Upcoming events: FDA panel to examine candidates from Novartis and Rockwell

Analysis

Welcome to your weekly digest of approaching regulatory and clinical readouts. An FDA advisory panel will meet on November 6 to discuss Novartis’s panobinostat and Rockwell Medical’s Triferic. Novartis’s treatment would be a first-in-class option for multiple myeloma. However, the space is becoming increasingly competitive and panobinostat still needs to prove effective in combination with Revlimid, the current market leader.

Triferic, meanwhile, is an iron supplement for dialysis-dependent chronic kidney disease delivered as a dialysate. As well as treating iron deficiency, the company hopes to be able to claim that the product reduces the need for erythropoiesis-stimulating agents. This is likely to be a subject of much debate for the panel, as is the project's safety profile; Triferic has not been associated with hypersensitivity reactions, a problem for intravenous supplements.

Novartis: panobinostat

Farydak, the trade name for panobinostat, is an oral pan-inhibitor of histone and non-histone deacetylase enzymes – the first of its kind in multiple myeloma, which is a likely reason for the panel meeting. The proposed indication is in combination with Velcade (bortezomib) and dexamethasone, for treating patients who have received at least one prior therapy.

A phase III trial called Panorama-1 met its primary endpoint with a 37% improvement in progression-free survival. Further data released at this year’s Asco showed a median PFS of 12 months with panobinostat, bortezomib and dexamethasone versus eight months with bortezomib and dexamethasone (p<0.0001).

Adverse events led to discontinuation in 36% of the panobinostat patients compared with 20% in the control arm. Common grade 3/4 adverse events included thrombocytopaenia, neutropaenia and diarrhoea, which were all reported to be manageable.

The project has orphan designation in the US and Europe. If it receives a positive panel vote US approval could come before the end of the year; European approval is expected by mid-2015.

Entering the ring

According to consensus forecasts from EvaluatePharma 2020 sales are expected to hit $318m. However, the broad range in forecasts is noteworthy – from $162m to $551m. The asset has an NPV of $1.1bn, 1% of the company’s market cap.

The current market leader is Celgene’s Revlimid, which by 2020 is forecast to be selling $5.8bn, according to EvaluatePharma consensus. First-line therapy for multiple myeloma is often a combination of Revlimid or Takeda’s Velcade with dexamethasone. Patients who fail on either of these are likely to be given Amgen’s Kyprolis or Celgene’s Pomalyst.

JP Morgan analysts note that the Panorama-1 trial recruited patients who had not shown intolerance to Velcade, therefore panobinostat could be positioned ahead of treatment with Kyprolis or Pomalyst.

To make further headway in the market panobinostat will need to be tested in combination with Revlimid and dexamethasone versus those drugs alone. Novartis is recruiting a single-arm, 27-patient phase II trial combining panobinostat, Revlimid and dexamethasone, with data expected at the end of 2016.

Rockwell Medical Technologies: Triferic

In phase III Triferic, delivered as a dialysis fluid, arrested the decline of haemoglobin in kidney failure patients undergoing dialysis three to four times a week. The studies also showed that it can reduce patient use of erythropoiesis-stimulating agents (ESAs), used to stimulate red blood cell production in the bone marrow (Rockwell steels itself for review of iron supplement, September 9, 2013).

While Triferic is seen as having a good chance of getting backing as an alternative to IV iron, endorsement for an indication that specifies the reduction of ESAs is considered a tougher win. So any positive moves in this direction will be taken as an encouraging sign for the product's future.

On safety Triferic generated encouraging data: there were no cases of anaphylaxis or hypersensitivity reported in 48 weeks of treatment, and neither were there any cardiac events or cases of tissue iron overload. There was, however, an imbalance of deaths noted in one phase III trial, but none was declared to be treatment related.

The regulators will still pay close attention to Rockwell’s safety data as intravenous iron supplements carry the risk of toxic iron buildup and anaphylactic reactions.

For Michigan-based Rockwell, Triferic is considered a lead growth driver, with 2020 sales forecast to hit $342m, according to consensus from EvaluatePharma. A US action date is set for January 24, 2015.

Drug Study Trial ID
Panobinostat Panorama-1 NCT01023308
Triferic Prime (PhII)
Cruise 1 (PhIII)
Cruise 2 (PhIII)
NCT01286012
NCT01320202
NCT01322347

To contact the writer of this story email Joanne Fagg in London at joannef@epvantage.com or follow @JoEPVantage on Twitter

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