I always read stories about new drugs with great joy. That there are scientists and companies dedicated to developing drugs that keep us alive is very inspiring. The naysayers will quote share values and profit margins but all that matters to me are those 2 little tablets (dasatinib) that I take each morning that keep me alive.
If this product comes to market let’s hope NICE don’t stop access to this drug too.

Ariad Pharmaceuticals is to expand into Europe following promising results for an investigational cancer drug.

The US biotech firm will site a European HQ in Switzerland to support the planned filing of ponatinib, a pan-BCR-ABL inhibitor which has performed well in chronic myloid leukemia (CML) patients in clinical trials.

Talking to Pharmafocus, Ariad’s president of R&D and chief scientific officer Tim Clackson said the Swiss office would be open “imminently”.

Ponatinib is the Cambridge, Massachussetts-based oncology specialist’s lead candidate and is expected to be filed with US and European regulators before September this year.

If approved it would be up against tyrosine kinase inhibitors (TKIs) such as Novartis’ Glivec (imatinib), Novartis’ Tasigna (nilotinib) and Bristol-Myers Squibb’s Sprycel (dasatinib).

But Ariad is confident ponatinib’s mode of action is different from these brands as it bypasses T315I, the so-called ‘gatekeeper’ mutation in CML and can treat patients with all mutations – or none at all, a group Clackson says are “the most difficult to treat”.

The product was developed from the ground up with exactly that function in mind, part of Ariad’s use of computational chemistry approach which Clackson says brings in “the building blocks to sculpt the drug exactly as we want”.

Many CML sufferers develop resistance to TKIs over time, but in the recent PACE trial patients at all stages of the disease had a positive clinical response to ponatinib.

It saw 54% of patients achieving a major cytogenetic response (MCyR), with 44% a complete cytogenetic response (CCyR). The median follow-up for chronic CML patients is 10.1 months.

Of those patients with the T315I mutation, 70% achieved a MCyR with 66% a CCyR.

When it came to the higher bar of measurement, 30% of chronic-phase patients achieved a major molecular response (MMR), something 50% of chronic patients with the T315I mutation also attained.

A phase III trial pitting ponatinib against Glivec is planned for the third quarter of the year.

CML is a cancer of the white blood cells which affects around 7,000 patients each year in Europe. “T315I was a death sentence,” says Clackson. “Now there’s another approach.”

Switzerland chosen as European base

Ariad is currently building a sales force and commercial infrastructure in the US and will be mirroring it in Europe, with “small” sales teams in the UK and other key European markets.

There are no plans for any R&D to be based on the continent. “We’ll continue to manufacture at various third parties in the US and Europe,” Clackson said.

The Swiss facility will be in the canton of Vaud, where Ariad “will be looking to establish scientific connections with universities, research institutes and hospitals”.

Tax incentives were one of the key reasons, along with pharmacological expertise and a skilled workforce, for choosing Switzerland over other European locations, Clackson says.

Ariad’s most high profile drug discovery before this was oral mTOR inhibitor ridaforolimus, for which two years ago Merck acquired the exclusive license for oncology indications.

Ponatinib has also attracted the attention of other pharma companies but Ariad has decided to develop and commercialise the drug itself.

“We had incredible interest in partnering,” says Clackson. “We had very, very substantial offers on the table. But it was an unequivocal decision to go it alone.”

Ariad’s other pipeline products include AP26113, an oral, dual inhibitor of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR), which is to be developed in non-small cell lung cancers.

The company also has AP1903, which is being evaluated in patients with prostate cancer and is licensed to Bellicum Pharmaceuticals.

Adam Hill
Published on 29/06/12