UPDATED: Q2 clear-out sees AstraZeneca dump gastric cancer, NASH PhIII studies

AstraZeneca London HQ

AstraZeneca ($AZN) has dropped 6 drug programs from its pipeline--with almost all the early-stage candidates being axed from its MedImmune biologics arms--in what is becoming the traditional attempt to quietly offload unwanted trials during a quarterly update.

First up, the company has ditched a Phase III combo trial of Epanova (omega-3-carboxylic acids), which is licensed to help lower triglyceride levels in adults with severe hypertriglyceridemia, and its SGLT2 inhibitor diabetes med Farxiga (dapagliflozin) that was seeking to treat the liver disease NASH, which has a number of biopharmas chasing what could be a $40 billion market.

It will also not continue the late-stage GOLD study of its marketed ovarian cancer drug and PARP inhibitor Lynparza (olaparib) in second-line gastric cancer. The writing had been on the wall as in May, Astra announced that the drug failed to meet its primary endpoint of improving overall survival when used with chemo, compared to chemo alone.

It had originally said it would be assessing these data, but has now clearly decided to cut its losses in this patient population.

And it doesn’t stop there. In its Q2 Astra also scrapped a number of NMEs from Phase I, all of which come from the locker of its MedImmune unit.

This included its experimental compound MEDI0639, a DLL-4 mAb for solid tumors. DLL4 plays an big role in vascular development and is widely expressed on the vasculature of normal and tumor tissues.

It also dropped a combo trial for its PD-L1 drug durvalumab (which recently gained an FDA "breakthrough" in bladder cancer) and MEDI6383, an OX40 agonist, also targeting solid tumors.

The OX40 agonist has shown antitumor efficacy in preclinical trials and is believed to have the ability to combine effectively with therapeutic cancer vaccines, as well as immuno-oncology targets. A Phase I for MEDI6383 on its own has also been culled.

And finally MEDI7836, an IL-13 mAb YTE asthma candidate, will also not be progressed. AstraZeneca has in Phase III an alpha-chain of the interleukin-5 receptor mAb for asthma in the form of benralizumab, although this did not come from MedImmune.

AstraZeneca gave little detail away in its release, listing simply those trials removed from its pipeline. But seeing as it bought MedImmune for more than $15 billion nearly a decade ago to bolster its early-stage pipeline, this clearing out of the early-stage closet can only be a painful experience.

In a statement to FierceBiotech, MedImmune said: “MedImmune’s innovative and sustainable pipeline is arguably one of the best in the industry. Biologics represent 50 percent of the overall AstraZeneca pipeline, with more than 120 biologics currently in development, including more than 40 in clinical development.

“As we’ve previously communicated, and as is typical in an early development program, we had three investigational OX40 assets in pre-clinical development, acknowledging that our strategy would be to bring one forward into clinical development, including:

·         MEDI5062 (humanized OX40 mAb)

·         MEDI6383 (OX40 fusion protein)

·         MEDI6469 (murine OX40)

“Each asset displayed slightly different biology, both in vitro and in vivo and we evaluated the unique characteristics of each molecule to better understand how they might provide the optimal response, both as monotherapy and in combination, in patients with cancer. Based on extensive research, we made the decision to move forward with MEDI5062, the humanized monoclonal antibody, and are very pleased with this molecule based on initial progression.  This is reflected in our updated clinical pipeline table.

“We are now focused on developing a comprehensive clinical trial program for MEDI0562 that includes two Ph1 studies as monotherapy and in combination with durvalumab or tremelimumab to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity in adults with selected advanced solid tumours. 

“Again, MEDI5062 remains an important asset in our broad immuno-oncology portfolio, and a promising component of our robust pipeline.”

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