Tukysa’s Trial Success Spurs Roche’s Kadcyla and Pfizer’s $43B Acquisition

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Tukysa's Trial Success Spurs Roche's Kadcyla and Pfizer’s $43B Acquisition

Pfizer’s strategic move to acquire Seagen for $43 billion is primarily motivated by the Seattle biotech’s advantage in the field of antibody-drug conjugates (ADCs). However, the acquisition becomes even more appealing due to a recent triumph in a trial for a small-molecule cancer drug.

Seagen announced a significant breakthrough on Wednesday, disclosing that its phase 3 clinical trial involving a combination of its Tukysa and Roche’s Kadcyla has achieved its primary objective in patients with previously treated HER2-positive breast cancer. This combination therapy has demonstrated a notable reduction in the risk of tumor progression or death when compared to the administration of Kadcyla and a placebo. While data regarding patient survival is still in its early stages, Seagen intends to present detailed findings from the HER2CLIMB-02 trial at a medical conference and engage in discussions with the FDA.

These encouraging trial results play a pivotal role in reducing the risks associated with Pfizer’s acquisition of Seagen, as noted by analysts from Leerink Partners. Since its FDA approval in 2020, Tukysa has been utilized alongside trastuzumab (Herceptin) and chemotherapy for treating HER2-positive breast cancer that has metastasized after at least one prior treatment. Kadcyla, functioning as an ADC, employs Herceptin to guide a chemotherapy drug specifically to HER2-expressing cancer cells.

While ADCs generally exhibit greater potency than their corresponding antibody-based drugs, they do come with added toxicity concerns. In the HER2CLIMB-02 trial, patients receiving the Tukysa-Kadcyla combination reported more treatment discontinuations due to side effects compared to the control group. However, Seagen reassured that no new safety signals were detected by investigators.

The trial’s success underscores Tukysa’s ability to complement an antibody-drug conjugate, a significant finding in the increasingly competitive landscape of breast cancer therapeutics, according to the Leerink team. Both Tukysa and Kadcyla target HER2 and face competition from AstraZeneca and Daiichi Sankyo’s ADC Enhertu, which has already surpassed Kadcyla in a head-to-head trial.

One of Tukysa’s distinctive features, highlighted by Seagen, is its efficacy in controlling brain metastases—an advantage over its competitors. Dr. Roger Dansey, Seagen’s Chief Medical Officer, expressed optimism about the trial results, especially in patients with brain metastases.

With Tukysa’s demonstrated impact on progression-free survival (PFS), attention now turns to comparing the magnitude of improvement with Enhertu’s performance in this regard. The Destiny-Breast03 trial reported a substantial 67% reduction in the risk of progression or death for Enhertu compared to Kadcyla. While direct comparison should be approached cautiously due to varying patient populations and criteria, the Tukysa-Kadcyla combination demonstrated a median PFS of 8.2 months in a phase 1b trial.

The HER2CLIMB-02 trial outcome raises questions about whether Tukysa’s benefit could extend to Enhertu or Seagen’s own HER2 ADC, disitamab vedotin, developed in partnership with RemeGen.

Seagen’s development plan for Tukysa is comprehensive. It includes a phase 2 trial (HER2CLIMB-04) pairing Tukysa with Enhertu in second-line HER2-positive breast cancer and a phase 3 trial (HER2CLIMB-05) examining Tukysa in combination with Herceptin and Roche’s Perjeta as a first-line maintenance regimen. This evolving landscape underscores the pharmaceutical industry’s continued efforts to combat breast cancer through innovative therapies and strategic collaborations.