Aerovate's shares plummet as inhaled version of Novartis' Gleevec misses the mark in PAH trial

Aerovate Therapeutics’ attempt to use an inhaled formulation of Novartis’ cancer med Gleevec as a treatment for pulmonary arterial hypertension (PAH) didn’t pan out.

After the drug missed the mark in a phase 2b study, Aerovate’s stock price plummeted 93.3% during Monday’s trading. 

The study, called IMPACHT, tested three different doses of a dry powder inhaled version of imatinib in PAH patients. While the drug was well tolerated, it didn’t cause an improvement in pulmonary vascular resistance compared to placebo, Aerovate reported in a press release.

The drug was a failure through and through. It didn’t make for “meaningful improvements” in the secondary endpoint of change in six-minute walk distance, nor did it hit “several” other secondary endpoints.

Based on the results, the company is putting the breaks on enrollment and shutting down its phase 3 portion of the study. A long-term extension study will also be scrapped.

“The results of the Phase 2b portion of IMPAHCT was unexpected and disappointing,” CEO Tim Noyes said. “Our immediate focus is on transparently sharing these findings with investigators, patients and the PAH community.”

Aerovate will spend the upcoming weeks communicating with the study advisory committee and the wider PAH community to “thoroughly discuss these data and their implications,” Noyes added.

The downfall of Aerovate’s lead and only clincial program could be disastrous for the company. As of Friday, the PAH-focused drugmaker is running on some $100 million of cash, cash equivalents and short-term investments, according to the release.

Despite imatinib’s flop, Leerink Partners analysts saw little implication for Gossamer Bio’s focus and lead candidate seralutinib. Even though both drugs are inhaled PDGFR inhibitors, the two compounds have different kinase inhibition profiles.

“Since seralutnib was designed to inhibit multiple kinases that play a role in the pathology of PAH, we believe this could translate to different outcomes in the clinic,” Leerink analysts wrote in a Monday note to clients.

Gossamer is testing seralutnib in PAH in the phase 3 PROSERA trial, with a potential readout in late 2025. Imatinib’s setback could free up more PAH patients for Gossamer to enroll, the Leerink team noted.

Novartis’ Gleevec, a tyrosine kinase inhibitor (TKI), has been marketed since 2001 and is indicated to treat several rare cancer types including chronic myeloid leukemia (CML). As the first approved TKI, the drug is credited with transforming the life expectancy for CML patients to that of the general, cancer-free population and opening the door to other TKIs such as AstraZeneca’s Tagrisso.

Sun Pharma launched the first Gleevec generic back in 2016. According to Aerovate, imatinib has shown clinical efficacy in phase 2 and 3 PAH trials when administered orally but was not approved due to “systemic” side effects. The dry powder form was meant to skirt systemic exposure by delivering the therapy directly to the lungs.