- Macrogenics said its experimental drug margetuximab, when combined with chemotherapy, helped previously treated patients with HER2-expressing metastatic breast cancer live 1.7 months longer than patients treated with Roche's Herceptin and chemo. The company has already disclosed that the biological drug reduced the risk of disease progression or death by 24%.
- Meanwhile, in a similar setting Puma Biotechnology's Nerlynx plus chemotherapy reduced the risk of disease progression or death by 24% when compared to Novartis' Tykerb plus chemo. Puma's benefit comes with an unwanted side effect — nearly one-quarter of patients taking it suffered severe diarrhea, even when taking an anti-diarrheal drug as a preventive.
- Both companies will present these data at the annual meeting of the American Society of Clinical Oncology, scheduled to run from May 31 to June 4. Release of abstract data lifted Macrogenics shares 10% and Puma 3% Thursday morning.
Once metastatic HER-positive breast cancer patients progress on treatment with Roche's mainstay drugs Herceptin (trastuzumab), Perjeta (pertuzumab) or Kadcyla (ado-trastuzumab emtansine), the standard of care is not clear.
Herceptin is still often used, but it has a low response rate, making oncologists eager for new treatment options.
In the SOPHIA trial, Macrogenics tested margetuximab in combination with chemotherapy directly against Herceptin and chemotherapy. The company had previously disclosed its progression-free survival benefit, but alongside the ASCO abstract release Wednesday the company also announced that it had seen preliminary signs margetuximab also keeps patients alive longer, by 1.7 months.
Not enough patients had died for the overall survival calculation to reach statistical significance. Nonetheless, it should give Macrogenics some confidence of being able to present a strong data package to the Food and Drug Administration when it seeks approval later this year.
While data showing margetuximab delays disease progression could be enough, overall survival remains a gold standard in regulatory review.
Roughly 85% of the patient population Macrogenics is studying carry a specific genetic signature — an allele known as C16A-158F — that is associated with diminished responses to drugs like Herceptin. In these patients, the risk of progression was reduced 32%, and the company says those patients lived 6.8 months longer than Herceptin patients in the preliminary overall survival analysis.
For Puma, which has struggled to find traction with its Nerlynx (neratinib) launch, any positive clinical news can be taken as good news. This came in the form of the delayed readout from the company's NALA trial, which could lead to expansion from Nerlynx's current approval: preventing HER-positive breast cancer from returning after a successful round of Herceptin.
The modest benefit seen in this setting, along with a side-effect profile that includes frequent episodes of severe diarrhea, has been a barrier to uptake, and disappointing sales for the first three months of 2019 recently prompted Cantor Fitzgerald analysts to downgrade their share price target from $57 to $20.
In advanced metastatic disease, Nerlynx plus capecitabine delayed progression or death when compared to Tykerb plus capecitabine, reducing the risk by 24%. The study missed on other endpoints, including objective response rate and overall survival, although it reduced the incidence of central nervous system metastases by a little more than 6 percentage points.
RBC Capital analyst Kennen MacKay wrote in a May 16 note to clients that the presentation at ASCO will likely focus on the "clinical meaningfulness" of the benefit, which in this setting is often measured by "palliative vs curative intent."
Based on the data provided, he estimated that the Nerlynx patients went two months longer than the Tykerb patients without progressing.