Celcuity Data, Cardiff Expectations, and Apellis Approval

What a week and it's only Monday.

Word Count: 2,007 words, Reading Time: 10 minutes

Hello all. I’m writing this late on Monday, July 28 hopefully able to get it to you on Tuesday morning July 29. I have a lot of topics I want to cover so going to go very quickly.

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Celcuity Data

Today was an exciting day for me as well as for some patients and providers. After writing about CELC 0.00%↑ and their drug gedatolisib for almost two years, today they released their first Phase 3 data and it exceeded even my lofty expectations. The data was in 2L HR+/HER2-/PIK3CA advanced breast cancer. I know the segmentation in breast cancer can be confusing but what is important is there are over 20,000 patients affected that didn’t have a lot of good options prior to this.

I expected Arm C above, the standard of care arm, to produce median Progression Free Survival of 3 months or possibly less but for margin of error I went with three months. For Arm A, the arm with three drugs I thought based on the (messy) Phase 1b previous data there would be 7 to 9 months of Progression Free Survival. But I honestly wasn’t incredibly confident as the Phase 1b was single arm, open label, had different inclusion criteria, different dosing regimens, differing mutation statuses, and multiple arms with results ranging from PFS of 5.1 months to 12.9 months. My guess was honestly closer to 7 months mPFS for the “triplet” in this Phase 3 since open label data usually resolves to the less impressive side of the spectrum when put in a randomized controlled trial. The Phase 1b data is shown below if you are curious.

(And yes it’s confusing that they name all the arms of their trials as letters. All future lettering after the below image will refer to the arms in the Phase 3.)

I thought if the triplet arm had 7 months mPFS and the control was 3 months well that’s a delta of 4 months which exceeds the delta of 3 months needed to be clinically significant per the company and FDA and it would be a solid idea. But I wasn’t completely resolute in my confidence that it would work. In fact, most people I talked to were negative about it and it kind of knocked me off my game. The Phase 1b data was messy so I was cautiously optimistic going into data but didn’t have it as a Top 10 position.

The real results knocked it out of the park with the triplet (Arm A) achieving 9.3 months of mPFS compared to 2.0 months for fulvestrant alone (Arm C). Even the gedatolisib-containing doublet (Arm B) achieved 7.4 months compared to 2.0 months. Again, the company said a delta of 3 months would be clinically significant. I thought 6 months delta would honestly be a dream scenario. The real delta was 7.3 months. Look at those hazard ratios below.

And look at hazard ratios from other 2L trials, probably the best way to do cross trial comparisons of benefit.

Also with even the doublet achieving 5.4 months of separation, it’s clear that gedatolisib is driving the benefit and not just sensitizing for retreatment with a CDK4/6 inhibitor so the contribution of components argument can be put to rest as well. This drug is very active, this drug is first-in-class, this drug is best-in-class, and additionally this drug appears to be safe and well-tolerated although we don’t have the full safety database until the final presentation at a medical conference. The two biggest worries with this drug based on the class and Phase 1b data were hyperglycemia and stomatitis, and both appear to be happening at a lower rate than the Phase 1b data. I would have like to see the incidence of Grade 3 hyperglycemia and Grade 3 stomatitis (the latter which should be low due to the inclusion of a manadatory medicated mouthwash rinse procedure) but still the company went out of their way to mention these two things clearly to ease investor anxiety without giving away data that they believe is embargoed for a medical meeting.