its impressive list of approvals (US regulator slows down the immuno-oncology runaway train, November 30, 2015). Exelixis’s Cometriq is also looking like a contender in second-line disease.
In first-line RCC, where rocapuldencel-T is being trialled, Opdivo is again in the mix, this time in combination with Yervoy. Roche’s PD-L1 inhibitor atezolizumab, given alongside Avastin, completes the phase III players (Therapeutic focus – Opdivo and Cometriq tussle in kidney cancer, October 05, 2015). There is also the potential for rocapuldencel-T to be combined with anti-PD-1/PD-L1 drugs, some analysts believe.
With its fast dwindling pile of cash, Argos is going all in on rocapuldencel-T. In spite of the issues, positive results from Adapt could help it reel in a partner – but negative data could kill the company off.
|Cerliponase alfa||Phase I/II trial in CLN2 disease||NCT01907087|