Developers partnering on easier-to-use drug formulation for myelofibrosis

Halozyme Therapeutics and Incyte are partnering to develop an under-the-skin (subcutaneous) formulation of INCA033989, Incyte’s therapy candidate for people with myeloproliferative neoplasms, including myelofibrosis — a type of slow-growing blood cancer.

The goal for the two U.S.-based developers is to create a simpler and potentially more convenient way for those with myeloproliferative neoplasms caused by CALR gene mutations to receive the experimental treatment. The companies also plan to use Halozyme’s ENHANZE drug delivery technology to develop additional subcutaneous formulations of INCA033989.

Thus far, INCA033989 has been developed for intravenous, or into-the-vein, administration. The therapy was evaluated in two early clinical trials — the Phase 1 studies NCT05936359 and NCT06034002 — and recent results showed it was generally safe and significantly reduced myelofibrosis symptoms. 

Now, the companies want to make it easier to administer, according to a press release from Halozyme announcing the collaboration

“Incyte brings a strong portfolio and deep expertise in hematology [blood diseases], and we look forward to working together to enable the development of more convenient subcutaneous treatment options for patients,” said Helen Torley, Halozyme’s president and CEO.

In parallel, Incyte is comparing the safety, tolerability, and pharmacological properties of INCA033989 in healthy adults in a Phase 1 trial (NCT07448155) in the U.S. That study is being conducted at a single site in Arizona, and is expected to wrap up later this year.

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Myelofibrosis is a myeloproliferative neoplasm, a type of blood cancer that usually grows slowly. It occurs when the bone marrow— the spongy tissue found in the center of most bones — produces abnormal blood cells, leading to inflammation and scarring, or fibrosis. This can prevent the bone marrow from producing healthy blood cells, leading to symptoms such as an enlarged spleen, fatigue, and easy bruising.

In most people with myelofibrosis, cancer cells have disease-driving mutations, including in the CALR gene. These mutations account for about one-quarter of cases of primary myelofibrosis, when the disease develops without an underlying condition linked to it.

Collaboration aims at exploring ways to deliver drug to patients

INCA033989 is an antibody-based therapy that targets mutated calreticulin, the protein encoded by the CALR gene that helps maintain calcium homeostasis within cells. The goal of the new collaboration is not to change how INCA033989 works, but to explore a different way of delivering it to patients, according to the companies.

The ENHANZE drug delivery system uses a lab-made version of a naturally occurring enzyme called hyaluronidase. After injection under the skin, the enzyme temporarily breaks down hyaluronic acid, a substance that helps maintain tissue structure. This creates space for larger amounts of medicine to spread through the tissue and enter the bloodstream before the area naturally returns to normal.

The two Phase 1 trials are testing INCA033989 intravenous formulations in people with myelofibrosis or essential thrombocytopenia, another type of myeloproliferative neoplasm. In both studies, the investigational therapy is given intravenously, either alone or in combination with Jakafi (ruxolitinib), an oral JAK inhibitor approved for the treatment of myelofibrosis.

In myelofibrosis, INCA033989 was tested as a standalone treatment in people whose disease did not respond adequately to, or who could not tolerate, previous JAK inhibitor therapy. It was also evaluated in combination with Jakafi in patients whose disease remained insufficiently controlled with Jakafi alone.

The results, recently presented by the company, showed that INCA033989 led to clinically meaningful improvements in disease measures in both treatment groups. More than half of the participants achieved at least a 25% reduction in spleen volume, and about one-third achieved a reduction of 35% or greater.

After six months, about one-third of patients experienced a 50% or greater reduction in symptom burden. Reductions in anemia, marked by low red blood cell levels, were also observed in 60% of patients receiving INCA033989 alone and 35% of those receiving the combination therapy.

Beyond reducing disease symptoms, INCA033989 also appeared to reduce the proportion of blood cells carrying the mutated CALR gene.

INCA033989 was generally well tolerated, with about 80% of the patients remaining on treatment at the time of the analysis. Most participants experienced some side effects during treatment. The most common serious complications were low blood cell counts, including anemia.

Under the new agreement, Halozyme will receive an upfront payment and may receive additional milestone payments and royalties if the treatment formulation developed using ENHANZE reaches commercialization. Incyte may also select up to two additional targets for future use with this technology.