Ready to rival J&J, Takeda's growth plan bears fruit with FDA nod for niche lung cancer drug Exkivity

Takeda has been hoping its Wave 1 pipeline of medicines can drive near-term growth, but the group has been through a rough patch lately. With an FDA go-ahead for a niche lung cancer drug, the Japanese pharma has finally scored a regulatory win and has its chance to challenge Johnson & Johnson.

The FDA granted conditional approval to Takeda’s Exkivity, or mobocertinib, for treating non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations after progression on or after platinum-based chemotherapy, the company said Wednesday.

EGFR exon 20 disease makes up 1% to 2% of all NSCLC cases, or about 2,000 to 4,000 patients per year in the U.S., Dion Warren, Takeda’s head of the company's U.S. oncology business unit, said in an interview ahead of the approval. Takeda has projected peak sales of $300 million to $600 million for the medicine.

EGFR exon 20-mutated NSCLC patients typically respond poorly to other EGFR inhibitors such as AstraZeneca’s Tagrisso as those drugs aren’t specifically designed to target this disease subtype. It was only in May that Johnson & Johnson’s bispecific antibody Rybrevant became the first FDA-approved drug for the patient group.

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For a rare cancer type that didn’t have effective targeted therapies until recently, Takeda’s initial marketing strategy focuses on driving accurate diagnosis and physician education, Warren said. Diagnosis can be a challenge, and increasing awareness for this patient population takes time, he acknowledged. Exkivity represents Takeda’s second targeted lung cancer drug, coming after Alunbrig for ALK-positive disease. Thanks to that prior launch, the company can at least spare the trouble of building a physician network from scratch.

Alongside the Exkivity nod, the FDA has simultaneously approved an NGS companion diagnostic by Thermo Fisher, which Takeda said can enable more accurate diagnoses than PCR testing.

Besides Takeda's efforts to find patients, the company's new drug also needs to compete with J&J's Rybrevant. By looking at early tumor shrinkage data, the Takeda drug appears to be the underdog.

In a phase 1/2 trial, Exkivity triggered a response in 28% of post-chemo EGFR exon 20 insertion patients by analysis of an independent data review committee, or 35% by investigator evaluation, according to an update in February. By comparison, Rybrevant has reported a response rate of 40% in its own early-stage trial.

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During the interview, Takeda’s head of oncology global medical affairs, Awny Farajallah, M.D., pointed to Exkivity’s duration of response as one data point that stands out in favor of the med. Patients on the Takeda drug experienced responses lasting a median 17.5 months per independent review, while Rybrevant’s median duration of response came in at 11.1 months in their separate trials. Exkivity helped patients lived a median 7.3 months without disease progression, versus 8.3 months for Rybrevant.

“This is pretty exceptional in this patient population because the background before targeted treatments like [Exkivity] you’re looking at two to four months of progression-free survival,” Warren said.

The two drugs’ ability to extend life appears similar, as Exkivity patients lived a median 24 months, compared with 22.8 months for Rybrevant.

On the downside, Exkivity is linked to a higher rate of serious side effects. One common side effect was diarrhea, which appeared in over 20% patients. For the phase 1/2 trial that earned Exkivity its FDA go-ahead, Takeda just added two more cohorts in May with extra antidiarrhea prophylaxis measures.

Takeda amended its protocol so that it can “ensure that there are adequate protocols for diarrhea management and prevention … so the patient can get the maximum benefit out of the medicine while managing the adverse event,” Farajallah said.

Exkivity’s safety profile is “very consistent” with other oral EGFR inhibitors, so physicians are already accustomed to managing these side effects within the drug class, Warren added.

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In the meantime, both Takeda and J&J are pursuing approvals in newly diagnosed NSCLC with EGFR exon 20 alterations. The phase 3 EXCLAIM-2 trial is pitting Exkivity against chemo in the front-line setting, and the trial could read out first data in 2022.

J&J is taking a different path for Rybrevant’s phase 3 study. In the phase 3 PAPILLON trial, its Janssen unit is pitting the combination of Rybrevant and chemo against chemo alone for exon 20 patients. Separately, the MARIPOSA trial combines Rybrevant with Yuhan-partnered small-molecule EGFR inhibitor lazertinib—which in January won approval in South Korea as Leclaza—against Tagrisso in the broader exon 19 and exon 21 mutation group.

Exkivity is part of Takeda’s Wave 1 pipeline, which includes about a dozen products the company hopes can bring in about $10 billion in aggregate peak sales. But the group of meds has suffered setbacks lately. A concentrated immunoglobulin drug Takeda developed with CSL Behring failed to move the needle in hospitalized COVID-19 patients. Just a few days ago, pevondedistat flunked in a phase 3 blood cancer trial.

In addition, Eohilia has its FDA decision for eosinophilic esophagitis mysteriously delayed with no known action date. And European authorities recently converted an application for dengue vaccine TAK-003 from a fast track to regular review.