Iovance hammered as cell therapy disappoints
Lower – and shorter – efficacy add to serious doubts about the TIL therapy's future.
Today Iovance can proudly say it is not an Asco faller – but only because the poor data on its cell therapy lifileucel in melanoma, which wiped 63% off the company’s market cap in early trade today, were not actually released at the meeting.
Lifileucel is Iovance’s lead tumour-infiltrating lymphocyte (TIL)-based therapy, and already faces major problems in that the cells are difficult to standardise, as well as production being expensive and time-consuming. To be commercially viable, lifileucel needs to show knockout data. It has not.
The new cut comes from cohort 4 of the phase 2 C-144-01 study in a population with advanced disease. Patients in the trial have unresectable or metastatic melanoma and had progressed on prior anti-PD-1/L1 therapy, and if Braf mutation positive, also on prior Braf or Braf/Mek inhibitor therapy.
The results show a clear decline in lifileucel’s efficacy. Objective response dropped from the 36.4% seen in cohort 2 of the trial, released at the 2020 Asco meeting, to 29%. Fewer complete responses also alarmed investors – but the main cause of distress seems to be the shrinking duration of response to the therapy.
|Data from Iovance's C-144-01 clinical study of lifileucel (NCT02360579)|
|Cohort 2||66||36.4||5||18||Not reached at median follow-up of 36.6mth|
|Pooled data from cohorts 2 and 4||153||31||8||40||Not reached at median follow up of 27.6mth|
|ORR = Objective response rate. CR = complete response. PR = partial response. DOR = duration of response. Source: company release.|
Iovance offered several explanations for the poor showing. Patients in cohort 4 had more severe disease than those in cohort 2, it said, as well as higher baseline levels of lactate dehydrogenase (a negative prognostic factor) and higher lesion counts. They had also received anti-PD-1 treatment for longer.
Further data from Cohorts 2 and 4 ought to come at a medical meeting in the second half of 2022, and the much-delayed BLA filing for lifileucel in melanoma is set for August.
The company insisted on a conference call yesterday that the 10.4 months duration of effect is very meaningful, and that monotherapy or doublet chemo yields duration of response “as low as three and a half months”.
Stifel analysts wrote that the durability pullback was “especially surprising”. They believe that the project’s chances of approval are unchanged by the new data – they give it a probability of success of 65% – but see little usage should it reach the market. They slashed their estimate for market penetration at peak from 30% to 15%.
Iovance must now cling on to hope for better outcomes in ongoing phase 2 trial in patients with melanoma, head and neck squamous cell carcinoma or non-small cell lung cancer, one arm of which is testing a combination of lifileucel with Keytruda. If this combination can show decent efficacy the TIL might still have some commercial appeal.
But this trial has already yielded disappointing data, again on durability, in lung cancer patients.
Iovance has $516m in the bank, which it maintains is sufficient to launch lifileucel, and management denied that a cash raise is in the offing. But the share price is at a five-year low, and the company really needs to get the project over the line. Now the chances of that happening look shakier than ever.