Misery In Myelofibrosis: Pacritinib Setback A Boost For Jakafi
Executive Summary
With the commercial opportunity in the myelofibrosis market expected to double to over $1bn in the next five years, competition to Incyte/Novartis's Jakafi seems further away than ever as CTI BioPharma pulls the European regulatory filing for pacritinib.
The European Medicines Agency has revealed that CTI BioPharma Corp. has withdrawn its application for marketing authorization for Enpaxiq (pacritinib) for treating patients with an enlarged spleen or other symptoms of myelofibrosis. With only Incyte Corp./Novartis AG's JAK1/JAK2 inhibitor Jakafi/Jakavi (ruxolitinib) approved specifically for the indication, this is a real setback for patients.
However, the news is not a big shock as drug development in the myelofibrosis space is notoriously fraught, and pacritinib in particular has had a tumultuous development history to date.
The US FDA issued a full clinical hold on pacritinib, an investigational oral JAK2/FLT3 inhibitor, in February 2016 because of concerns about excess mortality and other adverse events, including intracranial hemorrhage, cardiac failure and cardiac arrest, in the company's two Phase III studies, PERSIST-1 and PERSIST-2. (Also see "CTI/Baxalta Withdraw Pacritinib NDA Following More Deaths" - Scrip, 10 Feb, 2016.) and (Also see "CTI BioPharma’s Pacritinib Meets One Co-Primary Endpoint, Just Misses Another, In PERSIST-2" - Scrip, 30 Aug, 2016.)
This hold was lifted in January this year after CTI provided, among other items, final clinical study reports for both the PERSIST trials and a dose-exploration clinical trial protocol that the FDA requested. The new trial, PAC203 plans to enroll up to around 105 patients with primary myelofibrosis who have failed prior ruxolitinib therapy to evaluate the safety and the dose response relationship for efficacy (spleen volume reduction at 24 weeks) of three doses: 100 mg once-daily, 100 mg twice-daily (BID) and 200 mg BID. The 200 mg BID dose regimen was used in PERSIST-2. The company expects to start the trial in the second quarter of 2017.
However, in its official communication with the EMA's CHMP committee, CTI does not mention conducting a new trial.
According to CTI, the European withdrawal is based on the fact that in order to answer the Day 120 questions put forward by the regulator, the company "will need to integrate into the dossier the data from the second pivotal Phase III study, PERSIST-2 [and] there is insufficient time to complete this within the required CHMP timeframe."
The myelofibrosis space is marked with a series of high profile development setbacks, including Gilead Sciences Inc.'s JAK 1/2 inhibitor momelotinib (Also see "Gilead's Late-Stage R&D Misfire Gives Respite To Competing Myelofibrosis Therapies" - Scrip, 17 Nov, 2016.), Geron Corp./Janssen's telomerase inhibitor imetelstat (Also see "Imetelstat Study Blip Beats Geron’s Shares Down" - Scrip, 14 Sep, 2016.) and Sanofi's JAK 2 inhibitor fedtratinib which failed in 2013.
Myelofibrosis, which is closely related to blood cancers, is a life-threatening bone marrow disorder caused by the accumulation of malignant bone marrow cells that triggers an inflammatory response and scars the bone marrow, limiting its ability to produce red blood cells and prompting the spleen and liver to take over this function. Symptoms include enlargement of the spleen, anemia, extreme fatigue and pain. It is believed there are around 18,000 patients with the condition in the US.