Upcoming events: Alnylam and Biogen readouts plus decision time at the CHMP meeting

Welcome to your weekly digest of approaching regulatory and clinical read outs. Phase II data on Alnylam’s biggest hope ALN-TTR02, for hereditary amyloidosis, are expected on June 30 at the Peripheral Nerve Society meeting. Meanwhile, the results of ALN-TTRsc in phase I are also expected shortly, which will be the first test of its subcutaneous delivery route, key to the company’s future pipeline.

Biogen Idec will report full data on its clotting factors rFVIIIFc and rFIXFc at the International Society on Thrombosis and Haemostasis meeting. This should give some idea on dosing, which both specialists and patients will be eagerly watching. Lastly, the European Medicines Agency's human drugs panel is expected to meet next week; both Raptor Pharmaceutical's Procysbi and Takeda's Nesina have achieved US approval and are now looking to match this in Europe.

Alnylam: ALN-TTR02 and ALN-TTRsc

Alynlam’s ALN-TTR02 uses RNA interference to silence a protein called transthyretin (TTR). In hereditary amyloidosis, a genetic disease, mutations in TTR cause it to misfold, leading to accumulation in tissues (Therapeutic focus – Amyloidosis options emerging from Pfizer, Alnylam, May 31, 2012).

ALN-TTR02 is indicated for the treatment of familial amyloid polyneuropathy (FAP) when TTR accumulates in the peripheral nerve tissue, causing wasting and a loss of nerve function.

Top line, multi-dose data in 20 patients with TTR amyloidosis is expected at the PNS meeting, which is taking place June 29 - July 3 in St. Malo, France. The patients were dosed every four weeks with intravenous infusion. After the phase I results last July, Alnylam's shares jumped 53%. The trial in 17 healthy volunteers showed that serum TTR protein levels were reduced by up to 94% (Alnylam pushes forward in amyloidosis after Pfizer set back, July 16, 2012).

Leerink Swann analysts see little risk in the data readout, with Deutsche Bank noting a 75% probability of success. Sales are forecast to reach $301m by 2018 according to EvaluatePharma. In the second half of the year both a phase II extension trial and pivotal phase III trial are expected to start.

Despite the bright looking prospects, long term safety data is likely to be key for Alnylam’s compounds to differentiate from competitors. Pfizer’s Vyndaqel was approved in Europe for FAP, but received a complete response letter in the US, with the regulator requesting a second efficacy study. Meanwhile, ISIS-TTRRx from GlaxoSmithKline and Isis Pharmaceuticals started a phase II/III study in FAP patients earlier this year, which is looking to recruit 195 patients.

Also expected in the coming months is phase I data with ALN-TTRsc. It is indicated for the treatment of familial amyloid cardiomyopathy (FAC), where TTR accumulates in the heart muscle, leading to cardiac failure.

The phase I trial is looking to recruit 40 healthy volunteers and is a single- and multi-dose escalation study. ALN-TTRsc will be delivered subcutaneously. Analysts note that the results are key because it is the first human study using the GalNAc subcutaneous delivery technology, and Alnylam’s future pipeline, including opportunities such as haemophilia (ALN-AT3) and porphyria (ALN-AS1) are based on this technology.

While Deutsche Bank analysts believe there is a 30% probability of success, they note the larger market opportunity for FAC - the prevalence is roughly four times greater than FAP. A phase II trial in FAC is expected to start at the end of 2013.

Biogen Idec: rFVIIIFc, rFIXFc

The ISTH meeting is taking place from June 29 – July 4 in Amsterdam, The Netherlands. The trials of rFVIIIFc in haemophilia A and rFIXFc in haemophilia B, called A-Long and B-Long, respectively, both reported positive phase III results late last year (Biogen’s blood data prove a little anaemic for some investors, November 1, 2012).

Leerink Swann analysts note that data at the meeting will be important because PK was measured on each enrolled patient, and the full data should give a much clearer idea of what the drugs are capable of achieving in terms of dosing, which is vital to these drugs’ success.

Committee for Medicinal Products for Human Use meeting June 24-27

The June CHMP meeting is taking place next week, and the following projects awaiting European decisions in mid 2013 could be discussed at the meeting.

Raptor Pharmaceutical's Procysbi was approved in the US for ultra-orphan disease nephropathic cystinosis, an inherited condition that causes the buildup of cystine, which leads to irreversible tissue and organ damage.

Leerink Swann analysts note that the European approval is likely given the FDA approval. In the US Procysbi will be priced at roughly $250,000 a year. However, Raptor will find the reimbursement issue in Europe a much tougher battle (After Procysbi approval the pricing battle begins, May 1, 2013).

Nesina (alogliptin), Takeda’s DPP-IV inhibitor, is also approved in the US with expected launch in December. Indicated for Type 2 diabetes, the drug is the company’s biggest growth driver and had $457m worldwide sales in 2012. It is forecast to reach $1.1bn by 2018, according to EvaluatePharma.

The entry of generic Actos hit Takeda's sales hard; the diabetes drug reported sales of $1.5bn last year, a 60% loss on 2011, and is forecast to drop to $470m for 2013, according to EvaluatePharma. Takeda needs to offset this and look to maintain its diabetes franchise; the US launch of Nesina and European approval would help achieve this.

All information is sourced to analyst notes and the EvaluatePharma Calendar of Events tool.

To contact the writer of this story email Joanne Fagg in London at [email protected] or follow  @JoEPVantage on Twitter