A little more than two months after completing enrollment, an interim analysis shows Kadmon Holdings Inc.'s pivotal trial of ROCKstar (KD-025-213) testing KD-025 in patients with chronic graft-vs.-host disease (cGVHD) met its primary endpoint of overall response rate.

Harlan Waksal, president and CEO, Kadmon

"They are knock-your-socks-off type of results," Harlan Waksal, Kadmon's president and CEO, said on an investor call. "I'm pleasantly thrilled by response rates in the 60 percent range."

ROCKstar is an ongoing open-label study of adults and adolescents with cGVHD who have received at least two prior lines of systemic therapy. About 126 subjects in the randomized, parallel assignment, multicenter study were divvied into two arms, either taking 200 mg of KD-025 daily or taking it twice daily.

KD-025 showed statistically significant overall response rates (ORRs) of 64% with KD-025 200 mg once daily (QD) (95% Confidence Interval (CI): 51%, 75%; p<0.0001) and 67% with KD025 200 mg twice daily (BID) (95% CI: 54%, 78%; p<0.0001). KD-025, a selective oral inhibitor of Rho-associated coiled-coil kinase 2, was well-tolerated and adverse events have been consistent with those expected in the patient population.

Waksal said the company will share the data with the FDA at a pre-NDA meeting by March 2020 to discuss timing for a regulatory filing.

The company's stock (NYSE:KDMN) closed up 23.4% on Tuesday at $3.69 per share.

GVHD occurs in stem cell transplants when a donor's T cells attack a patient's healthy cells. The condition can be mild, moderate, severe or life-threatening. No standard regimen exists for prevention and combinations of medications are used. As one of the leading causes of medical problems and death after transplant, cGVHD typically involves a single organ or several organs. The acute form (aGVHD) usually develops within the first 100 days after transplant. It may affect the skin, gastrointestinal tract or liver.

Incyte Corp. recently posted fresh data from one of a trio of phase III trials across cGVHD and aGVHD. Just last month, it had positive results from the Novartis AG-sponsored pivotal phase III Reach 2 study evaluating ruxolitinib (Jakafi) in patients with steroid-refractory aGVHD. The study met its primary endpoint of improving ORR at day 28 with ruxolitinib treatment compared to best available therapy.

The other Incyte studies are in steroid-refractory cGVHD, dubbed Reach 3, and the experiment with another JAK inhibitor, itacitinib, in treatment-naïve aGVHD, known as Gravitas-301. Reach 3 data are expected by the end of this year. Gravitas-309 was initiated in January with results expected in 2021. (See BioWorld, July 26, 2019.)

Also in the mix for aGVHD prophylaxis is Dublin-based Jazz Pharmaceuticals plc, which is testing defibrotide in a prospective, randomized, open-label phase II study of the efficacy and safety of defibrotide added to standard-of-care immunoprophylaxis for the prevention of aGVHD, compared to the standard of care alone. Jazz expects to enroll about 150 adult and pediatric patients who have undergone allogeneic hematopoietic stem cell transplant (HSCT) from an unrelated donor. The primary endpoint is cumulative incidence of grade B-D aGVHD by day +100 post-allogeneic HSCT.

Further analysis of the safety and efficacy data is ongoing. Novartis expects to initiate discussions with ex-U.S. regulatory authorities in 2020, and to submit Reach 2 results for presentation at an upcoming scientific meeting.

Kadmon plans to commercialize the drug itself, Waksal said, noting initial conversations it has already had with the EMA. The FDA granted breakthrough therapy and orphan drug designation to KD-025 to treat cGVHD.

On the conference call, Waksal said he was pleased to see the ROCKstar ORRs not differ much from Kadmon's ongoing phase II of KD-025 in patients with previously treated cGVHD. Recently updated data showed ORRs of 65%, 63% and 52% in cohort 1 (200 mg QD; n=17), cohort 2 (200 mg BID; n=16) and cohort 3 (400 mg QD; n=21), respectively. There was an ORR of 58% in patients with two or more prior lines of systemic therapy and 62% in patients with four or more organs involved.

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